What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1?

Horby, Peter; Sudoyo, Herawati; Viprakasit, Vip; Fox, Annette; Thai, Pq Q.; Yu, Hongjie; Dávila, Sonia; Hibberd, Martin L.; Dunstan, Sarah J.; Monteerarat, Yuwarat; Farrar, Jeremy; Marzuki, Sangkot; Hien, N T

doi:10.1017/s0950268810000518

Cited by 52 publications

(48 citation statements)

References 73 publications

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“…This finding is in agreement with recent studies showing that exacerbated inflammatory responses often characterize mouse strains highly susceptible to influenza infection (6,7,58). Studies on human subjects have also suggested that susceptibility to influenza is shared by close relatives and is thus a heritable property (2,29). In our studies, although we have not determined the mechanisms that underlie the rapid weight loss induced by A/California/04/09 infection, we have found that mice of the most susceptible strain, A/J, become highly resistant to virus-induced weight loss and mortality if they are preexposed to a nonpathogenic seasonal strain of H1N1 virus, suggesting that immunological memory overrides the natural susceptibility of this mouse strain to the pandemic virus.…”

Section: Discussionsupporting

confidence: 92%

Infection with Seasonal Influenza Virus Elicits CD4 T Cells Specific for Genetically Conserved Epitopes That Can Be Rapidly Mobilized for Protective Immunity to Pandemic H1N1 Influenza Virus

Alam

Sant

2011

J Virol

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In recent years, influenza viruses with pandemic potential have been a major concern worldwide. One unresolved issue is how infection or vaccination with seasonal influenza virus strains influences the ability to mount a protective immune response to novel pandemic strains. In this study, we developed a mouse model of primary and secondary influenza infection by using a widely circulating seasonal H1N1 virus and the pandemic strain of H1N1 that emerged in Mexico in 2009, and we evaluated several key issues. First, using overlapping peptide libraries encompassing the entire translated sequences of 5 major influenza virus proteins, we assessed the specificity of CD4 T cell reactivity toward epitopes conserved among H1N1 viruses or unique to the seasonal or pandemic strain by enzyme-linked immunospot (ELISpot) assays. Our data show that CD4 T cells reactive to both virus-specific and genetically conserved epitopes are elicited, allowing separate tracking of these responses. Populations of cross-reactive CD4 T cells generated from seasonal influenza infection were found to expand earlier after secondary infection with the pandemic H1N1 virus than CD4 T cell populations specific for new epitopes. Coincident with this rapid CD4 T cell response was a potentiated neutralizing-antibody response to the pandemic strain and protection from the pathological effects of infection with the pandemic virus. This protection was not dependent on CD8 T cells. Together, our results indicate that exposure to seasonal vaccines and infection elicits CD4 T cells that promote the ability of the mammalian host to mount a protective immune response to pandemic strains of influenza virus.

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Section: Discussionsupporting

confidence: 92%

Infection with Seasonal Influenza Virus Elicits CD4 T Cells Specific for Genetically Conserved Epitopes That Can Be Rapidly Mobilized for Protective Immunity to Pandemic H1N1 Influenza Virus

Alam

Sant

2011

J Virol

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“…In fact, influenza virus infections with inbred mouse strains have demonstrated the importance of genetic factors to variation of susceptibility to influenza (39,40). Studies with family clusters of avian influenza virus H5N1 and case studies of H1N1pdm09 patients also imply that genetic factors affect susceptibility to pandemic influenza (41)(42)(43)(44)(45). Considering the distinct genetic and epigenetic background of each donor and difference between human and mouse studies, investigating the effect of genetic or epigenetic factors on influenza susceptibility in wellcontrolled human AECs, the cells most relevant to influenza, may provide unique advantage because the response in the same type of cells will not be affected by prior influenza history, vaccination, or other environmental exposure.…”

Section: Discussionmentioning

confidence: 99%

Differential Susceptibilities of Human Lung Primary Cells to H1N1 Influenza Viruses

Travanty

Zhou

et al. 2015

J Virol

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Human alveolar epithelial cells (AECs) and alveolar macrophages (AMs) are the first lines of lung defense. Here, we report that AECs are the direct targets for H1N1 viruses that have circulated since the 2009 pandemic (H1N1pdm09). AMs are less susceptible to H1N1pdm09 virus, but they produce significantly more inflammatory cytokines than AECs from the same donor. AECs form an intact epithelial barrier that is destroyed by H1N1pdm09 infection. However, there is significant variation in the cellular permissiveness to H1N1pdm09 infection among different donors. AECs from obese donors appear to be more susceptible to H1N1pdm09 infection, whereas gender, smoking history, and age do not appear to affect AEC susceptibility. There is also a difference in response to different strains of H1N1pdm09 viruses. Compared to A/California04/09 (CA04), A/New York/1682/09 (NY1682) is more infectious and causes more epithelial barrier injury, although it stimulates less cytokine production. We further determined that a single amino acid residue substitution in NY1682 hemagglutinin is responsible for the difference in infectivity. In conclusion, this is the first study of host susceptibility of human lung primary cells and the integrity of the alveolar epithelial barrier to influenza. Further elucidation of the mechanism of increased susceptibility of AECs from obese subjects may facilitate the development of novel protection strategies against influenza virus infection. IMPORTANCEDisease susceptibility of influenza is determined by host and viral factors. Human alveolar epithelial cells (AECs) form the key line of lung defenses against pathogens. Using primary AECs from different donors, we provided cellular level evidence that obesity might be a risk factor for increased susceptibility to influenza. We also compared the infections of two closely related 2009 pandemic H1N1 strains in AECs from the same donor and identified a key viral factor that affected host susceptibility, the dominance of which may be correlated with disease epidemiology. In addition, primary human AECs can serve as a convenient and powerful model to investigate the mechanism of influenza-induced lung injury and determine the effect of genetic and epigenetic factors on host susceptibility to pandemic influenza virus infection.

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“…This suggests the possibility of genetic susceptibility as a risk factor for infection [41][42][43].…”

Section: Discussionmentioning

confidence: 99%

Two clustered cases of confirmed influenza A(H5N1) virus infection, Cambodia, 2011

Chea¹,

Rith

et al. 2014

Eurosurveillance

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What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1?

Cited by 52 publications

References 73 publications

Infection with Seasonal Influenza Virus Elicits CD4 T Cells Specific for Genetically Conserved Epitopes That Can Be Rapidly Mobilized for Protective Immunity to Pandemic H1N1 Influenza Virus

Infection with Seasonal Influenza Virus Elicits CD4 T Cells Specific for Genetically Conserved Epitopes That Can Be Rapidly Mobilized for Protective Immunity to Pandemic H1N1 Influenza Virus

Differential Susceptibilities of Human Lung Primary Cells to H1N1 Influenza Viruses

Two clustered cases of confirmed influenza A(H5N1) virus infection, Cambodia, 2011

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