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Key molecular factors in hemagglutinin and PB2 contribute to efficient transmission of the 2009 H1N1 pandemic influenza virus.
J Virol. 2012 Sep; 86(18):9666-74.JV

Abstract

Animal influenza viruses pose a clear threat to public health. Transmissibility among humans is a prerequisite for a novel influenza virus to cause a human pandemic. A novel reassortant swine influenza virus acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. However, the molecular aspects of influenza virus transmission remain poorly understood. Here, we show that an amino acid in hemagglutinin (HA) is important for the 2009 H1N1 influenza pandemic virus (2009/H1N1) to bind to human virus receptors and confer respiratory droplet transmissibility in mammals. We found that the change from glutamine (Q) to arginine (R) at position 226 of HA, which causes a switch in receptor-binding preference from human α-2,6 to avian α-2,3 sialic acid, resulted in a virus incapable of respiratory droplet transmission in guinea pigs and reduced the virus's ability to replicate in the lungs of ferrets. The change from alanine (A) to threonine (T) at position 271 of PB2 also abolished the virus's respiratory droplet transmission in guinea pigs, and this mutation, together with the HA Q226R mutation, abolished the virus's respiratory droplet transmission in ferrets. Furthermore, we found that amino acid 271A of PB2 plays a key role in virus acquisition of the mutation at position 226 of HA that confers human receptor recognition. Our results highlight the importance of both the PB2 and HA genes on the adaptation and transmission of influenza viruses in humans and provide important insights for monitoring and evaluating the pandemic potential of field influenza viruses.

Authors+Show Affiliations

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22740390

Citation

Zhang, Ying, et al. "Key Molecular Factors in Hemagglutinin and PB2 Contribute to Efficient Transmission of the 2009 H1N1 Pandemic Influenza Virus." Journal of Virology, vol. 86, no. 18, 2012, pp. 9666-74.
Zhang Y, Zhang Q, Gao Y, et al. Key molecular factors in hemagglutinin and PB2 contribute to efficient transmission of the 2009 H1N1 pandemic influenza virus. J Virol. 2012;86(18):9666-74.
Zhang, Y., Zhang, Q., Gao, Y., He, X., Kong, H., Jiang, Y., Guan, Y., Xia, X., Shu, Y., Kawaoka, Y., Bu, Z., & Chen, H. (2012). Key molecular factors in hemagglutinin and PB2 contribute to efficient transmission of the 2009 H1N1 pandemic influenza virus. Journal of Virology, 86(18), 9666-74. https://doi.org/10.1128/JVI.00958-12
Zhang Y, et al. Key Molecular Factors in Hemagglutinin and PB2 Contribute to Efficient Transmission of the 2009 H1N1 Pandemic Influenza Virus. J Virol. 2012;86(18):9666-74. PubMed PMID: 22740390.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Key molecular factors in hemagglutinin and PB2 contribute to efficient transmission of the 2009 H1N1 pandemic influenza virus. AU - Zhang,Ying, AU - Zhang,Qianyi, AU - Gao,Yuwei, AU - He,Xijun, AU - Kong,Huihui, AU - Jiang,Yongping, AU - Guan,Yuntao, AU - Xia,Xianzhu, AU - Shu,Yuelong, AU - Kawaoka,Yoshihiro, AU - Bu,Zhigao, AU - Chen,Hualan, Y1 - 2012/06/27/ PY - 2012/6/29/entrez PY - 2012/6/29/pubmed PY - 2012/12/10/medline SP - 9666 EP - 74 JF - Journal of virology JO - J. Virol. VL - 86 IS - 18 N2 - Animal influenza viruses pose a clear threat to public health. Transmissibility among humans is a prerequisite for a novel influenza virus to cause a human pandemic. A novel reassortant swine influenza virus acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. However, the molecular aspects of influenza virus transmission remain poorly understood. Here, we show that an amino acid in hemagglutinin (HA) is important for the 2009 H1N1 influenza pandemic virus (2009/H1N1) to bind to human virus receptors and confer respiratory droplet transmissibility in mammals. We found that the change from glutamine (Q) to arginine (R) at position 226 of HA, which causes a switch in receptor-binding preference from human α-2,6 to avian α-2,3 sialic acid, resulted in a virus incapable of respiratory droplet transmission in guinea pigs and reduced the virus's ability to replicate in the lungs of ferrets. The change from alanine (A) to threonine (T) at position 271 of PB2 also abolished the virus's respiratory droplet transmission in guinea pigs, and this mutation, together with the HA Q226R mutation, abolished the virus's respiratory droplet transmission in ferrets. Furthermore, we found that amino acid 271A of PB2 plays a key role in virus acquisition of the mutation at position 226 of HA that confers human receptor recognition. Our results highlight the importance of both the PB2 and HA genes on the adaptation and transmission of influenza viruses in humans and provide important insights for monitoring and evaluating the pandemic potential of field influenza viruses. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/22740390/Key_molecular_factors_in_hemagglutinin_and_PB2_contribute_to_efficient_transmission_of_the_2009_H1N1_pandemic_influenza_virus_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=22740390 DB - PRIME DP - Unbound Medicine ER -