Novel H5N8 PB2 Change D678F Raises Mammalian Adaptation Concerns

[niman]

National Veterinary Research Institut Poland has release H5N8 sequences (at GISAID) for all 8 gene segments from wild duck in West Pomeranian Voivodeship, A/wild duck/Poland/82A/2016.  Analysis of these sequences shows thta the isolate is a novel reassortant, which has 5 gene segments (H5, N8, MP, PB1, NS) matching the six sequences from five species infected by H5N8 at Uvs Lake in Russia (bordering Mongolia).  The other three gene segments (PB2, PA, NP) are most closely related various low path avian influenza sequences.

However, the PB2 sequence has a novel change at position 678 (D-->F).  A similar change at position 678 (D-->Y) has been found in H7N9 gain of function studies involving adaptation to transmission to contact ferrets, raising concerns that D678F may increase transmission of H5N8 to mammals.

Edited November 17, 2016 by niman

[niman]

 

Query 661 ATKRLTVLGKDAGALTEFPDEGTAGVESAVLRGFLILGKEDKRYGPALSINELSNLAKGE 720 AGT18829 661 .................Y.......................................... 720 AGK72311 661 .................G.......................................... 720 AGQ83723 661 .................D.......................................... 720 AMQ31291 661 .................D.......................................... 720 BAF76002 661 .................D.......................................... 720 ABI47980 661 .................D.......................................... 720 ALZ47763 661 .................D.......................................... 720 ABB87302 661 .................D.......................................... 720 ALP45756 661 .................D.......................................... 720 AJD10726 661 .................D.......................................... 720 AGR54673 661 .................D.......................................... 720 ADF65087 661 .................D.......................................... 720 ACZ45315 661 .................G.......................................... 720 AGL96967 661 .................D.......................................... 720 AGW43467 661 .................D.......................................... 720 AGQ83710 661 .................D.......................................... 720 AGB50872 661 .................D.......................................... 720 AFF26033 661 .................D.......................................... 720 ADQ26661 661 .................D.......................................... 720 ANT47337 661 .................D.......................................... 720 ANM72295 661 .................D.......................................... 720 AMK09517 661 .................D.......................................... 720 AMK48393 661 .................D.......................................... 720 ABR37428 661 .................D.......................................... 720 ALZ48285 661 .................D.......................................... 720 AJD09934 661 ......I..........D.......................................... 720 ACV90852 661 .................D.......................................... 720 ACI16707 661 .................D.......................................... 720 AGL96972 661 .................D.......................................... 720 AGL96942 661 .................D.......................................... 720 AGY42301 661 .................D.......................................... 720 AGQ83736 661 .................G.......................................... 720 AGK42360 661 .................D.......................................... 720 BAM42760 661 .................D.......................................... 720 AFJ12551 661 .................D.......................................... 720 ACR58996 661 .................D.......................................... 720 ACQ82832 661 .................D.......................................... 720 ABI94753 661 .................D.......................................... 720 ANO46286 661 .................D.......................................... 720 ANM72443 661 .................D.......................................... 720 ABO52114 661 .................D.......................................... 720 BAU50600 661 .................D.......................................... 720 BAU50564 661 .................D.......................................... 720 BAU50780 661 .................D.......................................... 720 ALZ47313 661 .................D.......................................... 720 ABB88120 661 .................D.......................................... 720 ABB88010 661 .................D.......................................... 720 ABB87527 661 .................D.......................................... 720 ALJ33415 661 .................D.......................................... 720 AJY53801 661 .................D.......................................... 720 AJJ93058 661 .................D.......................................... 720 AJD14458 661 .................D.......................................... 720 AJD14374 661 .................D.......................................... 720 AJD14038 661 .................D.......................................... 720 AHJ57329 661 .................D.......................................... 720 ACZ45342 661 .................D.......................................... 720 ACZ45334 661 .................D.......................................... 720 ACV90522 661 .................D.......................................... 720 ACM66707 661 .................D.......................................... 720 AHN04178 661 .................D.......................................... 720 AGY80568 661 .................D.......................................... 720 AGQ83759 661 .................D.......................................... 720 AGI41187 661 .................D.......................................... 720 AGL55198 661 .................D.......................................... 720 AGC73919 661 .................D.......................................... 720 AGB84850 661 .................D.......................................... 720 AGB51333 661 .................D.......................................... 720 AEM98344 661 .................D.......................................... 720 AFK75385 661 .................D.......................................... 720 AFJ13123 661 .................D.......................................... 720 AFF26044 661 .................D.......................................... 720 AFF25604 661 .................D.......................................... 720 AEM76009 661 .................D.......................................... 720 AEM75712 661 .................D.......................................... 720 AEM75463 661 .................D.......................................... 720 AEM75384 661 .................D.......................................... 720 AEM75282 661 .................D.......................................... 720 ADU20261 661 .................D.......I.................................. 720 ACU15192 661 .................D.......................................... 720 ACT84662 661 .................D.......................................... 720 ACT84185 661 .................D.......................................... 720 ABI84693 661 .................D.......................................... 720 AMD61714 661 .................D.......................................... 720 ANM72411 661 .................D.......................................... 720 ANE05627 661 .................D.......................................... 720 AMX73311 661 .................D.......................................... 720 AMQ46617 661 .................D.......................................... 720 AMQ32130 661 .................D.......................................... 720 AMQ29635 661 .................D.......................................... 720 AKZ42148 661 .................D.......................................... 720 ABS70448 661 .................D.......................................... 720 ABO52070 661 .................D.......................................... 720 ABO52015 661 .................D.......................................... 720 ABO51905 661 .................D.......................................... 720 BAU50876 661 .................D......................................V... 720 BAU50756 661 .................D.......................................... 720 ALZ47566 661 .................D.......................................... 720 ABB19935 661 ..............M..D.......................................... 720 AJD12805 661 .................D.......................................... 720 AJD09826 661 .................D.......................................... 720

[niman]

J Infect Dis. 2014 Feb 15;209(4):551-6. doi: 10.1093/infdis/jit474. Epub 2013 Aug 29.

Novel avian-origin human influenza A(H7N9) can be transmitted between ferrets via respiratory droplets.

Xu L¹, Bao L, Deng W, Dong L, Zhu H, Chen T, Lv Q, Li F, Yuan J, Xiang Z, Gao K, Xu Y, Huang L, Li Y, Liu J, Yao Y, Yu P, Li X, Huang W, Zhao X, Lan Y, Guo J, Yong W, Wei Q, Chen H, Zhang L, Qin C.

There were 4 mutations in the virus isolated from the contact ferret: D678Y in the gene encoding PB2 

https://www.ncbi.nlm.nih.gov/pubmed/23990570

[niman]

Trends Microbiol. 2014 Nov; 22(11): 623–631.

Published online 2014 Sep 25. doi:  10.1016/j.tim.2014.08.008

PMCID: PMC4252989

NIHMSID: NIHMS631460

Pandemic potential of H7N9 influenza viruses

Tokiko Watanabe,^1,2,3 Shinji Watanabe,^2,4 Eileen A. Maher,¹ Gabriele Neumann,¹ and Yoshihiro Kawaoka^1,2,3,5

Author information ► Copyright and License information ►

this transmissible virus also possessed a D678Y mutation in PB2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252989/#R103

[niman]

Supplementary Table 2.Amino acid substitutions identified inH7N9 virus derived from airborne contact ferret.

Virus	Amino acid residue at position No.
	PB2	HA	NP	NA
	678	148/157b	109	10
A/Anhui/1/2013a	D	R	I	T
Contact ferret derived A/Anhui/1/2013	Y	K	T	I

^aThe sequences of all eight viral genes were deposited in the influenza sequence database of the Global Initiative on Sharing All Influenza Data (GISAID) under accession No. of EPI439503 to EPI439510.

^bH7/H3 numbering.

http://jid.oxfordjournals.org/content/suppl/2013/08/23/jit474.DC1