niman Posted June 30, 2020 Report Posted June 30, 2020 Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity.
niman Posted June 30, 2020 Author Report Posted June 30, 2020 Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection Honglei Sun, Yihong Xiao, View ORCID ProfileJiyu Liu, Dayan Wang, Fangtao Li, Chenxi Wang, Chong Li, Junda Zhu, Jingwei Song, Haoran Sun, View ORCID ProfileZhimin Jiang, Litao Liu, Xin Zhang, Kai Wei, Dongjun Hou, Juan Pu, Yipeng Sun, Qi Tong, Yuhai Bi, Kin-Chow Chang, Sidang Liu, View ORCID ProfileGeorge F. Gao, and Jinhua Liu PNAS first published June 29, 2020 https://doi.org/10.1073/pnas.1921186117 Add to Cart ($10) Contributed by George F. Gao, April 28, 2020 (sent for review December 9, 2019; reviewed by Ian H. Brown and Xiu-Feng Henry Wan) https://www.pnas.org/content/early/2020/06/23/1921186117
niman Posted June 30, 2020 Author Report Posted June 30, 2020 Significance Pigs are intermediate hosts for the generation of pandemic influenza virus. Thus, systematic surveillance of influenza viruses in pigs is a key measure for prewarning the emergence of the next pandemic influenza. Here, we identified a reassortant EA H1N1 virus possessing pdm/09 and TR-derived internal genes, termed as G4 genotype, which has become predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses have all the essential hallmarks of a candidate pandemic virus. Of concern is that swine workers show elevated seroprevalence for G4 virus. Controlling the prevailing G4 EA H1N1 viruses in pigs and close monitoring in human populations, especially the workers in swine industry, should be urgently implemented.
niman Posted June 30, 2020 Author Report Posted June 30, 2020 Abstract Pigs are considered as important hosts or “mixing vessels” for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and preparedness for the next potential pandemic. Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China, and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells, and show efficient infectivity and aerosol transmission in ferrets. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses. Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses. swine influenza Eurasian avian-like H1N1 virus 2009 pandemic H1N1 virus reassortant pandemic potential Footnotes ↵1H.S., Y.X., and J.L. contributed equally to this work. ↵2To whom correspondence may be addressed. Email: [email protected] or [email protected]. Author contributions: Honglei Sun, Y.X., S.L., G.F.G., and Jinhua Liu designed research; Honglei Sun, Y.X., Jiyu Liu, F.L., C.L., J.Z., J.S., Haoran Sun, Z.J., L.L., X.Z., K.W., D.H., and Q.T. performed research; Honglei Sun, Jiyu Liu, D.W., C.W., J.P., Y.B., and Jinhua Liu analyzed data; and Honglei Sun, J.P., Y.S., K.-C.C., G.F.G., and Jinhua Liu wrote the paper. Reviewers: I.H.B., Animal and Plant Health Agency; and X.-F.H.W., University of Missouri.
niman Posted June 30, 2020 Author Report Posted June 30, 2020 (edited) Table S3. Accession numbers for new sequences generated in this study Strain name PB2 PB1 PA HA NP NA M NS A/swine/Beijing/496/2011(H1N1) MN416330 MN416417 MN416517 MN416590 MN418734 MN416694 MN418814 MN418660 A/swine/Beijing/592/2011(H1N1) MN416331 MN416418 MN416518 MN416591 MN418735 MN416695 MN418815 MN418661 A/swine/Beijing/82/2011(H1N1) MN416333 MN416420 MN416520 MN416593 MN418737 MN416697 MN418817 MN418663 A/swine/Beijing/957/2011(H1N1) MN416335 MN416422 MN416522 MN416595 MN418739 MN416699 MN418819 MN418665 A/swine/Hebei/102/2011(H1N1) MN416339 MN416426 MN416526 MN416599 MN418743 MN416703 MN418823 MN418669 A/swine/Hebei/19/2011(H1N1) MN416341 MN416428 MN416528 MN416601 MN418745 MN416705 MN418825 MN418671 A/swine/Hebei/36/2011(H1N1) MN416343 MN416430 MN416530 MN416603 MN418747 MN416707 MN418827 MN418673 A/swine/Henan/08/2011(H1N1) MN416350 MN416437 MN416537 MN416610 MN418754 MN416714 MN418834 MN418680 A/swine/Henan/15/2011(H1N1) MN416352 MN416439 MN416539 MN416612 MN418756 MN416716 MN418836 MN418682 A/swine/Henan/201/2011(H1N1) MN416354 MN416441 MN416541 MN416614 MN418758 MN416718 MN418838 MN418684 A/swine/Henan/202/2011(H1N1) MN416355 MN416442 MN416542 MN416615 MN418759 MN416719 MN418839 MN418685 A/swine/Henan/97/2011(H1N1) MN416358 MN416445 MN416545 MN416618 MN418762 MN416722 MN418842 MN418688 A/swine/Jiangsu/89/2011(H1N1) MN416363 MN416450 MN416550 MN416623 MN418767 MN416727 MN418847 MN418693 A/swine/Jilin/63/2011(H1N1) MN416371 MN416458 MN416558 MN416631 MN418775 MN416735 MN418855 MN418701 A/swine/Tianjin/137/2011(H1N1) MN416392 MN416479 MN416579 MN416652 MN418796 MN416756 MN418876 MN418722 A/swine/Beijing/731/2012(H1N1) MN416332 MN416419 MN416519 MN416592 MN418736 MN416696 MN418816 MN418662 A/swine/Beijing/951/2012(H1N1) MN416334 MN416421 MN416521 MN416594 MN418738 MN416698 MN418818 MN418664 A/swine/Hebei/156/2012(H1N1) MN416340 MN416427 MN416527 MN416600 MN418744 MN416704 MN418824 MN418670 A/swine/Hebei/350/2012(H1N1) MN416342 MN416429 MN416529 MN416602 MN418746 MN416706 MN418826 MN418672 A/swine/Hebei/535/2012(H1N1) MN416344 MN416431 MN416531 MN416604 MN418748 MN416708 MN418828 MN418674 A/swine/Hebei/561/2012(H1N1) MN416345 MN416432 MN416532 MN416605 MN418749 MN416709 MN418829 MN418675 A/swine/Henan/08/2012(H1N1) MN416351 MN416438 MN416538 MN416611 MN418755 MN416715 MN418835 MN418681 A/swine/Henan/20/2012(H1N1) MN416353 MN416440 MN416540 MN416613 MN418757 MN416717 MN418837 MN418683 A/swine/Henan/458/2012(H1N1) MN416356 MN416443 MN416543 MN416616 MN418760 MN416720 MN418840 MN418686 A/swine/Liaoning/408/2012(H1N1) MN416373 MN416460 MN416560 MN416633 MN418777 MN416737 MN418857 MN418703 A/swine/Liaoning/458/2012(H1N1) MN416374 MN416461 MN416561 MN416634 MN418778 MN416738 MN418858 MN418704 A/swine/Liaoning/590/2012(H1N1) MN416375 MN416462 MN416562 MN416635 MN418779 MN416739 MN418859 MN418705 A/swine/Liaoning/896/2012(H1N1) MN416376 MN416463 MN416563 MN416636 MN418780 MN416740 MN418860 MN418706 A/swine/Shandong/436/2012(H1N1) MN416387 MN416474 MN416574 MN416647 MN418791 MN416751 MN418871 MN418717 A/swine/Tianjin/741/2012(H1N1) MN416395 MN416482 MN416582 MN416655 MN418799 MN416759 MN418879 MN418725 A/swine/Tianjin/960/2012(H1N1) MN416398 MN416485 MN416585 MN416658 MN418802 MN416762 MN418882 MN418728 A/swine/Hebei/T37/2013(H1N1) MN416346 MN416433 MN416533 MN416606 MN418750 MN416710 MN418830 MN418676 A/swine/Henan/727/2013(H1N1) MN416357 MN416444 MN416544 MN416617 MN418761 MN416721 MN418841 MN418687 A/swine/Jilin/625/2013(H1N1) MN416370 MN416457 MN416557 MN416630 MN418774 MN416734 MN418854 MN418700 A/swine/Jilin/665/2013(H1N1) MN416372 MN416459 MN416559 MN416632 MN418776 MN416736 MN418856 MN418702 A/swine/Liaoning/950/2013(H1N1) MN416377 MN416464 MN416564 MN416637 MN418781 MN416741 MN418861 MN418707 A/swine/Liaoning/D66/2013(H1N1) MN416378 MN416465 MN416565 MN416638 MN418782 MN416742 MN418862 MN418708 A/swine/Shandong/39/2013(H1N1) MN416386 MN416473 MN416573 MN416646 MN418790 MN416750 MN418870 MN418716 A/swine/Shandong/862/2013(H1N1) MN416388 MN416475 MN416575 MN416648 MN418792 MN416752 MN418872 MN418718 A/swine/Tianjin/525/2013(H1N1) MN416394 MN416481 MN416581 MN416654 MN418798 MN416758 MN418878 MN418724 A/swine/Tianjin/9/2013(H1N1) MN416397 MN416484 MN416584 MN416657 MN418801 MN416761 MN418881 MN418727 A/swine/Shandong/S113/2014(H1N1) KP735701 KP735705 KP735709 KP735713 KP735717 KP735721 KP735725 KP735729 A/swine/Shandong/S153/2014(H1N1) KP735702 KP735706 KP735710 KP735714 KP735718 KP735722 KP735726 KP735730 A/swine/Shandong/S269/2014(H1N1) KP735703 KP735707 KP735711 KP735715 KP735719 KP735723 KP735727 KP735731 A/swine/Shandong/S93/2014(H1N1) KP735700 KP735704 KP735708 KP735712 KP735716 KP735720 KP735724 KP735728 A/swine/Anhui/1227/2015(H1N1) MN416328 MN416415 MN416515 MN416588 MN418732 MN416692 MN418812 MN418658 A/swine/Tianjin/158/2015(H1N1) MN416393 MN416480 MN416580 MN416653 MN418797 MN416757 MN418877 MN418723 A/swine/Tianjin/78/2015(H1N1) MN416396 MN416483 MN416583 MN416656 MN418800 MN416760 MN418880 MN418726 A/swine/Heilongjiang/1214/2016(H1N1) MN416349 MN416436 MN416536 MN416609 MN418753 MN416713 MN418833 MN418679 A/swine/Jilin/21/2016(H1N1) MN416367 MN416454 MN416554 MN416627 MN418771 MN416731 MN418851 MN418697 A/swine/Jilin/23/2016(H1N1) MN416368 MN416455 MN416555 MN416628 MN418772 MN416732 MN418852 MN418698 A/swine/Jilin/29/2016(H1N1) MN416369 MN416456 MN416556 MN416629 MN418773 MN416733 MN418853 MN418699 A/swine/Shandong/1203/2016(H1N1) MN416382 MN416469 MN416569 MN416642 MN418786 MN416746 MN418866 MN418712 A/swine/Shandong/1207/2016(H1N1) MN416383 MN416470 MN416570 MN416643 MN418787 MN416747 MN418867 MN418713 A/swine/Shandong/16/2016(H1N1) MN416384 MN416471 MN416571 MN416644 MN418788 MN416748 MN418868 MN418714 A/swine/Shandong/36/2016(H1N1) MN416385 MN416472 MN416572 MN416645 MN418789 MN416749 MN418869 MN418715 A/swine/Shandong/9/2016(H1N1) MN416389 MN416476 MN416576 MN416649 MN418793 MN416753 MN418873 MN418719 A/swine/Hebei/0113/2017(H1N1) MN416336 MN416423 MN416523 MN416596 MN418740 MN416700 MN418820 MN418666 A/swine/Hebei/0116/2017(H1N1) MN416337 MN416424 MN416524 MN416597 MN418741 MN416701 MN418821 MN418667 A/swine/Hebei/0221/2017(H1N1) MN416338 MN416425 MN416525 MN416598 MN418742 MN416702 MN418822 MN418668 A/swine/Heilongjiang/0110/2017(H1N1) MN416347 MN416434 MN416534 MN416607 MN418751 MN416711 MN418831 MN418677 A/swine/Heilongjiang/0140/2017(H1N1) MN416348 MN416435 MN416535 MN416608 MN418752 MN416712 MN418832 MN418678 A/swine/Shandong/0334/2017(H1N1) MN416379 MN416466 MN416566 MN416639 MN418783 MN416743 MN418863 MN418709 A/swine/Shandong/0336/2017(H1N1) MN416380 MN416467 MN416567 MN416640 MN418784 MN416744 MN418864 MN418710 A/swine/Shandong/0337/2017(H1N1) MN416381 MN416468 MN416568 MN416641 MN418785 MN416745 MN418865 MN418711 A/swine/Shandong/JM78/2017(H1N1) MN416390 MN416477 MN416577 MN416650 MN418794 MN416754 MN418874 MN418720 A/swine/Shandong/LY142/2017(H1N1) MN416391 MN416478 MN416578 MN416651 MN418795 MN416755 MN418875 MN418721 A/swine/Anhui/0202/2018(H1N1) MN416326 MN416413 MN416513 MN416586 MN418730 MN416690 MN418810 MN418656 A/swine/Anhui/0203/2018(H1N1) MN416327 MN416414 MN416514 MN416587 MN418731 MN416691 MN418811 MN418657 A/swine/Beijing/0301/2018(H1N1) MN416329 MN416416 MN416516 MN416589 MN418733 MN416693 MN418813 MN418659 A/swine/Henan/SN10/2018(H1N1) MN416359 MN416446 MN416546 MN416619 MN418763 MN416723 MN418843 MN418689 A/swine/Henan/SN11/2018(H1N1) MN416360 MN416447 MN416547 MN416620 MN418764 MN416724 MN418844 MN418690 A/swine/Henan/SN12/2018(H1N1) MN416361 MN416448 MN416548 MN416621 MN418765 MN416725 MN418845 MN418691 A/swine/Henan/SN13/2018(H1N1) MN416362 MN416449 MN416549 MN416622 MN418766 MN416726 MN418846 MN418692 A/swine/Jiangsu/J004/2018(H1N1) MN416364 MN416451 MN416551 MN416624 MN418768 MN416728 MN418848 MN418694 A/swine/Jiangsu/J005/2018(H1N1) MN416365 MN416452 MN416552 MN416625 MN418769 MN416729 MN418849 MN418695 A/swine/Jiangsu/J006/2018(H1N1) MN416366 MN416453 MN416553 MN416626 MN418770 MN416730 MN418850 MN418696 https://www.pnas.org/content/pnas/suppl/2020/06/23/1921186117.DCSupplemental/pnas.1921186117.sapp.pdf Edited June 30, 2020 by niman
niman Posted June 30, 2020 Author Report Posted June 30, 2020 Nasal swabs from more than 30,000 pigs in China over 7 years found an increase in an avianlike influenza virus that has swapped genes from several strains. HONGLEI SUN Swine flu strain with human pandemic potential increasingly found in pigs in China By Jon CohenJun. 29, 2020 , 3:00 PM What the world doesn’t need now is a pandemic on top of a pandemic. So a new finding that pigs in China are more and more frequently becoming infected with a strain of influenza that has the potential to jump to humans has infectious disease researchers worldwide taking serious notice. Robert Webster, an influenza investigator who recently retired from St. Jude Children’s Research Hospital, says it’s a “guessing game” as to whether this strain will mutate to readily transmit between humans, which it has not done yet. “We just do not know a pandemic is going to occur until the damn thing occurs,” Webster says, noting that China has the largest pig population in the world. “Will this one do it? God knows.” When multiple strains of influenza viruses infect the same pig, they can easily swap genes, a process known as “reassortment.” The new study, published today in the Proceedings of the National Academy of Sciences, focuses on an influenza virus dubbed G4. The virus is a unique blend of three lineages: one similar to strains found in European and Asian birds, the H1N1 strain that caused the 2009 pandemic, and a North American H1N1 that has genes from avian, human, and pig influenza viruses. The G4 variant is especially concerning because its core is an avian influenza virus—to which humans have no immunity—with bits of mammalian strains mixed in. “From the data presented, it appears that this is a swine influenza virus that is poised to emerge in humans,” says Edward Holmes, an evolutionary biologist at the University of Sydney who studies pathogens. “Clearly this situation needs to be monitored very closely.” As part of a project to identify potential pandemic influenza strains, a team led by Liu Jinhua from the China Agricultural University (CAU) analyzed nearly 30,000 nasal swabs taken from pigs at slaughterhouses in 10 Chinese provinces, and another 1000 swabs from pigs with respiratory symptoms seen at their school’s veterinary teaching hospital. The swabs, collected between 2011 and 2018, yielded 179 swine influenza viruses, the vast majority of which were G4 or one of five other G strains from the Eurasian avianlike lineage. “G4 virus has shown a sharp increase since 2016, and is the predominant genotype in circulation in pigs detected across at least 10 provinces,” they write. Sun Honglei, the paper’s first author, says G4’s inclusion of genes from the 2009 H1N1 pandemic “may promote the virus adaptation” that leads to human-to-human transmission. Therefore, “It’s necessary to strengthen the surveillance” of pigs in China for influenza viruses, says Sun, also at CAU. Influenza viruses frequently jump from pigs to humans, but most do not then transmit between humans. Two cases of G4 infections of humans have been documented and both were dead-end infections that did not transmit to other people. “The likelihood that this particular variant is going to cause a pandemic is low,” says Martha Nelson, an evolutionary biologist at the U.S. National Institutes of Health’s Fogarty International Center who studies pig influenza viruses in the United States and their spread to humans. But Nelson notes that no one knew about the pandemic H1N1 strain, which jumped from pigs to people, until the first human cases surfaced in 2009. “Influenza can surprise us,” Nelson says. “And there’s a risk that we neglect influenza and other threats at this time” of COVID-19. The new study offers but a tiny glimpse into swine influenza strains in China, which has 500 million pigs. While Nelson thinks the predominance of G4 in their analysis is an interesting finding, she says it’s hard to know whether its spread is a growing problem, given the relatively small sample size. “You’re really not getting a good snapshot of what is dominant in pigs in China,” she adds, stressing the need for more sampling in the nation's pigs. In the paper, Sun and colleagues—including George Gao, head of the Chinese Center for Disease Control and Prevention—describe lab dish studies that show how G4s have become adept at infecting and copying themselves in human airway epithelial cells. The viruses also readily infected and transmitted between ferrets, a popular animal model used to study human influenza. The researchers found antibodies to the G4 strain in 4.4% of 230 people studied in a household survey—and the rate more than doubled in swine workers. In addition to stepping up surveillance, Sun says it makes sense to develop a vaccine against G4 for both pigs and humans. Webster says at the very least, the seed stock to make a human vaccine—variants of a strain that grow rapidly in the eggs used to make a flu vaccine—should be produced now. “Making the seed stock is not a big deal, and we should have it ready,” Webster says. China rarely uses influenza vaccines in swine. Nelson says U.S. farms commonly do, but the vaccine has little effect because it’s often outdated and doesn’t match circulating strains. Ideally, Nelson says, we would produce a human G4 vaccine and have it in the stockpile, but that’s an involved process that requires substantial funding. “We need to be vigilant about other infectious disease threats even as COVID is going on because viruses have no interest in whether we’re already having another pandemic,” Nelson says.
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