tetano
Editor, Senior Moderator
J Virol. 2019 Nov 27. pii: JVI.01410-19. doi: 10.1128/JVI.01410-19. [Epub ahead of print] [h=1]Viral determinants in H5N1 influenza A virus enable productive infection of HeLa cells.[/h]
Rodriguez-Frandsen A[SUP]1[/SUP], Martin-Sancho L[SUP]1[/SUP], Gounder AP[SUP]1[/SUP], Chang MW[SUP]2[/SUP], Liu WC[SUP]3,[/SUP][SUP]4[/SUP], De Jesus PD[SUP]1[/SUP], von Recum-Knepper J[SUP]1[/SUP], Dutra MS[SUP]1[/SUP], Huffmaster NJ[SUP]1[/SUP], Chavarria M[SUP]1[/SUP], Mena I[SUP]3,[/SUP][SUP]4[/SUP], Riva L[SUP]1[/SUP], Nguyen CB[SUP]1[/SUP], Dobariya S[SUP]1[/SUP], Herbert KM[SUP]1[/SUP], Benner C[SUP]2[/SUP], Albrecht RA[SUP]3,[/SUP][SUP]4[/SUP], Garc?a-Sastre A[SUP]3,[/SUP][SUP]4,[/SUP][SUP]5,[/SUP][SUP]6[/SUP], Chanda SK[SUP]7[/SUP].
[h=3]Author information[/h] 1 Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. 2 Department of Medicine, University of California, San Diego, CA, USA. 3 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4 Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 5 Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 6 The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 7 Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. schanda@sbpdiscovery.org.
[h=3]Abstract[/h] Influenza A virus (IAV) is a human respiratory pathogen that causes yearly global epidemics, and sporadic pandemics due to human adaptation of pathogenic strains. Efficient replication of IAV in different species is, in part, dictated by its ability to exploit the genetic environment of the host cell. To investigate IAV tropism in human cells, we evaluated the replication of IAV strains in a diverse subset of epithelial cell lines. HeLa cells were refractory to growth of human H1N1 and H3N2, and low pathogenic avian influenza (LPAIs) viruses. Interestingly, a human isolate of the highly pathogenic avian influenza (HPAI) virus H5N1 successfully propagated in HeLa cells to levels comparable to a human lung cell line. Heterokaryon cells generated by fusion of HeLa and permissive cells supported H1N1 growth, suggesting the absence of a host factor(s) required for replication of H1N1, but not H5N1, in HeLa cells. The absence of this factor(s) was mapped to reduced nuclear import, replication, and translation, and deficient viral budding. Using reassortant H1N1:H5N1 viruses, we found that the combined introduction of nucleoprotein (NP) and hemagglutinin (HA) from H5N1 was necessary and sufficient to enable H1N1 growth. Overall, this study suggests the absence of one or more cellular factors in HeLa cells that results in abortive replication of H1N1, H3N2, and LPAI viruses, but can be circumvented upon introduction of H5N1 NP and HA. Further understanding of the molecular basis of this restriction will provide important insights into virus-host interactions that underlie IAV pathogenesis and tropism.IMPORTANCE Many zoonotic avian influenza A viruses have successfully crossed the species barrier and caused mild to life-threatening disease in humans. While human-to-human transmission is limited, there is a risk for these zoonotic viruses to acquire adaptive mutations to efficiently propagate and cause devastating human pandemics. Therefore, it is important to identify viral determinants that provide these viruses with a replicative advantage in human cells. Here, we tested growth of influenza A virus in a subset of human cell lines and found that abortive replication of H1N1 viruses in HeLa cells can be circumvented upon introduction of H5N1 HA and NP proteins. Overall, this work leverages the genetic diversity of multiple human cell lines to highlight viral determinants that could contribute to H5N1 pathogenesis and tropism.
Copyright ? 2019 American Society for Microbiology.
PMID: 31776276 DOI: 10.1128/JVI.01410-19
Rodriguez-Frandsen A[SUP]1[/SUP], Martin-Sancho L[SUP]1[/SUP], Gounder AP[SUP]1[/SUP], Chang MW[SUP]2[/SUP], Liu WC[SUP]3,[/SUP][SUP]4[/SUP], De Jesus PD[SUP]1[/SUP], von Recum-Knepper J[SUP]1[/SUP], Dutra MS[SUP]1[/SUP], Huffmaster NJ[SUP]1[/SUP], Chavarria M[SUP]1[/SUP], Mena I[SUP]3,[/SUP][SUP]4[/SUP], Riva L[SUP]1[/SUP], Nguyen CB[SUP]1[/SUP], Dobariya S[SUP]1[/SUP], Herbert KM[SUP]1[/SUP], Benner C[SUP]2[/SUP], Albrecht RA[SUP]3,[/SUP][SUP]4[/SUP], Garc?a-Sastre A[SUP]3,[/SUP][SUP]4,[/SUP][SUP]5,[/SUP][SUP]6[/SUP], Chanda SK[SUP]7[/SUP].
[h=3]Author information[/h] 1 Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. 2 Department of Medicine, University of California, San Diego, CA, USA. 3 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4 Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 5 Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 6 The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 7 Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. schanda@sbpdiscovery.org.
[h=3]Abstract[/h] Influenza A virus (IAV) is a human respiratory pathogen that causes yearly global epidemics, and sporadic pandemics due to human adaptation of pathogenic strains. Efficient replication of IAV in different species is, in part, dictated by its ability to exploit the genetic environment of the host cell. To investigate IAV tropism in human cells, we evaluated the replication of IAV strains in a diverse subset of epithelial cell lines. HeLa cells were refractory to growth of human H1N1 and H3N2, and low pathogenic avian influenza (LPAIs) viruses. Interestingly, a human isolate of the highly pathogenic avian influenza (HPAI) virus H5N1 successfully propagated in HeLa cells to levels comparable to a human lung cell line. Heterokaryon cells generated by fusion of HeLa and permissive cells supported H1N1 growth, suggesting the absence of a host factor(s) required for replication of H1N1, but not H5N1, in HeLa cells. The absence of this factor(s) was mapped to reduced nuclear import, replication, and translation, and deficient viral budding. Using reassortant H1N1:H5N1 viruses, we found that the combined introduction of nucleoprotein (NP) and hemagglutinin (HA) from H5N1 was necessary and sufficient to enable H1N1 growth. Overall, this study suggests the absence of one or more cellular factors in HeLa cells that results in abortive replication of H1N1, H3N2, and LPAI viruses, but can be circumvented upon introduction of H5N1 NP and HA. Further understanding of the molecular basis of this restriction will provide important insights into virus-host interactions that underlie IAV pathogenesis and tropism.IMPORTANCE Many zoonotic avian influenza A viruses have successfully crossed the species barrier and caused mild to life-threatening disease in humans. While human-to-human transmission is limited, there is a risk for these zoonotic viruses to acquire adaptive mutations to efficiently propagate and cause devastating human pandemics. Therefore, it is important to identify viral determinants that provide these viruses with a replicative advantage in human cells. Here, we tested growth of influenza A virus in a subset of human cell lines and found that abortive replication of H1N1 viruses in HeLa cells can be circumvented upon introduction of H5N1 HA and NP proteins. Overall, this work leverages the genetic diversity of multiple human cell lines to highlight viral determinants that could contribute to H5N1 pathogenesis and tropism.
Copyright ? 2019 American Society for Microbiology.
PMID: 31776276 DOI: 10.1128/JVI.01410-19