Evolutionary characterization of clades 126.96.36.199 H5N6 and 188.8.131.52c H5N1 HPAI viruses in Vietnam (2013–2019) revealed distinct reassortants from distant spillovers
Keywords:Avian influenza, reassortment, 184.108.40.206 H5N6 viruses, 220.127.116.11c H5N1 viruses, phylogenetic analysis, Vietnam
Highly pathogenic avian influenza (HPAI) H5Nx viruses have continually undergone multiple evolutionary dynamics for the generation of various clades, subclades, and genotypes where 18.104.22.168c, and 22.214.171.124 become predominant and co-circulating in Vietnam from 2014 to date. In this study, fifteen H5 sequences in our study and 90 from others from different clades, 0, 1, 1.1, 126.96.36.199a, 188.8.131.52c, 2.3.4, 184.108.40.206, 220.127.116.11, 18.104.22.168 and 22.214.171.124 of H5N1, H5N2, H5N6, were characterized for hemagglutinin (HA) properties, genetic and phylogenetic analyses. Blast searching using the dataset of the full length of two H5N6 viruses revealed one strain, e.g., A/Duck/Vietnam/HT7/2014(H5N6) in May 2014, belonging to the Sichuan 2014-lineage of Group D (Minor). The other strain, A/Chicken/Vietnam/NT3/2017(H5N6)/or CkNT3-2017 in the Spring of 2017, belonged to the Japanese-Korean late 2016-cluster of Group C (Major). This cluster possessed 140NHETS-145del stretch of Leucine/Serine deletion at position 145 in HA1 (S/L145del), distinct from all the 126.96.36.199 H5N6 viruses known to date. There has been no report of the similar CkNT3-2017 of 188.8.131.52 reassortant in Vietnam prior to our study. The migration flyway might be the route for transportation of this novel H5N6 virus from Japan to Vietnam. In addition, the topology revealed another novel subclade of H5N6 (2018–2019) possibly, of the Vietnamese internal reassortments. The “H5Nx” viruses in Vietnam, in fact, have continually undergone multiple evolutionary processes in parallel with those lineages in China and East-Asia. Variations at the key sites in HA and altered genetic characteristics in novel HPAI H5Nx viruses in Vietnam present a caution for the vaccination program and the risk for human infection.
Baek YG, Lee YN, Lee DH, Cheon SH, Kye SJ, Park YR, Si YJ, Lee MH, Lee YJ (2020) A novel reassortant clade 184.108.40.206 highly pathogenic avian influenza H5N6 virus identified in South Korea in 2018. Infect Genet Evol 78: 104056.
Bi Y, Chen Q, Wang Q, Chen J, Jin T, Wong G, Quan C, Liu J, Wu J, Yin R, Zhao L, Li M, Ding Z, Zou R, Xu W, Li H, Wang H, Tian K, Fu G, Huang Y, Shestopalov A, Li S, Xu B, Yu H, Luo T, Lu L, Xu X, Luo Y, Liu Y, Shi W, Liu D, Gao GF (2016). Genesis, Evolution and Prevalence of H5N6 Avian Influenza Viruses in China. Cell Host Microbe 20: 810–821.
Bi Y, Liu H, Xiong C, Liu D, Shi W, Li M, Liu S, Chen J, Chen G, Li Y, Yang G, Lei Y, Xiong Y, Lei F, Wang H, Chen Q, Chen J, Gao GF (2014) Novel avian influenza A (H5N6) viruses isolated in migratory waterfowl before the first human case reported in China. Sci Rep 6: 29888.
Chen LH, Lee DH, Liu YP, Li WC, Swayne DE, Chang JC, Chen YP, Lee F, Tu WJ, Lin YJ (2017) Reassortant Clade 220.127.116.11 of Highly Pathogenic Avian Influenza A(H5N6) Virus, Taiwan, 2017. Emerg Infect Dis 24(6): 1147–1149.
Chu DH, Okamatsu M, Matsuno K, Hiono T, Ogasawara K, Nguyen LT, Nguyen VL, Nguyen TN, Nguyen TT, Pham VD, Nguyen DH, Nguyen TD, To TL, Nguyen VH, Kida H, Sakoda Y (2016) Genetic and antigenic characterization of H5, H6 and H9 avian influenza viruses circulating in live bird markets with intervention in the center part of Vietnam. Vet Microbiol 192: 194–203.
Creanga A, Diep Thi N, Gerloff N, Hoa Thi D, Balish A, Hoang Dang N, Jang Y, Vui Thi D, Thor S, Jones J, Simpson N, Shu B, Emery S, Berman L, Nguyen HT, Bryant JE, Lindstrom S, Klimov A, Donis RO, Davis CT, Tung N (2013) Emergence of multiple clade 18.104.22.168 influenza A (H5N1) virus subgroups in Vietnam and detection of novel reassortants. Virology 444: 12–20.
Feng Y, Guan W, Yuan B, Wang Y, Li Z, Song Y, Li S, Yang Z, Zhong N, Zhang Y, Xia X (2016) Emergence of triple-subtype reassortants of fatal human H5N6 avian influenza virus in Yunnan, China. J Infect 72(6): 753–756.
Gao R, Gu M, Liu K, Li Q, Li J, Shi L, Li X, Wang X, Hu J, Liu X, Hu S, Chen S, Peng D, Jiao X, Liu X (2018) T160A mutation-induced deglycosylation at site 158 in hemagglutinin is a critical determinant of the dual receptor binding properties of clade 22.214.171.124 H5NX subtype avian influenza viruses. Vet Microbiol 217: 158–166.
King J, Schulze C, Engelhardt A, Hlinak A, Lennermann SL, Rigbers K, Skuballa J, Staubach C, Mettenleiter TC, Harder T, Beer M, Pohlmann A (2020) Novel HPAIV H5N8 Reassortant (Clade 126.96.36.199b) Detected in Germany. Viruses 12(3): pii:E281.
Mellor KC, Meyer A, Elkholly DA, Fournié G, Long PT, Inui K, Padungtod P, Gilbert M, Newman SH, Vergne T, Pfeiffer DU, Stevens KB (2018) Comparative epidemiology of highly pathogenic avian influenza virus H5N1 and H5N6 in Vietnamese live bird markets: Spatiotemporal patterns of distribution and risk factors. Front Vet Sci 5: 51.
Nguyen DT, Jang Y, Nguyen TD, Jones J, Shepard SS, Yang H, Gerloff N, Fabrizio T, Nguyen LV, Inui K, Yang G, Creanga A, Wang L, Mai DT, Thor S, Stevens J, To TL, Wentworth DE, Nguyen T, Pham DV, Bryant JE, Davis CT (2017) Shifting Clade Distribution, Reassortment, and Emergence of New Subtypes of Highly Pathogenic Avian Influenza A(H5) Viruses Collected from Vietnamese Poultry from 2012 to 2015. J Virol 91(5): pii: e01708-16.
Nguyen LT, Firestone SM, Stevenson MA, Young ND, Sims LD, Chu DH, Nguyen TN, Van Nguyen L, Thanh Le T, Van Nguyen H, Nguyen HN, Tien TN, Nguyen TD, Tran BN, Matsuno K, Okamatsu M, Kida H, Sakoda Y (2019a). A systematic study towards evolutionary and epidemiological dynamics of currently predominant H5 highly pathogenic avian influenza viruses in Vietnam. Sci Rep 9(1): 7723.
Nguyen LT, Stevenson MA, Firestone SM, Sims LD, Chu DH, Nguyen LV, Nguyen TN, Le KT, Isoda N, Matsuno K, Okamatsu M, Kida H, Sakoda Y (2019b) Spatiotemporal and risk analysis of H5 highly pathogenic avian influenza in Vietnam, 2014-2017. Prev Vet Med 22: 104678.
Nguyen TH, Than VT, Thanh HD, Nguyen VQ, Nguyen KH, Nguyen DT, Park JH, Chung IS, Jeong DG, Chang KT, Oh TK, Kim W (2015) The evolutionary dynamics of highly pathogenic avian influenza H5N1 in south-central Vietnam reveals multiple clades evolving from Chinese and Cambodian viruses. Comp Immunol Microbiol Infect Dis 42: 21–30.
Okamatsu M, Ozawa M, Soda K, Takakuwa H, Haga A, Hiono T, Matsuu A, Uchida Y, Iwata R, Matsuno K, Kuwahara M, Yabuta T, Usui T, Ito H, Onuma M, Sakoda Y, Saito T, Otsuki K, Ito T, Kida H (2017) Characterization of Highly Pathogenic Avian Influenza Virus A(H5N6), Japan, November 2016. Emerg Infect Dis 23(4): 691–695.
Pohlmann A, Hoffmann D, Grund C, Koethe S, Hüssy D, Meier SM, King J, Schinköthe J, Ulrich R, Harder T, Beer M (2019) Genetic Characterization and Zoonotic Potential of Highly Pathogenic Avian Influenza Virus A(H5N6/H5N5), Germany, 2017-2018. Emerg Infect Dis 25(10): 1973–1976.
Si Y, Lee IW, Kim E, Kim Y, Kwon H, Park S, Nguyen HD, Kim SM, Kwon J, Choi W, Beak YH, Song M, Kim C, Webby RJ, Choi Y (2017) Genetic characterisation of novel, highly pathogenic avian influenza (HPAI) H5N6 viruses isolated in birds, South Korea, November 2016. Euro Surveill 22(1): pii:30434.
Smith GJ, Donis RO, World Health Organization/World Organisation for Animal Health/Food and Agriculture Organization (WHO/OIE/FAO) H5 Evolution Working Group. 2015. Nomenclature updates resulting from the evolution of avian influenza A(H5) virus clades 188.8.131.52a, 2.2.1, and 2.3.4 during 2013–2014. Influenza Other Respir Viruses 9: 271–276.
Susloparov IM, Goncharova N, Kolosova N, Danilenko A, Marchenko V, Onkhonova G, Evseenko V, Gavrilova E, Maksutov RA, Ryzhikov A (2019) Genetic Characterization of Avian Influenza A(H5N6) Virus Clade 184.108.40.206, Russia, 2018. Emerg Infect Dis 25(12): 2338–2339.
Takemae N, Tsunekuni R, Sharshov K, Tanikawa T, Uchida Y, Ito H, Soda K, Usui T, Sobolev I, Shestopalov A, Yamaguchi T, Mine J, Ito T, Saito T (2017) Five distinct reassortants of H5N6 highly pathogenic avian influenza A viruses affected Japan during the winter of 2016-2017. Virology 512: 8–20.
Tsunekuni R, Sudo K, Nguyen PT, Luu BD, Phuong TD, Tan TM, Nguyen T, Mine J, Nakayama M, Tanikawa T, Sharshov K, Takemae N, Saito T (2019) Isolation of highly pathogenic H5N6 avian influenza virus in Southern Vietnam with genetic similarity to those infecting humans in China. Transbound Emerg Dis 66(6): 2209–2217.
Vergne T, Meyer A, Long PT, Elkholly DA, Inui K, Padungtod P, Newman SH, Fournié G, Pfeiffer DU (2019) Optimising the detectability of H5N1 and H5N6 highly pathogenic avian influenza viruses in Vietnamese live-bird markets. Sci Rep 9(1): 1031.
Yang L, Zhu W, Li X, Bo H, Zhang Y, Zou S, Gao R, Dong J, Zhao X, Chen W, Dong L, Zou X, Xing Y, Wang D, Shu Y (2017) Genesis and Dissemination of Highly Pathogenic H5N6 Avian Influenza Viruses. J Virol 91(5): pii: e02199-16.
Zhang J, Lao G, Zhang R, Wei Z, Wang H, Su G, Shan N, Li B, Li H, Yu Y, Jia W, Liao M, Qi W (2018) Genetic diversity and dissemination pathways of highly pathogenic H5N6 avian influenza viruses from birds in Southwestern China along the East Asian-Australian migration flyway. J Infect 76(4): 418–422.
Zhang T, Li R, Zhu G, Chang J, Xu B (2019) First Detection of a Novel Reassortant Avian Influenza A(H5N6) Clade 220.127.116.11c Virus, Isolated from a Wild Bird in China. Microbiol Resour Announc 8(36): pii: e00797-19.