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Evidence Zika Virus Can Cause Serious Complications GrowingEvidence virus can cause infant brain damage, a paralyzing neurological disorder ENLARGEA woman who is six months pregnant shows a photo of her ultrasound at the IMIP hospital in Brazil. The woman was struck with the Zika virus and was worried about the health of her baby, but her baby's ultrasound scan and other exams indicated everything was normal. PHOTO: ASSOCIATED PRESSBy BETSY MCKAYMarch 4, 2016 12:00 p.m. ET0 COMMENTSEvidence that Zika virus can cause complications such as infant brain damage and a paralyzing neurological disorder is growing stronger, with new research made public this week. In a series of lab experiments using stem cells, scientists showed the Zika virus infected cells that are critical for brain development, causing them to die or to stop functioning normally. The researchers said the findings shed new light on how Zika might disrupt brain development in the unborn child of an infected pregnant woman, possibly leading to a birth defect known as microcephaly in which children are born with undersized skulls and brains. The study was published Friday in the journal Cell Stem Cell. Separate research published in the journal The Lancet this weekconfirmed a link between Zika and Guillain-Barre Syndrome, a neurological disorder in which the immune system attacks the nervous system, causing temporary but sometimes severe paralysis. Brazil, Colombia and El Salvador have all reported an increase in the number of cases of the disorder as Zika has swept through their populations. The case-control study identified 42 patients who developed Guillain-Barre during an outbreak of Zika in French Polynesia in late 2013 and early 2014. All had Zika antibodies in their blood, compared with 56% of the members of a control group. Most weren’t severely affected; more than half could walk on their own three months after discharge from the hospital. But 12, or 29% of the group, required ventilators when paralysis affected their ability to breathe. Health officials say they are operating on the assumption that Zika is linked to these complications, while continuing research to determine the nature of the links and whether there are other factors involved. “There are numerous lines of evidence now that link microcephaly with Zika virus, so I don’t think there’s any question about that any longer,” Lyle Petersen, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention said in a briefing this week. In the latest study, researchers at Johns Hopkins University School of Medicine, Florida State University and Emory University exposed a strain of Zika to several types of cells, including “parental” cells that give rise to the neurons that form the brain. The virus infected and “hijacked” the parental cells, spawning more copies of the virus, said Guo-li Ming, an author and professor of neurology at Johns Hopkins. Many of the infected cells died. Others showed gene disruptions that made it impossible to generate new cells effectively, she said. “This is the first step toward understanding how Zika can affect brain development,” she said. The next step is to figure out how the virus damages the cells, said Hongjun Song, also an author and neurology professor at Johns Hopkins. Experts praised the research but said further work would need to be done to show how the lab findings apply to humans. “It’s a nice manuscript that I think is going to provide some information to help us understand how Zika virus might function and how it might impact fetal cells and the fetal brain,” said Catherine Y. Spong, acting director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. But, she said, “we need to know how this actually happens, and whether or not this is the mechanism that microcephaly is caused through.” Other questions that need to be answered include how the virus passes from the mother to the fetus, and what impact it can have at different stages of pregnancy, she said. The infection that the authors described doesn’t necessarily lead to microcephaly, said Amelia Pinto, an assistant professor of molecular microbiology and immunology at Saint Louis University, who studies immune responses to arboviruses such as West Nile virus and Zika. “West Nile can infect these cells and West Nile has never been known to cause microcephaly,” she said. Write to Betsy McKay at [email protected] http://www.wsj.com/articles/evidence-zika-virus-can-cause-serious-complications-growing-1457110802

Zika Infects Neural ProgenitorsScientists provide a potential biological link between Zika virus infection and microcephaly. By Ruth Williams | March 4, 2016 Zika virus (green) infects human neural progenitors and leads to cell death (red).SARAH C. OGDENLaboratory-grown human neural progenitor cells, which can give rise to the kind of neurons and glia found in the brain, can be infected and killed by a strain of Zika virus, according to a report published today (March 4) in Cell Stem Cell. The study, albeit preliminary, offers the first suggestion of how Zika infection of pregnant women might lead to microcephaly in their babies. “The study demonstrates that human neuron-like cells can be infected with Zika virus and that infection leads to death and reduced growth of the infected cells,” said microbiologist and immunologistAndrew Pekosz of Johns Hopkins University who was not involved in the study. “This is important because this may be a way to study the damage induced directly by infection.” The number of infants born with microcephaly—a neurological condition in which the brain and skull fail to grow at a normal pace—have risen dramatically in Brazil since late 2015. An outbreak of Zika virus infections in the country last year is strongly suspected to be the cause, but while the virus has been detected in the amniotic fluid of two babies and the brain tissue of one fetus with microcephaly, so far no causal link between the condition and the mosquito-borne pathogen has been made. Neurologist and neuroscientist Guo-li Ming of Johns Hopkins School of Medicine is an expert in human brain development and mental disorders. Because analyzing actual human brain development is practically impossible, she uses human neural progenitor cells derived from induced pluripotent stem cells (iPSCs) as a model system. On hearing about the Zika-microcephaly crisis in Brazil, Ming realized she had a unique opportunity to examine whether human neural progenitor cells might be susceptible to infection. Partnering with scientists at Florida State University who study Zika virus, Ming’s team inoculated the neural progenitors as well as human iPSCs, embryonic stem cells and immature neurons and compared the extent of the resulting infections. While less than 20 percent of the iPSCs, embryonic stem cells and neurons became infected, the infection of the neural progenitors was “really striking,” said Ming. Up to 90 percent of the cells contained the virus and “what is a bit scary to us,” she said, “is that we found these progenitor cells can actually spit out more virus”—with the potential to infect yet more progenitor cells. Ming and colleagues showed that infection of the progenitors either killed the cells or slowed their proliferation significantly. Neural progenitors “give rise to the larger population of neurons and glial cells of the brain,” Ming said. “So if they are infected and they die or have retarded growth we think that could have an impact on the neurons they will produce.” As yet, however, the team has no evidence for how such infection might affect brain development. “These laboratory findings may begin to unearth some possible mechanisms by which Zika virus infects and damages brain tissue,” said virologist Ian Mackay of the University of Queensland in Brisbane, Australia, who did not participate in the research. “But they are one step on a long path to understanding the mechanism in humans and should be considered with care and in context.” For one thing, he said, the virus strain used in the study differs to the one responsible for the ongoing outbreak in Latin America. “It is unclear whether this lab virus still behaves in the same way as do Zika viruses currently circulating in Brazilian mosquitoes and infected humans,” he said. Mackay added that the iPSC-derived neural cells grown in culture “may not yield infection results that accurately reflect disease processes in humans.” To gain a better understanding of potential disease mechanism, Ming’s team plans to examine whether the infected neural progenitor cells lead to abnormal development of brain organoids—cultured mini brainsderived from human iPSCs. “But still this won’t tell you directly if that’s what’s happening during pregnancies,” she said, “Ultimately, that evidence has to come from the clinic.” Indeed, agreed Mackay, “much work remains to be done to understand whether Zika virus is capable of causing the diseases or diagnoses with which it is being presumptively associated.” H. Tang et al., “Zika virus infects human cortical neural precursors and attenuates their growth,” Cell Stem Cell, doi:10.1016/j.stem.2016.02.016, 2016. TagsZika virus, virology, neuroscience, microcephaly, disease/medicine and cell & molecular biologyhttp://www.the-scientist.com/?articles.view/articleNo/45506/title/Zika-Infects-Neural-Progenitors/

e | Fri Mar 4, 2016 12:04pm ESTRelated: HEALTHStudy shows how Zika virus could cause fetal brain defectsNEW YORK | BY ANDREW M. SEAMAN left2 of 2rightLediane da Silva, who is eight months pregnant, is seen in the shanty town of Beco do Sururu, Recife, Brazil, January 29, 2016.REUTERS/UESLEI MARCELINOleft1 of 2right left2 of 2right left1 of 2rightThe Zika virus is capable of quickly infecting and harming developing fetal brain cells, scientists said on Friday in a study that provides insight into how the virus might cause the birth defect microcephaly in fetuses exposed in the womb. The researchers said their study, published in the journal Cell Stem Cell, does not provide proof of a direct causal link between Zika and microcephaly, but it does identify where the virus may be inflicting the most damage in developing fetuses. The mosquito-borne virus infects a kind of neural stem cell that goes on to form the cerebral cortex, the brain's outer layer responsible for intellectual capabilities and higher mental functions, the study showed. Researchers found that these cells, exposed to the virus in laboratory dishes, were infected within three days, turned into "virus factories" for viral replication and died more quickly than normal. "Our study shows once the virus gets to the brain it can reach these very important cells," researcher Hengli Tang, the study's lead author from Florida State University, said in an interview. Tang said the study suggests the virus would be capable of doing the damage seen in microcephaly, a condition defined by unusually small heads that can result in developmental problems. Zika has been linked to numerous cases of microcephaly in Brazil and is spreading rapidly in Latin America and Caribbean nations, prompting the World Health Organization to declare a global public health emergency. Much remains unknown about Zika, including whether the virus actually causes microcephaly. Brazil said it has confirmed more than 640 cases of microcephaly, and considers most of them to be related to Zika infections in the mothers. Brazil is investigating more than 4,200 additional suspected cases of microcephaly. "By determining whether Zika virus infects cells in the brain and what happens to a cell that is infected, this paper begins to tackle questions surrounding how a virus that had previously been known to cause a mild illness could be linked to microcephaly," Amelia Pinto, a Saint Louis University expert on viruses transmitted by arthropods such as mosquitoes and ticks, said in a statement. Tang said future studies will be needed to prove whether or not Zika causes microcephaly. "We know people would be interested in knowing this information, but a lot still needs to be done," Tang said. "Ultimately the proof would need to come from the clinical side and animal studies." The researchers are currently growing in the laboratory what they called "mini-brains" composed of the stem cells to see how the virus may affect development over a longer period of time. Traces of Zika virus have been found in the bodily fluids and tissue of mothers and babies affected by microcephaly. Dr. Lyle Petersen, director of the division of vector-borne diseases at the U.S. Centers for Disease Control and Prevention, told a news briefing on Wednesday at the Pan American Health Organization in Washington that there are numerous lines of evidence now linking Zika with microcephaly. "I don't think there is any question about that any longer," Petersen said. (Reporting by Andrew M. Seaman in New York; Additional reporting by Julie Steenhuysen in Chicago; Editing by Will Dunham) http://www.reuters.com/article/us-health-zika-brain-idUSKCN0W6249

A Zika breakthrough: Scientists detail how virus can attack fetal brain Resize Text Print Article Comments 5 Book mark article Read later list Saved to Reading List By Lena H. Sun and Brady Dennis March 4 at 12:48 PM U.S. researchers make breakthrough discovery on how Zika virus can cause rare birth defect Play Video2:36 U.S. researchers say they have discovered how the Zika virus can cause microcephaly, a rare birth defect in which babies are born with abnormally small heads and brain problems. (Florida State University)A team of U.S. researchers announced Friday that they believe they have discovered a mechanism for how the Zika virus can cause the rare birth defect known as microcephaly, in which babies are born with abnormally small heads and underdeveloped brains. Working with lab-grown human stem cells, scientists found that the virus selectively infected cells forming the brain's cortex, the thin outer layer of folded gray matter. Its assault made those cells more likely to die and less likely to divide normally and make new brain cells. The finding by researchers from Johns Hopkins University, Florida State University and Emory University offers among the strongest evidence yet of how Zika is harming fetuses. Health authorities are increasingly convinced that the mosquito-borne virus has caused microcephaly in hundreds of babies in Brazil, the epicenter of the Zika outbreak that is sweeping through the Americas. Get Zika news by email We will update you when news breaks about the virus. Sign up "It strengthens the case that Zika is a culprit behind microcephaly," said Joseph Gleeson, an investigator for the Howard Hughes Medical Institute, who was not involved in the study. "It's a very important piece in the puzzle." [In the U.S., 9 Zika pregnancies include 2 miscarriages and 1 baby with 'severe microcephaly'] Researchers have already documented an increase of microcephaly cases coinciding with the outbreak and have found evidence of the virus in brains of newborns who died, as well as in fluid from the placenta of infected pregnant women. Puerto Rico becoming a breeding ground for the Zika virus in the U.S.View PhotosCases of the virus are expected to rise on the island in coming months. And that raises the likelihood of transfer to the mainland.But one of the missing pieces has been information about how Zika can slow or halt brain development in an unborn child. While Friday's study doesn'tdefinitively prove that the disease causes microcephaly, it strengthens the link between the two by showing cells from the brain's cortex are vulnerable to attack from the virus, according Guo-li Ming, a Johns Hopkins neurologist and one of the lead authors. "What we show is the first piece of evidence" consistent with the hypothesis that Zika infections cause microcephaly, said Hengli Tang, a virologist at Florida State University and another lead author. "We're literally the first people in the world to know this, to know that this virus can infect these very important cells and interfere with their function." The study, published in the academic journal Cell Stem Cell, answers a key question about the viral path of attack, said Kristen Brennand, a stem cell biologist at the Icahn School of Medicine at Mount Sinai Medical Center in New York. The Zika virus, explained Play Video2:52 Everything you ever wanted to know about the Zika virus and its spread across North and South America. (Daron Taylor,Claritza Jimenez/The Washington Post)The researchers took human stem cells, exposed them to a strain of Zika and found that within three days, the virus had attacked specific kinds of cells critical to development of the brain's cortex. These cells became infected and also were hijacked to make new copies of the virus. Many died; others were damaged and unable to replicate. [Zika is expected to infect 1 in 5 Puerto Ricans, increasing threat to rest of U.S.] Researchers used the original Zika strain, first discovered in Uganda in 1947. That strain is 89 percent identical to the current strain that has spread rapidly to about three dozen countries and territories, primarily in the Americas. The authors and other experts noted that the study, which involved dozens of scientists working at four labs at three universities, still only goes so far and must be followed with additional research. It took place in a controlled environment, with lab-grown stem cells. Have you had an experience with Zika? We'd like to hear from you. But Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, said its findings offer "potentially important" new information about the link between Zika and microcephaly. "This paper points to a mechanism that's plausible and makes sense," Hotez said. "It gives us a clue as to why the virus inhibits the brain growth of a fetus. ... It adds an important brick in the wall that says Zika is the cause of this epidemic of microcephaly we're seeing. These kinds of studies can help melt away all the other theories." https://www.washingtonpost.com/news/to-your-health/wp/2016/03/04/a-zika-breakthrough-scientists-detail-how-virus-attacks-fetal-brain/

Zika virus kills developing brain cellsBy Gretchen VogelMar. 4, 2016 , 12:15 PM As fear of the Zika virus spreads nearly as quickly as the pathogen itself, two new laboratory studies offer the first solid evidence for how it could cause brain defects in babies: The virus appears to preferentially kill developing brain cells. The observation bolsters the growing case for a connection between the virus, which is spreading rapidly across Latin America, and an increase in the number of cases of microcephaly, a birth defect in which the brain fails to grow properly. The new work, done independently by two groups, shows that the virus readily infects neural stem cells—the precursors of neurons and other brain cells—whether they are grown on cell culture plates or coaxed to form 3D minibrains called cerebral organoids. The work “is going to be very important,” says Madeline Lancaster, a developmental biologist who studies human brain development at the Medical Research Council Laboratory of Molecular Biology in Cambridge, U.K. The results “are quite consistent with what you’re seeing in the babies with microcephaly.” Zika virus, named after a forest in Uganda where it was first isolated decades ago, usually causes only mild symptoms in people, including fever and rash. But after the virus started spreading across northeastern Brazil last year, doctors there noticed a striking increase in the number of babies born with microcephaly. Many of the mothers reported having symptoms consistent with Zika infection during their pregnancies. But it has been difficult to prove a link between the virus and the birth defects because blood tests for Zika virus are only accurate for about a week after infection. Nevertheless, circumstantial evidence has accumulated. Researchers have identified the virus in amniotic fluid of pregnant women whose fetuses were diagnosed with microcephaly and also in the brain tissue of a fetus diagnosed with the disorder. But because researchers had conducted scant research on the virus before this year, they had little data to suggest how the virus could cause such damage. To gauge the virus’s possible effects on the developing brain, researchers at Johns Hopkins University in Baltimore, Maryland, and Florida State University in Tallahassee used induced pluripotent stem (iPS) cells to grow, in lab dishes, immature brain cells called human cortical neural progenitor cells. (iPS cells are adult cells that have been reprogrammed into stem cells that can grow into most of the tissues in the body.) They then exposed the neural progenitor cells to a lab strain of Zika virus. The virus readily infected the neural stem cells, neuroscientists Hongjun Song and Guo-li Ming, virologist Hengli Tang, and their colleagues report today in Cell Stem Cell. Three days after the virus was applied, 85% of the cells in the culture dishes were infected. In contrast, when the virus was applied to cultures of fetal kidney cells, embryonic stem cells, and undifferentiated iPS cells, it infected fewer than 10% of the cells by day 3. Immature neurons derived from the neural progenitor cells were also less susceptible to the virus; 3 days after receiving a dose of the virus, fewer than 20% of those cells were infected. The researchers noticed that the infected progenitor cells were not killed right away. Instead, the virus “hijacked the cells,” using the cellular machinery to replicate themselves, Song says. That helped the virus to spread quickly through the cell population, he says. His team also reports that infected cells grew more slowly and had interrupted cell division cycles, which could also contribute to microcephaly. In a separate set of experiments, other researchers found that the virus can hamper the growth of another type of neural stem cell. In a preprint posted online on 2 March, neuroscientist Patricia Garcez and stem cell researcher Stevens Rehen at the D'Or Institute for Research and Education in Rio de Janiero, Brazil, report growing human iPS cells into clusters of neural stem cells called neurospheres, as well as into 3D organoids that in some ways resemble a miniature version of the human brain. When they infected the growing cells with Zika virus isolated from a Brazilian patient, the virus quickly killed most of the neurospheres and left the few survivors small and misshapen. Infected organoids grew to less than half their normal size. Lancaster says the results echo earlier studies of gene mutations that cause microcephaly, which also affect neural progenitor cells. “You have two very different causes of microcephaly, but you see something very similar happening: a depletion of neural stem cells, and that would lead to fewer neurons” in the developing brain, she says. Plenty of questions about the Zika virus and its apparent link to birth defects remain unanswered. Both Garcez and Song say they are now repeating their experiments with other viruses, including dengue, a virus closely related to Zika that is prevalent in the regions currently affected by the outbreak. (Some scientists suspect that previous exposure to other viruses could affect the outcome of Zika infections.) Researchers also still need to figure out how the virus crosses the placenta and infects the fetus directly, something most viruses can’t do. Posted in: HealthLatin AmericazikaDOI: 10.1126/science.aaf4148 Gretchen Vogelhttp://www.sciencemag.org/news/2016/03/zika-virus-kills-developing-brain-cells

Toward an Understanding of Zika's Neurological DangersNew research comes closer to connecting the virus with microcephaly and Guillain-Barré. JULIE BECK 12:00 PM ET HEALTHThe ubiquitous caveat in stories about the Zika virus thus far: Despite the huge uptick of cases in the birth defect microcephaly in Brazil, and despite the verrrrry suspicious correlation of this uptick with the arrival of Zika in the country, we don’t know for certain that Zika causes microcephaly. The same goes for the neurological disorder Guillain-Barré, cases of which have also climbed in time with the Zika outbreak. “More research is needed,” scientists and government officials have chorused, declaring a quest to get good science on the virus as quickly as possible. And it’s starting to show results. RELATED STORIESThe Past, Present, and Future of ZikaThe Link Between Zika and Climate ChangeThe Zika Virus's Family TreeA new study published Friday in Cell Stem Cell shows how Zika affects neural stem cells, which appear to be particularly vulnerable to the virus. This may be the mechanism by which Zika could cause microcephaly, a condition in which a baby is born with an unusually small head due to incomplete brain development. Researchers examined the effects of a strain of Zika virus (not the same strain currently circulating in the Americas, but the original strain, from Africa) on three different kinds of cells: induced pluripotent stem cells (stem cells with the potential to turn into any kind of cell in the body); human cortical neural progenitor cells, or NPCs (stem cells that are destined to become brain cells, specifically); and immature cortical neurons (young brain cells). They found that the Zika virus absolutely loves cortical neural progenitor cells. It just loves ‘em. Even with a relatively small viral load (one virus for every 10 cells), after three days, 65 to 90 percent of the brain stem cells were infected, meaning the cells were reproducing the virus. “These NPCs after infection, they become a viral factory,” says Guo-Li Ming, a professor of neurology at Johns Hopkins University and one of the study’s authors. In contrast, the infection rate in the pluripotent stem cells and the immature neural cells was pretty low—under 20 percent for each. As they’re making all these viruses, the NPCs’ growth and reproduction cycle is slowing down, and the cells are dying. Because a fetus’s nervous system is mostly developed by the second trimester, this research suggests that fetuses would be most at risk during the first trimester, when NPCs abound. Research has already shown that Zika can cross the placenta—the virus was found in the amniotic fluid of two Brazilian pregnant women whose fetuses were diagnosed with microcephaly. Once it does cross that barrier, it may target these brain stem cells, which could be what’s causing the condition. “After infection, the cells become a viral factory.”This week also saw research advancing the connection between Zika and Guillain-Barré: A study published in The Lancet on Monday offered the first real evidence that Zika can cause Guillain-Barré syndrome—an autoimmune disease in which the immune system targets a person’s nervous system. Guillain-Barré can completely paralyze people, to the point where they can’t breathe. Most people recover, though they may not fully regain their strength, according to the National Institutes of Health. The Lancet study looked at 42 patients who were diagnosed with Guillain-Barré at a Tahiti hospital during the 2013-2014 Zika outbreak in French Polynesia. Ninety-three percent of the Guillain-Barré patients had anti-Zika antibodies in their blood, and 88 percent of them reported that they’d had other Zika-esque symptoms within six days of the onset of their neurological symptoms. http://www.theatlantic.com/health/archive/2016/03/study-how-zika-could-cause-microcephaly/472149/

How the Zika virus is probably causing birth defects in children It may be changing how brain cells express genes By Loren Grush on March 4, 2016 12:11 pm @lorengrush (Mario Tama/Getty Images) Share on Facebook (15) Tweet Share (1) Pin (1)Strong evidence suggests the mosquito-borne Zika virus is causing infants to be born with birth defects — and a lab model provides clues on how it happens. The virus is capable of infecting the cells that form the brain's outer layer, making them more susceptible to death and preventing them from forming new tissue. Though this study took place in a lab dish, rather than in a human person, it may explain how Zika stunts brain development. THE VIRUS IS CAPABLE OF INFECTING THE CELLS THAT FORM THE BRAIN'S OUTER LAYER The findings come from a new study published in Cell Stem Cell that looked at how the Zika virus interacted with human stem cells grown in a lab. The stem cells were made to mimic the types of cells that eventually form the cortex — the brain's outer layer. Within three days of being exposed to Zika, up to 90 percent of these cells had been infected. Not only did this lead to massive cell death, but the infected cells were reprogrammed to produce even more copies of the Zika virus. These experiments could eventually help doctors find new drugs to stop the virus' damage on unborn babies, the study authors argue. The study is the first to show how Zika may be causing children to be born with abnormally small heads — a condition known as microcephaly. Researchers strongly suspect that the two conditions may be linked, due to the recent spread of both in Central and South America. Since March of last year, up to 1.5 million people in Brazil alone have been infected with the virus, according to the World Health Organization. The outbreak has coincided with a massive spike in cases of microcephaly in Brazil. Zika has also been found in the brains of developing fetuses, indicating that the virus can be transmitted from mother to child. Today's research still does not confirm that Zika is causing these birth defects. The researchers only looked at how the virus interacts with individual brain cells in a lab setting, indicating which cells may be susceptible to the virus. To truly confirm Zika is behind microcephaly, the researchers would need to observe how Zika damages the entire brain. "Maybe the next step will be to use Zika on a 3D mini-brain to look at a more direct link," said one of the study authors Zhexing Wen, a neurobiologist at Johns Hopkins University School of Medicine. This image shows cell death of the stem cells in red; the ZIKA virus is highlighted green. (Sarah C. Ogden) But the study did reveal the extent to which Zika may be damaging the developing brain's cells. When Zika was introduced into a plate of stem cells, the virus altered how the cells' genes were expressed, reprogramming the cells to become mini Zika-producing factories. The virus also seemed to turn off the genes needed to fight off viral infection, causing many of the stem cells to die. And the genes that govern cell division were disrupted as well, indicating that the cells couldn’t divide to form new brain tissue. http://www.theverge.com/2016/3/4/11161360/zika-virus-birth-defect-causes-fetus-brain-study THERE ARE STILL MANY UNKNOWNS ABOUT ZIKA'S ROLE ON THE DEVELOPING FETUS Even if these experiments don’t confirm a direct Zika-microcephaly link, they could be used to screen for drugs that stop Zika from harming the brain, according to Wen. Researchers could add different compounds to the stem cells when they are exposed to Zika, to see which drugs work best at preventing infection or cell death. Yet there are still many unknowns about Zika's role on the developing fetus that need to be answered, according to Sika Zheng, an assistant professor of biomedical sciences at University of California, Riverside, who was not involved in the study. It’s still unclear if Zika is harming the brain itself, or if it’s causing fevers and other symptoms in the mother that are indirectly damaging the baby's brain. And if Zika is directly harming the brain, how is it crossing the blood-brain barrier? "The single most important evidence is looking to see if this virus can get into the brain [in a living patient]," said Zheng.

Zika caught 'killing' brain cellsBy James GallagherHealth editor, BBC News website38 minutes ago From the sectionHealthImage copyrightGetty ImagesZika virusZika outbreak: What you need to knowZika outbreak: Travel adviceMothers' fears amid Zika outbreakVideo How mums-to-be are tackling ZikaZika virus kills the type of tissue found in the developing brain, researchers have shown. It was able to destroy or disrupt the growth of neural progenitor cells, which build the brain and nervous system, in lab tests. The discovery, published in the journal Cell Stem Cell, adds weight to claims that Zika is causing brain abnormalities in babies. However, the US researchers caution this is not yet the conclusive link. There have been more than 4,800 confirmed and suspected cases of babies born with small brains - microcephaly - in Brazil. It is widely thought that the Zika outbreak is to blame, but this has not been scientifically confirmed. The team from the Johns Hopkins, Florida State and Emory universities infected a range of tissue samples with Zika virus for two hours and then analysed the samples three days later. The virus was able to infect up to 90% of neural progenitor cells in a sample leading to nearly a third of cells dying and the growth of the rest being disrupted. A similar effect in a developing brain could have devastating results. Image copyrightFiocruzImage captionOne of the first images of the Zika virus taken from a patient in the outbreak in South AmericaThe virus was able to infect only 10% of other tissue types tested including more advanced brain cells, kidney cells and embryonic stem cells. Prof Guo-li Ming, one of the researchers, said the findings were significant and represented a first step to understanding the link between microcephaly and Zika. She told the BBC News website: "Neural progenitor cells are especially vulnerable to the Zika virus. "They are giving rise to the cortex - the primary part [of the brain] that shows reduced volume in microcephaly. "But this research does not provide the direct evidence that Zika virus is the cause for microcephaly." She said studies looking at brain organoids or animal studies were still needed. AnalysisDavid Shukman, Science editor, BBC News In the overcrowded hospitals of Recife, the teeming Brazilian city at the epicentre of the crisis, medics have long assumed that the Zika virus is to blame. In a sweltering waiting room last month, where anxious mothers were clutching babies with abnormally small heads, Dr Angela Rocha told me that she was convinced of the link. In a normal year, she said, she might see five suspected cases of microcephaly while in the previous few months she had seen more than 200. When I asked whether it would be wise to wait for a full scientific analysis with peer-reviewed conclusions, she looked at me with scorn. With so many cases, and more in prospect after the next rainy season, we do not have time to wait, she said. It is unclear why these cells should be so vulnerable, but it appears they do not mount an immune response to Zika infection. While not definitive, the study adds to mounting evidence including Zika being discovered in the brains of dead babies as well as in amniotic fluid. Brain development researcher Dr Madeline Lancaster, from the MRC Laboratory of Molecular Biology, said the study was a "significant step forward". She told the BBC News website: "The effect they see could well explain the surge in microcephaly and it opens the door for many further studies into how the virus is affecting stem cells and whether this affects their ability to generate neurons in the developing brain. "I think it's a very important contribution and is extremely timely." But she agreed with the researchers that more research was needed to "test whether Zika does indeed affect neuron generation and brain size" as well as how it crosses the placenta. Dr Bruce Aylward, from the World Health Organization, said the evidence was mounting that Zika was causing microcephaly and another condition - Guillain-Barre syndrome. He said: "Since the public health emergency of international concern was declared back in February, the evidence that there may be a causal relationship has continued to accumulate http://www.bbc.com/news/health-35725744

AUTHOR: SARAH ZHANG.SARAH ZHANG SCIENCE DATE OF PUBLICATION: 03.04.16.03.04.16 TIME OF PUBLICATION: 12:01 PM.12:01 PMLAB-GROWN BRAIN BALLS STRENGTHEN ZIKA’S LINK TO MICROCEPHALYClick to Open Overlay Gallery GETTY IMAGESTHE SUSPECTED LINK between Zika and microcephaly is looking stronger and stronger. At first, you may recall, the link was pure correlation: Brazil saw a huge uptick this fall in cases of microcephaly, a condition where babies are born with brains that are too small, at the same time Zika spread through the country. In the past few months, scientists have found the virus in the placenta, amniotic fluid, and—most tellingly—brain tissue of microcephalic fetuses. Now two new papers show that Zika kills developing brain tissue culture in a dish. Those results don’t completely solidify the link between the virus and birth defects, but public health officials aren’t taking any chances. “The association is strong enough that we need to assume that it is true until we show that it’s not,” says Amelia Pinto, an immunologist at St. Louis University, who was not involved in either study. In one paper, a team based at the Federal University of Rio Janeiro grew neural stem cells into tiny little balls of brain tissue called cerebral organoids. These aren’t as complex as full brains, but they give scientists a window into brain development, namely how an undifferentiated mass of stem cells turns into the different tissues of the brain. And with Zika, it didn’t look good. In the eleven days after the organoids were infected with Zika, they grew 40 percent less than the healthy ones. The paper was uploaded to the preprint archive PeerJ, though it has not been peer reviewed or published in a journal yet. In a second paper published today in the journal Cell Stem Cell, a Johns Hopkins University group didn’t grow brain balls. Instead, they took stem cells and turned them into a specific type of human neural progenitor cells, which are the precursor to cortical neurons. They found that these neural progenitor cells were especially vulnerable to Zika. The virus had marginal effects on the cells they grew from (stem cells) or the cells they grew into (cortical neurons), but it killed nearly a third of the human neural progenitor cells. What’s going on with the neural progenitor cells? Zika infection seemed to scramble normal gene expression in those cells, tamping down genes that help them grow into neurons and turning on genes for cell death. The group is now continuing this work in cerebral organoids says Guo-Li Ming, a neuroscientist at Johns Hopkins who led this study. As with any cell culture experiment, these papers have limitations. One caveat is the type of stem cells both groups used. They started with fully fledged adult cells that were “backwards aged” into stem cells and then chemically coaxed into neural stem cells. That’s not how brains develop in fetuses. But using actual human fetal brain tissue is very difficult. (See the whole controversy over Planned Parenthood’s role in providing fetal tissue last year.) More obviously, though, cells in a dish are not developing fetuses. Scientists hope to use animal models to piece together the complete story. Pinto is one of multiple researchers now using immunocompromised mice as a model for Zika infection. She’s especially interested in how the immune system’s inflammatory response to the virus may also might play a role in the brain defects. The story might get more complicated before it gets untangled. http://www.wired.com/2016/03/lab-grown-brain-balls-strengthen-zikas-link-microcephaly/

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Zika virus (ZIKV), a mosquito-borne flavivirus, is now reported to be circulating in 26 countries and territories in Latin America and the Caribbean (Petersen et al., 2016). While infected individuals can often be asymptomatic or have only mild symptoms, of mounting concern are reports linking ZIKV infection to fetal and newborn microcephaly and serious neurological complications, such as Guillain-Barré syndrome (Petersen et al., 2016). The World Health Organization declared a Public Health Emergency of International Concern on February 1 of 2016 (Heymann et al., 2016). ZIKV infects human skin cells, consistent with its major transmission route (Hamel et al., 2015). ZIKV was detected in the amniotic fluid of two pregnant women whose fetuses had been diagnosed with microcephaly (Calvet et al., 2016), suggesting that ZIKV can cross the placental barrier. ZIKV was also found in microcephalic fetal brain tissue (Mlakar et al., 2016). Because so little is known about direct cell targets and mechanisms of ZIKV, and because access to fetal human brain tissue is limited, there is an urgent need to develop a new strategy to determine whether there is a causal relationship between ZIKV infection and microcephaly. Here we used human induced pluripotent stem cells (hiPSCs) as an in vitro model to investigate whether ZIKV directly infects human neural cells and the nature of its impact. We obtained a ZIKV stock from the infected rhesus Macaca cell line LLC-MK2. We passaged the virus in the mosquito C6/C36 cell line and titered collected ZIKV on Vero cells, an interferon-deficient monkey cell line commonly used to titer viruses. Sequences of multiple RT-PCR fragments generated from this stock (Figure S1A) matched the sequence of MR766, the original ZIKV strain that likely passed from an infected rhesus monkey to mosquitos (Dick et al., 1952). We first tested several human cell lines and found varying levels of susceptibility to ZIKV infection (Table S1). Notably, the human embryonic kidney cell line HEK293T showed low permissiveness for ZIKV infection (Figure S1C). To identify direct target cells of ZIKV in the human neural lineage, we used a highly efficient protocol to differentiate hiPSCs into forebrain-specific human neural progenitor cells (hNPCs), which can be further differentiated into cortical neurons (Wen et al., 2014). The titer of ZIKV in the infected humans is currently unknown. We performed infections at a low multiplicity of infection (MOI < 0.1) and the medium containing virus inoculum was removed after a 2 hr incubation period. Infection rates were then quantified 56 hr later with RT-PCR using MR766-specific primers (Figure S1A) and with immunocytochemistry using an anti-ZIKV envelope antibody (Figures 1A and 1B ). The hNPCs were readily infected by ZIKV in vitro, with the infection spreading to 65%–90% of the cells within 3 days of inoculation (Figures 1A and 1C). Quantitative analysis showed similar results for hNPCs derived from hiPSC lines of two different subjects (Figure 1C). As a control, we also exposed human embryonic stem cells (hESCs), hiPSCs, and immature cortical neurons to ZIKV under the same conditions. hESCs and hiPSCs could also be infected by ZIKV, but the infection was limited to a few cells at the colony edge with reduced expression of the pluripotent marker NANOG (Figures 1C and S1D; Table S1). Immature neurons differentiated from hNPCs also exhibited lower levels of infection under our conditions (Figures 1B and 1C). Together, these results establish that hNPCs, a constitutive population of the developing embryonic brain, are a direct cell target of ZIKV. ZIKV envelope immunostaining exhibited the characteristic intracellular “virus factory” pattern of flaviviruses (Romero-Brey and Bartenschlager, 2014) (Figure 1A). We therefore tested infectivity using supernatant from infected hNPCs and observed robust infection of Vero cells (Figure 1D), indicating that productive infection of hNPCs leads to efficient secretion of infectious ZIKV particles. We next determined the potential impact of ZIKV infection on hNPCs. We found a 29.9% ± 6.6% reduction in the total number of viable cells 66–72 hr after ZIKV infection, as compared to the mock infection (n = 3). Interestingly, ZIKV infection led to significantly higher caspase-3 activation in hNPCs 3 days after infection, as compared to the mock infection, suggesting increased cell death (Figures 2A and 2B ). Furthermore, analysis of DNA content by flow cytometry suggested cell-cycle perturbation of infected hNPCs (Figures 2C and S2A). Therefore, ZIKV infection of hNPCs leads to attenuated growth of this cell population that is due, at least partly, to both increased cell death and cell-cycle dysregulation. To investigate the impact of ZIKV infection on hNPCs at the molecular level, we employed global transcriptome analyses (RNA-seq). Our genome-wide analyses identified a large number of differentially expressed genes upon viral infection (Figure S2B and Table S2). Gene Ontology analyses revealed a particular enrichment of downregulated genes in cell-cycle-related pathways (Figure 2D), which is consistent with our flow cytometry findings (Figure 2C). Upregulated genes were primarily enriched in transcription, protein transport, and catabolic processes (Figure 2E). Consistent with increased caspase-3 activation observed by immunocytochemistry (Figures 2A and 2B), RNA-seq analysis revealed upregulation of genes, including caspase-3, involved in the regulation of the apoptotic pathway (Figure 2E). These global transcriptome datasets not only support our cell biology findings but also provide a valuable resource for the field. It is not known whether specific strains of ZIKV circulating in geographically diverse parts of the world differ in their ability to impact neural development, and the stain we used had been discovered prior to the current reports of a potential epidemiologic link between ZIKV and microcephaly. Nevertheless, our results clearly demonstrate that ZIKV can directly infect hNPCs in vitro with high efficiency and that infection of hNPCs leads to attenuated population growth through virally induced caspase-3-mediated apoptosis and cell-cycle dysregulation. Infected hNPCs also release infectious viral particles, which presents a significant clinical challenge for developing effective therapeutics to arrest or block the impact of infection. Future studies using the hiPSC/hNPC model can determine whether various ZIKV strains impact hNPCs differently and, conversely, whether a single ZIKV strain differentially affects hNPCs from hiPSCs of various human populations. Flaviviruses tend to have broad cellular tropisms and multiple factors contribute to pathogenic outcomes, including specific cellular response and tissue accessibility. Dengue virus infects cells of several lineages and hematopoietic cells play an essential role in the associated pathogenesis (Pham et al., 2012). West Nile virus infects epithelial cells of multiple tissues and can be neuroinvasive (Suthar et al., 2013). We note that ZIKV also infects other human cell types, including skin cells and fibroblasts (Hamel et al., 2015), and it remains unknown how ZIKV may gain access to the fetal brain (Mlakar et al., 2016). The capacity of ZIKV to infect hNPCs and attenuate their growth underscores the urgent need for more research into the role of these cells in putative ZIKV-related neuropathology. The finding that ZIKV also infects immature neurons raises critical questions about pathological effects on neurons and other neural cell types in the brain, as well as potential long-term consequences. Intriguingly, an early animal study showed ZIKV infection of neurons and astrocytes in mice and observed enlarged astrocytes (Bell et al., 1971). Our study also raises the question of whether ZIKV infects neural stem cells in adult humans (Bond et al., 2015). In summary, our results fill a major gap in our knowledge about ZIKV biology and serve as an entry point to establish a mechanistic link between ZIKV and microcephaly. Our study also provides a tractable experimental system for modeling the impact of ZIKV on neural development and for investigating underlying cellular and molecular mechanisms. Of equal importance, our hNPC model and robust cellular phenotype comprise a readily scalable platform for high-throughput screens to prevent ZIKV infection of hNPCs and to ameliorate its pathological effects during neural development. Jump to SectionMain TextAuthor ContributionsAccession NumbersSupplemental InformationReferencesAuthor ContributionsH.T., H.S., and G.-l.M. conceived of the research, designed the study, and wrote the manuscript. C.H., S.C.O., Z.W., and X.Q. performed experiments, analyzed data, and contributed equally to this study. Y.L., B.Y., J.S., F.Z., and P.J. performed RNA-seq analysis, and E.M.L., K.M.C., and R.A.D. contributed to additional data collection. All authors commented on the manuscript. Jump to SectionMain TextAuthor ContributionsAccession NumbersSupplemental InformationReferencesAcknowledgmentsWe thank Yichen Cheng, Taylor Lee, and Jianshe Lang of the Tang laboratory, Lihong Liu and Yuan Cai of the Ming and Song laboratories, Luoxiu Huang of the Jin laboratory for technical assistance, Zhiheng Xu and additional laboratory members for suggestions, and Timothy Megraw for assistance with confocal imaging. H.T. thanks the College of Arts and Sciences and the Department of Biological Science at Florida State University for seed funding. This work was partially supported by NIH (AI119530/AI111250 to H.T., NS047344 to H.S., NS048271/NS095348 to G-l.M., and NS051630/NS079625/MH102690 to P.J.), MSCRF (to H.S.), and start-up funding (to H.S.). Jump to SectionMain TextAuthor ContributionsAccession NumbersSupplemental InformationReferencesAccession NumbersThe accession number for RNA-seq data reported in this paper is GEO:GSE78711. Jump to SectionMain TextAuthor ContributionsAccession NumbersSupplemental InformationReferencesSupplemental Information Document S1. Figures S1 and S2, Table S1, and Supplemental Experimental ProceduresTable S2. Differential Gene Expression between ZIKV-Infected and Mock-Infected hNPCs, Related to Figure 2(A) Sequencing information. (B) List of downregulated genes. (C) List of upregulated genes.

Hengli Tang11, Christy Hammack11, Sarah C. Ogden11, Zhexing Wen11, Xuyu Qian11, Yujing Li, Bing Yao, Jaehoon Shin,Feiran Zhang, Emily M. Lee, Kimberly M. Christian, Ruth A. Didier, Peng Jin, Hongjun Song, Guo-li Ming11Co-first authorPublication stage: In Press Corrected Proof DOI: http://dx.doi.org/10.1016/j.stem.2016.02.016 Article Info

Brief ReportSwitch to Standard View Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growthhttp://www.cell.com/cell-stem-cell/fulltext/S1934-5909(16)00106-5

Abstract Since the emergence of Zika virus (ZIKV), reports of microcephaly have increased dramatically in Brazil; however, causality between the widespread epidemic and malformations in fetal brains has not been confirmed. Here, we examine the effects of ZIKV infection in human neural stem cells growing as neurospheres and cerebral organoids. Using immunocytochemistry and electron microscopy, we show that ZIKV targets human brain cells, reducing their viability and growth as neurospheres and cerebral organoids. These results suggest that ZIKV abrogates neurogenesis during human brain development.

Patricia P Garcez1,2, Erick C Loiola2, Rodrigo F Madeiro da Costa2, Luiza Higa3, Pablo Trindade2, Rodrigo Delvecchio3, Juliana M Nascimento2,4, Rodrigo M Brindeiro3,Almicar Tanuri3, Stevens K Rehen1,2 1Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ,Brazil2D'Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ, Brazil3Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil4Department of Biochemistry and Tissue Biology / Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, BrazilDOI10.7287/peerj.preprints.1817v1Published2016-03-02Accepted2016-03-02Subject AreasCell Biology, Developmental Biology, NeuroscienceKeywordszika virus, cerebral organoids, cell death, microcephaly, stem cells

Zika virus impairs growth in human neurospheres and brain organoidshttps://peerj.com/preprints/1817/ Cell BiologyDevelopmental BiologyNeuroscience

Zika Virus – March 4, 2016 Texas has had 18 confirmed cases of Zika virus disease. 17 were in travelers who were infected abroad and diagnosed after they returned home. One case involved a Dallas County resident who had sexual contact with someone who acquired the Zika infection while traveling abroad. Case counts by county: Bexar – 3Dallas – 2Fort Bend – 1Harris – 9Tarrant – 1Travis - 2

New tool helps predict waves of babies with birth defects due to ZikaFELIPE DANA/AP By HELEN BRANSWELL @HelenBranswell MARCH 3, 2016 TwitterFacebookLinkedInEmailPrint Anew study may add weight to the coalescing belief that the Zika virus is most dangerous to a developing fetus in the first trimester and early in the second. The analysis, by scientists from the US Centers for Disease Control and Prevention, used data from a Zika outbreak in the northeastern Brazilian state of Bahia to determine when during pregnancy Zika-infected mothers who gave birth to children with abnormally small heads likely contracted the virus. The scientists also used the Bahia data to design a tool that will help other Zika-affected jurisdictions project when they might start to see babies born with microcephaly or other brain-related birth defects. A surge in births with these types of developmental problems will place a huge burden on public health services, so having a better sense of the timing is critical, said Dr. Christina Chambers, codirector of the Center for Promotion of Maternal Health and Infant Development at the University of California, San Diego. “To try to be able to make projections about when you would see these cases show up, I think, is really important,” said Chambers, who was not involved in the work. But she cautioned against assuming that the first and early second trimester are the only periods in which maternal infection can cause fetal defects. Read More: Everything you need to know about Zika virusThe fact that, to date, only Brazil has reported an increase in cases of microcephaly has led some to question whether Zika infection during pregnancy is truly linked to this birth defect. Health authorities in French Polynesia also reported a rise in cases of microcephaly after their Zika outbreak in 2013-2014, but the increase was only noted through a review of medical records undertaken when Brazil raised the alarm last fall. Some experts have suggested the lack of evidence from elsewhere is simply a matter of timing. Other countries in Latin America and the Caribbean only started to see Zika cases months after the virus arrived in Brazil, so women who were infected during pregnancy in those areas haven’t yet given birth. CDC The new paper from the CDC used the Bahia outbreak to draw up projections. If an outbreak began in a country last November, the authors said, babies who might have been infected in the womb would be born between April and September. Knowing when a Zika infection during pregnancy would be most dangerous to the fetus will permit public health officials to tailor their advice to pregnant women, said senior author Margaret Honein, an epidemiologist and cohead of the pregnancy and birth defects task force in the CDC’s Zika response. Honein also stressed the need to learn more about the full range of birth defects being seen among Brazilian babies whose mothers were infected during pregnancy. In recent weeks, it has become clear that microcephaly is just one birth defect among many that are being reported in newborns there. Helen Branswell can be reached at [email protected] Follow Helen on Twitter @HelenBranswell http://www.statnews.com/2016/03/03/tool-zika-babies-microcephaly/

A Mosquito Common In U.S. May Transmit Zika, Study FindsSHARE / COMMENTSMARCH 4, 2016 /by KATIE WORTH Tow Journalism Fellow, FRONTLINE/Columbia Journalism School Fellowships A culex mosquito pictured at the Arizona Department of Health Services laboratory in 2004. (Jeff Topping/Getty Images) One of the most common mosquitos in the United States may have the capacity to carry the Zika virus, according to preliminary research in Brazil. The findings, which have yet to be peer reviewed or confirmed outside of a lab, found that mosquitos from the family of mosquitos known as Culex may not only be infected with Zika, but could also reproduce the virus in their salivary glands — a key step for passing the virus to humans. If further research confirms the early results detected in 12 Culex mosquitos, many countries could be forced to radically rethink their mosquito control campaigns. In Brazil, those efforts have focused almost exclusively on eradicating a different kind of mosquito — the Aedis aegypti. The study was detailed by Constancia Ayres, a faculty member at the federal research institute Fiocruz Pernambuco in Recife, at a conference of scientists on Wednesday, and was greeted with both intrigue and caution. Dr. Idê Gurgel, a researcher at the institute, called the discovery “bombastic news” that could “change everything.” Sérgio Bessa Luz, director of the federal Fiocruz Amazônia research center in Manaus, cautioned that restraint was in order: “This is preliminary data,” he said. Even if the virus is in the saliva, “it’s not definitive” that it can transfer Zika effectively to humans, he said. “We can’t yet conclude [Culex is] a vector.” Scientists are still working to establish the most fundamental facts about the Zika virus. Although it has been known to researchers since 1947, the virus was considered a rare, obscure and non-threatening disease until last year, when hundreds of thousands of people in Brazil became infected. The virus usually has either no symptoms or mild ones — a rash, a low fever, swollen joints — but evidence has mounted that it can, in rare cases, attack the nervous system and cause debilitating problems, including a birth defect known as microcephaly in babies. But little research has focused on how Zika is transmitted. Ayres said a literature review only unearthed four studies from the last 70 years that investigated the disease’s potential vectors: They all focused on Aedes mosquitos. None considered the Culex species. Until now, the house-loving Aedes aegypti mosquito and its forest-dwelling cousin, Aedes albopictus, have been eyed as the likely culprits spreading the disease from Africa across Asia to the Americas. Those species are also believed to be the primary vectors for dengue and chikungunya, two other mosquito-borne viruses that have hounded Brazil. To Ayres, it seemed obvious to ask whether the Culex mosquito may also be carrying the disease: Culex quinquefasciatus, known in the U.S. as the southern common house mosquito, is even more common than Aedes aegypti in Brazil’s urban areas, she said. Both it and its close cousin, the Culex pipiens, are widespread throughout the U.S. and both can spread other diseases, such as West Nile virus and Japanese encephalitis. To explore their competence as a vector, Ayres fed 200 mosquitos — half Culex and half Aedes aegypti — with Zika-infected blood. She tested 12 of them and found that each had been infected with the disease after a week. She also tested the viral load in their salivary glands — an indication that the disease is being reproduced there and could transmit it through bites — and found the Culex mosquitos were reproducing it at an especially high level. Ayres will spend the next two weeks infecting and studying more mosquitos to confirm the results, she said. The next step will be to learn whether Culex are being infected with Zika in the wild. Ayres has enlisted mosquito abatement teams across two Brazilian states to send her all the mosquitos they collect during their home inspections. She has already begun receiving some, she said, and will receive thousands more in the coming months. Eventually her team will test them for Zika, dengue and chikungunya. Only then, she said, will she feel confident enough to postulate whether Culex mosquitos are indeed a major vector of Zika. The two mosquitos are radically different from each other: The Aedes feeds during the day; the Culex at dawn and dusk. Aedis likes fresh water; Culex likes dirty water. Aedes specializes in feeding on people; Culex prefers birds. Much attention has focused on Aedes aegypti because it is auniquely qualified vector for disease: A female can bite many people, which allows her to carry a disease from one person to the next. It likes urban and domestic environments, which means it is in close proximity to people. And the species specializes in human blood, which means it wastes no time biting other animals. The mosquitos’ territory extendsthroughout the planet’s tropical regions and is found in every city in Brazil. Culex mosquitos have an even broader territory than Aedes aegypti, and are common across Europe and the U.S. But they carry disease less efficiently than Aedes, because they tend to bite fewer humans in a row, limiting how many people they infect. Told by email about Ayres’ findings, Scott Weaver, scientific director of the Galveston National Laboratory, responded that he was “not completely surprised by these results.” But just because a mosquito can carry a disease does not decide whether it is “an important vector,” he said. “The main remaining question regarding Culex is how often they feed consecutively on humans, which is likely far less than (Aedes) aegypti,” he said. Ayres said that if Culex mosquitos prove to be a major vector, it would require an overhaul of mosquito control strategies: “The strategies that we are using to control Aedes aegypti are useless for Culex because they are completely different species,” she said. For instance, public education campaigns have urged people to wear repellent during the day — but if Culex is a vector, repellent would be sensible at night as well. Furthermore, Brazil would have to confront its major wastewater problems: In Recife, only about a third of homes are connected to the sewage system. Waste water from the rest drains into ditches, canals, or rivers, making an abundance of breeding grounds for Culex. The U.S. would also have to worry more about Zika if Culex proves to be a vector, said U.C. Davis professor Walter Leal, a partner in Ayres’s research. Aedes aegypti mosquitos are mostly confined to warmer states, such as Florida, Texas and parts of California, whereas Culex are found everywhere. “This is very bad luck for us in the U.S. if it proves correct,” said Leal. “In America we think, OK, this virus is coming, people are getting sick, but it’s OK because we don’t have so much Aedes aegypti. But we have a lot of Culex.” http://www.pbs.org/wgbh/frontline/article/a-mosquito-common-in-u-s-may-transmit-zika-study-finds/

Zika Virus InformationAs of March 3, 2016 there are no confirmed cases of Zika virus in South Carolina.

Map update https://www.google.com/maps/d/edit?hl=en&hl=en&authuser=0&authuser=0&mid=zv94AJqgUct4.kT4qLMXp3SLU

http://phpa.dhmh.maryland.gov/Pages/Zika.aspx Maryland Confirmed Zika Virus Infections (As of March 2, 2016) Travel-AssociatedLocally Acquired Vector-BorneTotal404

Maryland Confirmed Zika Virus Infections (As of March 2, 2016) Travel-AssociatedLocally Acquired Vector-BorneTotal404

Map update https://www.google.com/maps/d/edit?hl=en&hl=en&authuser=0&authuser=0&mid=zv94AJqgUct4.kT4qLMXp3SLU

The Illinois Department of Public Health is reporting 7 cases of Zika virus disease statewide. http://www.dph.illinois.gov/topics-services/diseases-and-conditions/zika