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Genetic compatibility and virulence of reassortants derived from contemporary avian H5N1 and human H3N2 influenza A viruses.
PLoS Pathog 2008; 4(5):e1000072PP

Abstract

The segmented structure of the influenza virus genome plays a pivotal role in its adaptation to new hosts and the emergence of pandemics. Despite concerns about the pandemic threat posed by highly pathogenic avian influenza H5N1 viruses, little is known about the biological properties of H5N1 viruses that may emerge following reassortment with contemporary human influenza viruses. In this study, we used reverse genetics to generate the 63 possible virus reassortants derived from H5N1 and H3N2 viruses, containing the H5N1 surface protein genes, and analyzed their viability, replication efficiency, and mouse virulence. Specific constellations of avian-human viral genes proved deleterious for viral replication in cell culture, possibly due to disruption of molecular interaction networks. In particular, striking phenotypes were noted with heterologous polymerase subunits, as well as NP and M, or NS. However, nearly one-half of the reassortants replicated with high efficiency in vitro, revealing a high degree of compatibility between avian and human virus genes. Thirteen reassortants displayed virulent phenotypes in mice and may pose the greatest threat for mammalian hosts. Interestingly, one of the most pathogenic reassortants contained avian PB1, resembling the 1957 and 1968 pandemic viruses. Our results reveal the broad spectrum of phenotypes associated with H5N1/H3N2 reassortment and a possible role for the avian PB1 in the emergence of pandemic influenza. These observations have important implications for risk assessment of H5N1 reassortant viruses detected in surveillance programs.

Authors+Show Affiliations

Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

18497857

Citation

Chen, Li-Mei, et al. "Genetic Compatibility and Virulence of Reassortants Derived From Contemporary Avian H5N1 and Human H3N2 Influenza a Viruses." PLoS Pathogens, vol. 4, no. 5, 2008, pp. e1000072.
Chen LM, Davis CT, Zhou H, et al. Genetic compatibility and virulence of reassortants derived from contemporary avian H5N1 and human H3N2 influenza A viruses. PLoS Pathog. 2008;4(5):e1000072.
Chen, L. M., Davis, C. T., Zhou, H., Cox, N. J., & Donis, R. O. (2008). Genetic compatibility and virulence of reassortants derived from contemporary avian H5N1 and human H3N2 influenza A viruses. PLoS Pathogens, 4(5), pp. e1000072. doi:10.1371/journal.ppat.1000072.
Chen LM, et al. Genetic Compatibility and Virulence of Reassortants Derived From Contemporary Avian H5N1 and Human H3N2 Influenza a Viruses. PLoS Pathog. 2008 May 23;4(5):e1000072. PubMed PMID: 18497857.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic compatibility and virulence of reassortants derived from contemporary avian H5N1 and human H3N2 influenza A viruses. AU - Chen,Li-Mei, AU - Davis,C Todd, AU - Zhou,Hong, AU - Cox,Nancy J, AU - Donis,Ruben O, Y1 - 2008/05/23/ PY - 2008/02/21/received PY - 2008/04/15/accepted PY - 2008/5/24/pubmed PY - 2008/8/6/medline PY - 2008/5/24/entrez SP - e1000072 EP - e1000072 JF - PLoS pathogens JO - PLoS Pathog. VL - 4 IS - 5 N2 - The segmented structure of the influenza virus genome plays a pivotal role in its adaptation to new hosts and the emergence of pandemics. Despite concerns about the pandemic threat posed by highly pathogenic avian influenza H5N1 viruses, little is known about the biological properties of H5N1 viruses that may emerge following reassortment with contemporary human influenza viruses. In this study, we used reverse genetics to generate the 63 possible virus reassortants derived from H5N1 and H3N2 viruses, containing the H5N1 surface protein genes, and analyzed their viability, replication efficiency, and mouse virulence. Specific constellations of avian-human viral genes proved deleterious for viral replication in cell culture, possibly due to disruption of molecular interaction networks. In particular, striking phenotypes were noted with heterologous polymerase subunits, as well as NP and M, or NS. However, nearly one-half of the reassortants replicated with high efficiency in vitro, revealing a high degree of compatibility between avian and human virus genes. Thirteen reassortants displayed virulent phenotypes in mice and may pose the greatest threat for mammalian hosts. Interestingly, one of the most pathogenic reassortants contained avian PB1, resembling the 1957 and 1968 pandemic viruses. Our results reveal the broad spectrum of phenotypes associated with H5N1/H3N2 reassortment and a possible role for the avian PB1 in the emergence of pandemic influenza. These observations have important implications for risk assessment of H5N1 reassortant viruses detected in surveillance programs. SN - 1553-7374 UR - https://www.unboundmedicine.com/medline/citation/18497857/Genetic_compatibility_and_virulence_of_reassortants_derived_from_contemporary_avian_H5N1_and_human_H3N2_influenza_A_viruses_ L2 - http://dx.plos.org/10.1371/journal.ppat.1000072 DB - PRIME DP - Unbound Medicine ER -