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Genetic compatibility and virulence of reassortants derived from contemporary avian H5N1 and human H3N2 influenza A viruses.

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.

SUBMITTER: Chen LM

PROVIDER: S-EPMC2374906 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Genetic compatibility and virulence of reassortants derived from contemporary avian H5N1 and human H3N2 influenza A viruses.

Chen Li-Mei LM Davis C Todd CT Zhou Hong H Cox Nancy J NJ Donis Ruben O RO

PLoS pathogens 20080523 5

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 vi ...[more]

PMID: 18497857

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Project description:The cocirculation of H5N1 and H9N2 avian influenza viruses in birds in Egypt provides reassortment opportunities between these two viruses. However, little is known about the emergence potential of reassortants derived from Egyptian H5N1 and H9N2 viruses and about the biological properties of such reassortants. To evaluate the potential public health risk of reassortants of these viruses, we used reverse genetics to generate the 63 possible reassortants derived from contemporary Egyptian H5N1 and H9N2 viruses, containing the H5N1 surface gene segments and combinations of the H5N1 and H9N2 internal gene segments, and analyzed their genetic compatibility, replication ability, and virulence in mice. Genes in the reassortants showed remarkably high compatibility. The replication of most reassortants was higher than the parental H5N1 virus in human cells. Six reassortants were thought to emerge in birds under neutral or positive selective pressure, and four of them had higher pathogenicity in vivo than the parental H5N1 and H9N2 viruses. Our results indicated that H5N1-H9N2 reassortants could be transmitted efficiently to mammals with significant public health risk if they emerge in Egypt, although the viruses might not emerge frequently in birds.IMPORTANCE Close interaction between avian influenza (AI) viruses and humans in Egypt appears to have resulted in many of the worldwide cases of human infections by both H5N1 and H9N2 AI viruses. Egypt is regarded as a hot spot of AI virus evolution. Although no natural reassortant of H5N1 and H9N2 AI viruses has been reported so far, their cocirculation in Egypt may allow emergence of reassortants that may present a significant public health risk. Using reverse genetics, we report here the first comprehensive data showing that H5N1-N9N2 reassortants have fairly high genetic compatibility and possibly higher pathogenicity in mammals, including humans, than the parental viruses. Our results provide insight into the emergence potential of avian H5N1-H9N2 reassortants that may pose a high public health risk.

Dataset Information

Genetic compatibility and virulence of reassortants derived from contemporary avian H5N1 and human H3N2 influenza A viruses.

Publications

Genetic compatibility and virulence of reassortants derived from contemporary avian H5N1 and human H3N2 influenza A viruses.

Similar Datasets

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