Adaptation of H9N2 Influenza Viruses to Mammalian Hosts: A Review of Molecular Markers
Abstract
:1. Introduction
2. Risk Assessment of H9N2 Influenza Viruses
2.1. Emergence and Host Range of H9N2 Viruses
2.2. Genetic Diversity and Reassortment of H9N2 Viruses
2.3. Pathogenesis and Transmission of H9N2 Viruses in Mammals
3. Key Molecular Markers in H9N2 Influenza Viruses Associated with Host Adaptation
3.1. Hemagglutinin Protein
3.1.1. Receptor Binding
3.1.2. H9N2 Virus Stability and HA Activation
3.2. The H9N2 Polymerase Genes (PB2, PB1, PA)
3.2.1. Mammalian Adaptation Mutations in PB2
3.2.2. Mammalian Adaptation Mutations in PB1 and PA
4. Conclusions
Conflicts of Interest
References
- Verhagen, J.H.; Lexmond, P.; Vuong, O.; Schutten, M.; Guldemeester, J.; Osterhaus, A.D.; Elbers, A.R.; Slaterus, R.; Hornman, M.; Koch, G.; et al. Discordant detection of avian influenza virus subtypes in time and space between poultry and wild birds; Towards improvement of surveillance programs. PLoS ONE 2017, 12, e0173470. [Google Scholar] [CrossRef] [Green Version]
- Webster, R.G.; Bean, W.J.; Gorman, O.T.; Chambers, T.M.; Kawaoka, Y. Evolution and ecology of influenza A viruses. Microbiol. Rev. 1992, 56, 152–179. [Google Scholar] [CrossRef]
- Olsen, B.; Munster, V.J.; Wallensten, A.; Waldenstrom, J.; Osterhaus, A.D.; Fouchier, R.A. Global patterns of influenza a virus in wild birds. Science 2006, 312, 384–388. [Google Scholar] [CrossRef] [Green Version]
- Horimoto, T.; Kawaoka, Y. Pandemic threat posed by avian influenza A viruses. Clin. Microbiol. Rev. 2001, 14, 129–149. [Google Scholar] [CrossRef] [Green Version]
- Long, J.S.; Mistry, B.; Haslam, S.M.; Barclay, W.S. Host and viral determinants of influenza A virus species specificity. Nat. Rev. Microbiol. 2019, 17, 67–81. [Google Scholar] [CrossRef]
- Uyeki, T.M.; Katz, J.M.; Jernigan, D.B. Novel influenza A viruses and pandemic threats. Lancet 2017, 389, 2172–2174. [Google Scholar] [CrossRef]
- Taubenberger, J.K.; Morens, D.M. Pandemic influenza—Including a risk assessment of H5N1. Rev. Sci. Tech. 2009, 28, 187–202. [Google Scholar] [CrossRef] [Green Version]
- Jernigan, D.B.; Cox, N.J. H7N9: Preparing for the unexpected in influenza. Annu. Rev. Med. 2015, 66, 361–371. [Google Scholar] [CrossRef]
- Yiu Lai, K.; Wing Yiu Ng, G.; Fai Wong, K.; Fan Ngai Hung, I.; Kam Fai Hong, J.; Fan Cheng, F.; Kwok Cheung Chan, J. Human H7N9 avian influenza virus infection: A review and pandemic risk assessment. Emerg. Microbes Infect. 2013, 2, e48. [Google Scholar] [CrossRef]
- Homme, P.J.; Easterday, B.C. Avian influenza virus infections. I. Characteristics of influenza A-turkey-Wisconsin-1966 virus. Avian Dis. 1970, 14, 66–74. [Google Scholar] [CrossRef]
- Sharp, G.B.; Kawaoka, Y.; Jones, D.J.; Bean, W.J.; Pryor, S.P.; Hinshaw, V.; Webster, R.G. Coinfection of wild ducks by influenza A viruses: Distribution patterns and biological significance. J. Virol. 1997, 71, 6128–6135. [Google Scholar] [CrossRef] [Green Version]
- Jackwood, M.W.; Stallknecht, D.E. Molecular epidemiologic studies on North American H9 avian influenza virus isolates from waterfowl and shorebirds. Avian Dis. 2007, 51 (Suppl. 1), 448–450. [Google Scholar] [CrossRef]
- Alexander, D.J. An overview of the epidemiology of avian influenza. Vaccine 2007, 25, 5637–5644. [Google Scholar] [CrossRef]
- Cameron, K.R.; Gregory, V.; Banks, J.; Brown, I.H.; Alexander, D.J.; Hay, A.J.; Lin, Y.P. H9N2 subtype influenza A viruses in poultry in pakistan are closely related to the H9N2 viruses responsible for human infection in Hong Kong. Virology 2000, 278, 36–41. [Google Scholar] [CrossRef] [Green Version]
- Nili, H.; Asasi, K. Natural cases and an experimental study of H9N2 avian influenza in commercial broiler chickens of Iran. Avian Pathol. 2002, 31, 247–252. [Google Scholar] [CrossRef]
- Choi, Y.K.; Ozaki, H.; Webby, R.J.; Webster, R.G.; Peiris, J.S.; Poon, L.; Butt, C.; Leung, Y.H.; Guan, Y. Continuing evolution of H9N2 influenza viruses in Southeastern China. J. Virol. 2004, 78, 8609–8614. [Google Scholar] [CrossRef] [Green Version]
- Sun, X.; Xu, X.; Liu, Q.; Liang, D.; Li, C.; He, Q.; Jiang, J.; Cui, Y.; Li, J.; Zheng, L.; et al. Evidence of avian-like H9N2 influenza A virus among dogs in Guangxi, China. Infect. Genet. Evol. 2013, 20, 471–475. [Google Scholar] [CrossRef]
- Peiris, M.; Yuen, K.Y.; Leung, C.W.; Chan, K.H.; Ip, P.L.; Lai, R.W.; Orr, W.K.; Shortridge, K.F. Human infection with influenza H9N2. Lancet 1999, 354, 916–917. [Google Scholar] [CrossRef]
- Zhang, C.; Xuan, Y.; Shan, H.; Yang, H.; Wang, J.; Wang, K.; Li, G.; Qiao, J. Avian influenza virus H9N2 infections in farmed minks. Virol. J. 2015, 12, 180. [Google Scholar] [CrossRef] [Green Version]
- Yu, H.; Zhou, Y.J.; Li, G.X.; Ma, J.H.; Yan, L.P.; Wang, B.; Yang, F.R.; Huang, M.; Tong, G.Z. Genetic diversity of H9N2 influenza viruses from pigs in China: A potential threat to human health? Vet. Microbiol. 2011, 149, 254–261. [Google Scholar] [CrossRef]
- WHO Influenza at the Human-Animal Interface. Available online: https://www.who.int/influenza/human_animal_interface/Influenza_Summary_IRA_HA_interface_28_02_2020.pdf?ua=1 (accessed on 16 March 2020).
- Peacock, T.H.P.; James, J.; Sealy, J.E.; Iqbal, M. A Global Perspective on H9N2 Avian Influenza Virus. Viruses 2019, 11, 620. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, S.; Zhou, Y.; Song, W.; Pang, Q.; Miao, Z. Avian influenza virus H9N2 seroprevalence and risk factors for infection in occupational poultry-exposed workers in Tai’an of China. J. Med. Virol. 2016, 88, 1453–1456. [Google Scholar] [CrossRef]
- Wang, M.; Fu, C.X.; Zheng, B.J. Antibodies against H5 and H9 avian influenza among poultry workers in China. N. Engl. J. Med. 2009, 360, 2583–2584. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Tian, B.; Jianfang, Z.; Yongkun, C.; Xiaodan, L.; Wenfei, Z.; Yan, L.; Jing, T.; Junfeng, G.; Tao, C.; et al. A comprehensive retrospective study of the seroprevalence of H9N2 avian influenza viruses in occupationally exposed populations in China. PLoS ONE 2017, 12, e0178328. [Google Scholar] [CrossRef] [PubMed]
- Pusch, E.A.; Suarez, D.L. The Multifaceted Zoonotic Risk of H9N2 Avian Influenza. Vet. Sci. 2018, 5, 82. [Google Scholar] [CrossRef] [Green Version]
- Ahad, A.; Rabbani, M.; Yaqub, T.; Younus, M.; Mahmood, A.; Zubair, M.; Fatima, Z.; Khalid, R.K.; Rasheed, M. Serosurveillance to H9 and H7 avian influenza virus among poultry workers in Punjab Province, Pakistan. Pak. Vet. J. 2013, 33, 107–112. [Google Scholar]
- Li, C.; Wang, S.; Bing, G.; Carter, R.A.; Wang, Z.; Wang, J.; Wang, C.; Wang, L.; Wu, G.; Webster, R.G.; et al. Genetic evolution of influenza H9N2 viruses isolated from various hosts in China from 1994 to 2013. Emerg. Microbes Infect. 2017, 6, e106. [Google Scholar] [CrossRef] [Green Version]
- Gu, M.; Xu, L.; Wang, X.; Liu, X. Current situation of H9N2 subtype avian influenza in China. Vet. Res. 2017, 48, 49. [Google Scholar] [CrossRef] [Green Version]
- Li, K.S.; Xu, K.M.; Peiris, J.S.; Poon, L.L.; Yu, K.Z.; Yuen, K.Y.; Shortridge, K.F.; Webster, R.G.; Guan, Y. Characterization of H9 subtype influenza viruses from the ducks of southern China: A candidate for the next influenza pandemic in humans? J. Virol. 2003, 77, 6988–6994. [Google Scholar] [CrossRef] [Green Version]
- Peacock, T.P.; Benton, D.J.; Sadeyen, J.R.; Chang, P.; Sealy, J.E.; Bryant, J.E.; Martin, S.R.; Shelton, H.; McCauley, J.W.; Barclay, W.S. Variability in H9N2 haemagglutinin receptor-binding preference and the pH of fusion. Emerg. Microbes Infect. 2017, 6, e11. [Google Scholar] [CrossRef] [Green Version]
- Zhu, R.; Xu, D.; Yang, X.; Zhang, J.; Wang, S.; Shi, H.; Liu, X. Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014. PLoS ONE 2018, 13, e0199260. [Google Scholar] [CrossRef] [Green Version]
- Ye, G.; Liang, C.H.; Hua, D.G.; Song, L.Y.; Xiang, Y.G.; Guang, C.; Lan, C.H.; Ping, H.Y. Phylogenetic Analysis and Pathogenicity Assessment of Two Strains of Avian Influenza Virus Subtype H9N2 Isolated from Migratory Birds: High Homology of Internal Genes with Human H10N8 Virus. Front. Microbiol. 2016, 7, 57. [Google Scholar] [CrossRef] [Green Version]
- Cui, L.; Liu, D.; Shi, W.; Pan, J.; Qi, X.; Li, X.; Guo, X.; Zhou, M.; Li, W.; Li, J.; et al. Dynamic reassortments and genetic heterogeneity of the human-infecting influenza A (H7N9) virus. Nat. Commun. 2014, 5, 3142. [Google Scholar] [CrossRef] [Green Version]
- Shi, W.; Li, W.; Li, X.; Haywood, J.; Ma, J.; Gao, G.F.; Liu, D. Phylogenetics of varied subtypes of avian influenza viruses in China: Potential threat to humans. Protein Cell 2014, 5, 253–257. [Google Scholar] [CrossRef] [Green Version]
- Yang, L.; Zhu, W.; Li, X.; Bo, H.; Zhang, Y.; Zou, S.; Gao, R.; Dong, J.; Zhao, X.; Chen, W.; et al. Genesis and Dissemination of Highly Pathogenic H5N6 Avian Influenza Viruses. J. Virol. 2017, 91, 5. [Google Scholar] [CrossRef] [Green Version]
- Guan, Y.; Shortridge, K.F.; Krauss, S.; Webster, R.G. Molecular characterization of H9N2 influenza viruses: Were they the donors of the “internal” genes of H5N1 viruses in Hong Kong? Proc. Natl. Acad. Sci. USA 1999, 96, 9363–9367. [Google Scholar] [CrossRef] [Green Version]
- Li, X.; Shi, J.; Guo, J.; Deng, G.; Zhang, Q.; Wang, J.; He, X.; Wang, K.; Chen, J.; Li, Y.; et al. Genetics, receptor binding property, and transmissibility in mammals of naturally isolated H9N2 Avian Influenza viruses. PLoS Pathog. 2014, 10, e1004508. [Google Scholar] [CrossRef]
- The SJCEIRS H9 Working Group. Assessing the fitness of distinct clades of influenza A (H9N2) viruses. Emerg. Microbes Infect. 2013, 2, e75. [Google Scholar]
- Sang, X.; Wang, A.; Chai, T.; He, X.; Ding, J.; Gao, X.; Li, Y.; Zhang, K.; Ren, Z.; Li, L.; et al. Rapid emergence of a PB2-E627K substitution confers a virulent phenotype to an H9N2 avian influenza virus during adoption in mice. Arch. Virol. 2015, 160, 1267–1277. [Google Scholar] [CrossRef]
- Belser, J.A.; Katz, J.M.; Tumpey, T.M. The ferret as a model organism to study influenza A virus infection. Dis. Models Mech. 2011, 4, 575–579. [Google Scholar] [CrossRef] [Green Version]
- Lowen, A.C.; Bouvier, N.M.; Steel, J. Transmission in the guinea pig model. Curr. Top. Microbiol. Immunol. 2014, 385, 157–183. [Google Scholar]
- Wang, D.; Wang, J.; Bi, Y.; Fan, D.; Liu, H.; Luo, N.; Yang, Z.; Wang, S.; Chen, W.; Wang, J.; et al. Characterization of avian influenza H9N2 viruses isolated from ostriches (Struthio camelus). Sci. Rep. 2018, 8, 2273. [Google Scholar] [CrossRef] [Green Version]
- Lv, J.; Wei, B.; Yang, Y.; Yao, M.; Cai, Y.; Gao, Y.; Xia, X.; Zhao, X.; Liu, Z.; Li, X.; et al. Experimental transmission in guinea pigs of H9N2 avian influenza viruses from indoor air of chicken houses. Virus Res. 2012, 170, 102–108. [Google Scholar] [CrossRef]
- Sang, X.; Wang, A.; Ding, J.; Kong, H.; Gao, X.; Li, L.; Chai, T.; Li, Y.; Zhang, K.; Wang, C.; et al. Adaptation of H9N2 AIV in guinea pigs enables efficient transmission by direct contact and inefficient transmission by respiratory droplets. Sci. Rep. 2015, 5, 15928. [Google Scholar] [CrossRef] [Green Version]
- Hao, M.; Han, S.; Meng, D.; Li, R.; Lin, J.; Wang, M.; Zhou, T.; Chai, T. The PA Subunit of the Influenza Virus Polymerase Complex Affects Replication and Airborne Transmission of the H9N2 Subtype Avian Influenza Virus. Viruses 2019, 11, 40. [Google Scholar] [CrossRef] [Green Version]
- Wan, H.; Sorrell, E.M.; Song, H.; Hossain, M.J.; Ramirez-Nieto, G.; Monne, I.; Stevens, J.; Cattoli, G.; Capua, I.; Chen, L.M.; et al. Replication and transmission of H9N2 influenza viruses in ferrets: Evaluation of pandemic potential. PLoS ONE 2008, 3, e2923. [Google Scholar] [CrossRef] [Green Version]
- Sorrell, E.M.; Wan, H.; Araya, Y.; Song, H.; Perez, D.R. Minimal molecular constraints for respiratory droplet transmission of an avian-human H9N2 influenza A virus. Proc. Natl. Acad. Sci. USA 2009, 106, 7565–7570. [Google Scholar] [CrossRef] [Green Version]
- Kimble, J.B.; Sorrell, E.; Shao, H.; Martin, P.L.; Perez, D.R. Compatibility of H9N2 avian influenza surface genes and 2009 pandemic H1N1 internal genes for transmission in the ferret model. Proc. Natl. Acad. Sci. USA 2011, 108, 12084–12088. [Google Scholar] [CrossRef] [Green Version]
- Van Hoeven, N.; Pappas, C.; Belser, J.A.; Maines, T.R.; Zeng, H.; Garcia-Sastre, A.; Sasisekharan, R.; Katz, J.M.; Tumpey, T.M. Human HA and polymerase subunit PB2 proteins confer transmission of an avian influenza virus through the air. Proc. Natl. Acad. Sci. USA 2009, 106, 3366–3371. [Google Scholar] [CrossRef] [Green Version]
- Sun, X.; Whittaker, G.R. Entry of influenza virus. Adv. Exp. Med. Biol. 2013, 790, 72–82. [Google Scholar]
- Xiong, X.; McCauley, J.W.; Steinhauer, D.A. Receptor binding properties of the influenza virus hemagglutinin as a determinant of host range. Curr. Top. Microbiol. Immunol. 2014, 385, 63–91. [Google Scholar]
- Vines, A.; Wells, K.; Matrosovich, M.; Castrucci, M.R.; Ito, T.; Kawaoka, Y. The role of influenza A virus hemagglutinin residues 226 and 228 in receptor specificity and host range restriction. J. Virol. 1998, 72, 7626–7631. [Google Scholar] [CrossRef] [Green Version]
- Zou, S.; Zhang, Y.; Li, X.; Bo, H.; Wei, H.; Dong, L.; Yang, L.; Dong, J.; Liu, J.; Shu, Y.; et al. Molecular characterization and receptor binding specificity of H9N2 avian influenza viruses based on poultry-related environmental surveillance in China between 2013 and 2016. Virology 2019, 529, 135–143. [Google Scholar] [CrossRef]
- Srinivasan, K.; Raman, R.; Jayaraman, A.; Viswanathan, K.; Sasisekharan, R. Quantitative characterization of glycan-receptor binding of H9N2 influenza A virus hemagglutinin. PLoS ONE 2013, 8, e59550. [Google Scholar] [CrossRef]
- Matrosovich, M.N.; Krauss, S.; Webster, R.G. H9N2 influenza A viruses from poultry in Asia have human virus-like receptor specificity. Virology 2001, 281, 156–162. [Google Scholar] [CrossRef] [Green Version]
- Obadan, A.O.; Santos, J.; Ferreri, L.; Thompson, A.J.; Carnaccini, S.; Geiger, G.; Gonzalez Reiche, A.S.; Rajao, D.S.; Paulson, J.C.; Perez, D.R. Flexibility In Vitro of Amino Acid 226 in the Receptor-Binding Site of an H9 Subtype Influenza A Virus and Its Effect In Vivo on Virus Replication, Tropism, and Transmission. J. Virol. 2019, 93, e02011–e020118. [Google Scholar]
- Wan, H.; Perez, D.R. Amino acid 226 in the hemagglutinin of H9N2 influenza viruses determines cell tropism and replication in human airway epithelial cells. J. Virol. 2007, 81, 5181–5191. [Google Scholar] [CrossRef] [Green Version]
- Matrosovich, M.; Tuzikov, A.; Bovin, N.; Gambaryan, A.; Klimov, A.; Castrucci, M.R.; Donatelli, I.; Kawaoka, Y. Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. J. Virol. 2000, 74, 8502–8512. [Google Scholar] [CrossRef] [Green Version]
- Weis, W.; Brown, J.H.; Cusack, S.; Paulson, J.C.; Skehel, J.J.; Wiley, D.C. Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid. Nature 1988, 333, 426–431. [Google Scholar] [CrossRef]
- Teng, Q.; Xu, D.; Shen, W.; Liu, Q.; Rong, G.; Li, X.; Yan, L.; Yang, J.; Chen, H.; Yu, H.; et al. A Single Mutation at Position 190 in Hemagglutinin Enhances Binding Affinity for Human Type Sialic Acid Receptor and Replication of H9N2 Avian Influenza Virus in Mice. J. Virol. 2016, 90, 9806–9825. [Google Scholar] [CrossRef] [Green Version]
- Sealy, J.E.; Yaqub, T.; Peacock, T.P.; Chang, P.; Ermetal, B.; Clements, A.; Sadeyen, J.R.; Mehboob, A.; Shelton, H.; Bryant, J.E.; et al. Association of Increased Receptor-Binding Avidity of Influenza A(H9N2) Viruses with Escape from Antibody-Based Immunity and Enhanced Zoonotic Potential. Emerg. Infect. Dis. 2018, 25, 63–72. [Google Scholar] [CrossRef]
- Russier, M.; Yang, G.; Rehg, J.E.; Wong, S.S.; Mostafa, H.H.; Fabrizio, T.P.; Barman, S.; Krauss, S.; Webster, R.G.; Webby, R.J.; et al. Molecular requirements for a pandemic influenza virus: An acid-stable hemagglutinin protein. Proc. Natl. Acad. Sci. USA 2016, 113, 1636–1641. [Google Scholar] [CrossRef] [Green Version]
- Russell, C.J.; Hu, M.; Okda, F.A. Influenza Hemagglutinin Protein Stability, Activation, and Pandemic Risk. Trends Microbiol. 2018, 26, 841–853. [Google Scholar] [CrossRef]
- Di Lella, S.; Herrmann, A.; Mair, C.M. Modulation of the pH Stability of Influenza Virus Hemagglutinin: A Host Cell Adaptation Strategy. Biophys. J. 2016, 110, 2293–2301. [Google Scholar] [CrossRef] [Green Version]
- Herfst, S.; Schrauwen, E.J.; Linster, M.; Chutinimitkul, S.; de Wit, E.; Munster, V.J.; Sorrell, E.M.; Bestebroer, T.M.; Burke, D.F.; Smith, D.J.; et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science 2012, 336, 1534–1541. [Google Scholar] [CrossRef] [Green Version]
- Imai, M.; Watanabe, T.; Hatta, M.; Das, S.C.; Ozawa, M.; Shinya, K.; Zhong, G.; Hanson, A.; Katsura, H.; Watanabe, S.; et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 2012, 486, 420–428. [Google Scholar] [CrossRef] [Green Version]
- Zhong, L.; Wang, X.; Li, Q.; Liu, D.; Chen, H.; Zhao, M.; Gu, X.; He, L.; Liu, X.; Gu, M.; et al. Molecular mechanism of the airborne transmissibility of H9N2 avian influenza A viruses in chickens. J. Virol. 2014, 88, 9568–9578. [Google Scholar] [CrossRef] [Green Version]
- Cauldwell, A.V.; Long, J.S.; Moncorge, O.; Barclay, W.S. Viral determinants of influenza A virus host range. J. Gen. Virol. 2014, 95 Pt 6, 1193–1210. [Google Scholar] [CrossRef] [Green Version]
- Boivin, S.; Cusack, S.; Ruigrok, R.W.; Hart, D.J. Influenza A virus polymerase: Structural insights into replication and host adaptation mechanisms. J. Biol. Chem. 2010, 285, 28411–28417. [Google Scholar] [CrossRef] [Green Version]
- Subbarao, E.K.; Kawaoka, Y.; Murphy, B.R. Rescue of an influenza A virus wild-type PB2 gene and a mutant derivative bearing a site-specific temperature-sensitive and attenuating mutation. J. Virol. 1993, 67, 7223–7228. [Google Scholar] [CrossRef] [Green Version]
- Taubenberger, J.K.; Reid, A.H.; Lourens, R.M.; Wang, R.; Jin, G.; Fanning, T.G. Characterization of the 1918 influenza virus polymerase genes. Nature 2005, 437, 889–893. [Google Scholar] [CrossRef] [PubMed]
- Li, K.S.; Guan, Y.; Wang, J.; Smith, G.J.; Xu, K.M.; Duan, L.; Rahardjo, A.P.; Puthavathana, P.; Buranathai, C.; Nguyen, T.D.; et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 2004, 430, 209–213. [Google Scholar] [CrossRef] [PubMed]
- Wang, D.; Yang, L.; Gao, R.; Zhang, X.; Tan, Y.; Wu, A.; Zhu, W.; Zhou, J.; Zou, S.; Li, X.; et al. Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013. Eurosurveillance 2014, 19, 20836. [Google Scholar] [CrossRef] [Green Version]
- Luk, G.S.; Leung, C.Y.; Sia, S.F.; Choy, K.T.; Zhou, J.; Ho, C.C.; Cheung, P.P.; Lee, E.F.; Wai, C.K.; Li, P.C.; et al. Transmission of H7N9 Influenza Viruses with a Polymorphism at PB2 Residue 627 in Chickens and Ferrets. J. Virol. 2015, 89, 9939–9951. [Google Scholar] [CrossRef] [Green Version]
- Mehle, A.; Doudna, J.A. Adaptive strategies of the influenza virus polymerase for replication in humans. Proc. Natl. Acad. Sci. USA 2009, 106, 21312–21316. [Google Scholar] [CrossRef] [Green Version]
- Tarendeau, F.; Crepin, T.; Guilligay, D.; Ruigrok, R.W.; Cusack, S.; Hart, D.J. Host determinant residue lysine 627 lies on the surface of a discrete, folded domain of influenza virus polymerase PB2 subunit. PLoS Pathog. 2008, 4, e1000136. [Google Scholar] [CrossRef]
- Yamada, S.; Hatta, M.; Staker, B.L.; Watanabe, S.; Imai, M.; Shinya, K.; Sakai-Tagawa, Y.; Ito, M.; Ozawa, M.; Watanabe, T.; et al. Biological and structural characterization of a host-adapting amino acid in influenza virus. PLoS Pathog. 2010, 6, e1001034. [Google Scholar] [CrossRef] [Green Version]
- Gabriel, G.; Dauber, B.; Wolff, T.; Planz, O.; Klenk, H.D.; Stech, J. The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc. Natl. Acad. Sci. USA 2005, 102, 18590–18595. [Google Scholar] [CrossRef] [Green Version]
- Gao, Y.; Zhang, Y.; Shinya, K.; Deng, G.; Jiang, Y.; Li, Z.; Guan, Y.; Tian, G.; Li, Y.; Shi, J.; et al. Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host. PLoS Pathog. 2009, 5, e1000709. [Google Scholar] [CrossRef] [Green Version]
- Steel, J.; Lowen, A.C.; Mubareka, S.; Palese, P. Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N. PLoS Pathog. 2009, 5, e1000252. [Google Scholar] [CrossRef]
- Zhou, B.; Pearce, M.B.; Li, Y.; Wang, J.; Mason, R.J.; Tumpey, T.M.; Wentworth, D.E. Asparagine substitution at PB2 residue 701 enhances the replication, pathogenicity, and transmission of the 2009 pandemic H1N1 influenza A virus. PLoS ONE 2013, 8, e67616. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Finkelstein, D.B.; Mukatira, S.; Mehta, P.K.; Obenauer, J.C.; Su, X.; Webster, R.G.; Naeve, C.W. Persistent host markers in pandemic and H5N1 influenza viruses. J. Virol. 2007, 81, 10292–10299. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fan, S.; Hatta, M.; Kim, J.H.; Halfmann, P.; Imai, M.; Macken, C.A.; Le, M.Q.; Nguyen, T.; Neumann, G.; Kawaoka, Y. Novel residues in avian influenza virus PB2 protein affect virulence in mammalian hosts. Nat. Commun. 2014, 5, 5021. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, Z.; Yi, C.; Zhao, L.; Wang, S.; Zhou, L.; Hu, Y.; Zou, W.; Chen, H.; Jin, M. PB2-588I enhances 2009 H1N1 pandemic influenza virus virulence by increasing viral replication and exacerbating PB2 inhibition of beta interferon expression. J. Virol. 2014, 88, 2260–2267. [Google Scholar] [CrossRef] [Green Version]
- Xiao, C.; Ma, W.; Sun, N.; Huang, L.; Li, Y.; Zeng, Z.; Wen, Y.; Zhang, Z.; Li, H.; Li, Q.; et al. PB2–588 V promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses. Sci. Rep. 2016, 6, 19474. [Google Scholar] [CrossRef] [Green Version]
- Li, Y.; Qi, W.; Qiao, J.; Chen, C.; Liao, M.; Xiao, C. Evolving HA and PB2 genes of influenza A (H7N9) viruses in the fifth wave - Increasing threat to both birds and humans? J. Infect. 2017, 75, 184–186. [Google Scholar] [CrossRef]
- Song, W.; Wang, P.; Mok, B.W.; Lau, S.Y.; Huang, X.; Wu, W.L.; Zheng, M.; Wen, X.; Yang, S.; Chen, Y.; et al. The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication. Nat. Commun. 2014, 5, 5509. [Google Scholar] [CrossRef] [Green Version]
- Zhou, J.; Wang, D.; Gao, R.; Zhao, B.; Song, J.; Qi, X.; Zhang, Y.; Shi, Y.; Yang, L.; Zhu, W.; et al. Biological features of novel avian influenza A (H7N9) virus. Nature 2013, 499, 500–503. [Google Scholar] [CrossRef]
- Bussey, K.A.; Bousse, T.L.; Desmet, E.A.; Kim, B.; Takimoto, T. PB2 residue 271 plays a key role in enhanced polymerase activity of influenza A viruses in mammalian host cells. J. Virol. 2010, 84, 4395–4406. [Google Scholar] [CrossRef] [Green Version]
- Foeglein, A.; Loucaides, E.M.; Mura, M.; Wise, H.M.; Barclay, W.S.; Digard, P. Influence of PB2 host-range determinants on the intranuclear mobility of the influenza A virus polymerase. J. Gen. Virol. 2011, 92 Pt 7, 1650–1661. [Google Scholar] [CrossRef]
- Chen, G.W.; Chang, S.C.; Mok, C.K.; Lo, Y.L.; Kung, Y.N.; Huang, J.H.; Shih, Y.H.; Wang, J.Y.; Chiang, C.; Chen, C.J.; et al. Genomic signatures of human versus avian influenza A viruses. Emerg. Infect. Dis. 2006, 12, 1353–1360. [Google Scholar] [CrossRef]
- Guu, T.S.; Dong, L.; Wittung-Stafshede, P.; Tao, Y.J. Mapping the domain structure of the influenza A virus polymerase acidic protein (PA) and its interaction with the basic protein 1 (PB1) subunit. Virology 2008, 379, 135–142. [Google Scholar] [CrossRef]
- Kawaguchi, A.; Naito, T.; Nagata, K. Involvement of influenza virus PA subunit in assembly of functional RNA polymerase complexes. J. Virol. 2005, 79, 732–744. [Google Scholar] [CrossRef] [Green Version]
- Hu, J.; Hu, Z.; Song, Q.; Gu, M.; Liu, X.; Wang, X.; Hu, S.; Chen, C.; Liu, H.; Liu, W.; et al. The PA-gene-mediated lethal dissemination and excessive innate immune response contribute to the high virulence of H5N1 avian influenza virus in mice. J. Virol. 2013, 87, 2660–2672. [Google Scholar] [CrossRef] [Green Version]
- Xu, W.; Sun, Z.; Liu, Q.; Xu, J.; Jiang, S.; Lu, L. PA-356R is a unique signature of the avian influenza A (H7N9) viruses with bird-to-human transmissibility: Potential implication for animal surveillances. J. Infect. 2013, 67, 490–494. [Google Scholar] [CrossRef]
- Xu, G.; Zhang, X.; Gao, W.; Wang, C.; Wang, J.; Sun, H.; Sun, Y.; Guo, L.; Zhang, R.; Chang, K.C.; et al. Prevailing PA Mutation K356R in Avian Influenza H9N2 Virus Increases Mammalian Replication and Pathogenicity. J. Virol. 2016, 90, 8105–8114. [Google Scholar] [CrossRef] [Green Version]
- Bussey, K.A.; Desmet, E.A.; Mattiacio, J.L.; Hamilton, A.; Bradel-Tretheway, B.; Bussey, H.E.; Kim, B.; Dewhurst, S.; Takimoto, T. PA residues in the 2009 H1N1 pandemic influenza virus enhance avian influenza virus polymerase activity in mammalian cells. J. Virol. 2011, 85, 7020–7028. [Google Scholar] [CrossRef] [Green Version]
- CDC Influenza Risk Assessment Tool (IRAT). Available online: https://www.cdc.gov/flu/pandemic-resources/national-strategy/risk-assessment.htm (accessed on 15 March 2020).
- WHO Tool for Influenza Pandemic Risk Assessment (TIPRA). Available online: https://www.who.int/influenza/areas_of_work/human_animal_interface/tipra/en/ (accessed on 15 March 2020).
Location | % of H9N2 Viruses with the Amino Acid Shown | ||||||
---|---|---|---|---|---|---|---|
<1999 | 1999–2012 | 201–2019 | Avian Isolates | Human | Nonhuman Mammals | ||
HA | (n = 96)c | (n = 1367) | (n = 1212) | (n = 2675) | (n = 34) | (n = 35) | |
155T (145)a | 100 | 98.8 | 99.7 | 99.2 | 100 | 100 | |
183N (173)b | 34.4 | 64 | 73.2 | 67.1 | 76.5 | 85.7 | |
190T/V (180) | 22.9 | 38.4 | 57.2 | 56.3 | 61.8 | 60 | |
226L (216) | 14.6 | 72.1 | 95.1 | 80.4 | 85.7 | 57.1 | |
227Q (217) | 97.9 | 71.4 | 6.5 | 43.0 | 52.9 | 62.8 | |
228S (218) | 0 | 0 | 0 | 0 | 0 | 0 | |
PB2 | (n = 73) | (n = 626) | (n = 773) | (n = 1472) | (n = 28) | (n = 35) | |
T271A | 0.0 | 0.2 | 0 | 0.1 | 19.7 | 0 | |
526R | 0.0 | 3.4 | 3.5 | 3.3 | 3.8 | 0 | |
590S | 60.3 | 12.8 | 3.7 | 10.3 | 30.8 | 37.1 | |
591K | 0.0 | 1 | 1.1 | 1.0 | 0 | 2.9 | |
590S/591K | 0.0 | 0.3 | 0 | 0.1 | 0 | 0 | |
A588V | 6.9 | 5 | 29.1 | 17.8 | 46.2 | 11.4 | |
E627K | 4.1 | 1 | 1 | 1.1 | 3.6 | 8.6 | |
E627V | 0.0 | 12 | 4.4 | 7.4 | 21.4 | 0 | |
D701N | 0.0 | 0 | 0.1 | 0.1 | 3.7 | 2.9 | |
K702R | 26.0 | 12 | 2.1 | 7.5 | 15.4 | 42.9 | |
PB1 | (n = 71) | (n = 572) | (n = 564) | (n = 1207) | (n = 16) | (n = 24) | |
H99Y | 0 | 0 | 0 | 0 | 0 | 0 | |
327K | 0.0 | 0.5 | 0 | 0.2 | 0 | 0 | |
336I | 5.6 | 1.2 | 0.2 | 1.0 | 0 | 0 | |
I368V | 2.8 | 21.3 | 67.4 | 41.8 | 62.5 | 33.3 | |
PA | (n = 46) | (n = 605) | (n = 394) | (n = 1045) | (n = 28) | (n = 27) | |
85I | 0.0 | 0.2 | 0.0 | 0.1 | 0.0 | 0.0 | |
86S | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | |
100A | 0.0 | 0.7 | 14.7 | 5.9 | 0.0 | 18.5 | |
336M | 0.0 | 4.1 | 4.6 | 4.1 | 14.3 | 0.0 | |
356R | 2.0 | 5.5 | 82.7 | 34.4 | 57.1 | 25.9 | |
409N | 9.8 | 36.9 | 82.5 | 59.3 | 60.7 | 66.7 |
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Sun, X.; Belser, J.A.; Maines, T.R. Adaptation of H9N2 Influenza Viruses to Mammalian Hosts: A Review of Molecular Markers. Viruses 2020, 12, 541. https://doi.org/10.3390/v12050541
Sun X, Belser JA, Maines TR. Adaptation of H9N2 Influenza Viruses to Mammalian Hosts: A Review of Molecular Markers. Viruses. 2020; 12(5):541. https://doi.org/10.3390/v12050541
Chicago/Turabian StyleSun, Xiangjie, Jessica A. Belser, and Taronna R. Maines. 2020. "Adaptation of H9N2 Influenza Viruses to Mammalian Hosts: A Review of Molecular Markers" Viruses 12, no. 5: 541. https://doi.org/10.3390/v12050541