Announcement

Collapse
No announcement yet.

Elucidating the interactions between influenza virus polymerase and host factor ANP32A

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

  • Elucidating the interactions between influenza virus polymerase and host factor ANP32A


    J Virol. 2019 Nov 6. pii: JVI.01353-19. doi: 10.1128/JVI.01353-19. [Epub ahead of print] Elucidating the interactions between influenza virus polymerase and host factor ANP32A.

    Mistry B1, Long JS1, Schreyer J1, Staller E1, Sanchez-David RY1, Barclay WS2.
    Author information

    1 Section of Molecular Virology, Imperial College London, St Mary's Campus, London, W2 1PG, UK. 2 Section of Molecular Virology, Imperial College London, St Mary's Campus, London, W2 1PG, UK w.barclay@imperial.ac.uk.

    Abstract

    The avian origin influenza A viral polymerase is restricted in human cells. This restriction has been associated with species differences in host factor ANP32A. Avian ANP32A supports the activity of an avian origin polymerase. However, the avian origin polymerase is incompatible with human ANP32A. Avian ANP32A proteins harbour an additional 33 amino acids compared to human ANP32A proteins, which are crucial for their ability to support the avian origin influenza polymerase. Here, we elucidate the interactions between ANP32A proteins and the influenza A viral polymerase using split luciferase complementation assays, co-immunoprecipitation and in situ split Venus interaction assays. We show greater interaction between chicken ANP32A and the viral polymerase compared to human ANP32A and visualise these interactions in situ in the cell nucleus. We demonstrate that the 33 amino acids of chicken ANP32A and the PB2 627 domain of viral polymerase complex both contribute to this enhanced interaction. Finally, we show how these interactions are affected by the presence of viral RNA and the processivity of the polymerase, giving insights into the way that ANP32A might act during virus infection.Importance Successful zoonotic transmission of influenza A virus into humans can lead to pandemics in an immunologically na?ve population. Host encoded ANP32A proteins are required to support influenza A polymerase activity, and species differences in ANP32A can restrict host range of influenza. Understanding how ANP32A proteins support the viral polymerase and how differences in ANP32A affect the ability of the polymerase to co-opt these proteins will enhance our understanding of viral replication and species restriction as well as suggesting targeted antiviral approaches to treat influenza infection.
    Copyright ? 2019 Mistry et al.


    PMID: 31694956 DOI: 10.1128/JVI.01353-19
    Free full text

Working...
X