Interaction of Hsp40 with influenza virus M2 protein: implications for PKR signaling pathway

Zhenhong Guan1, Di Liu, Shuofu Mi

  • 1College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.

Protein & Cell
|January 5, 2011
PubMed

Insights

Influenza virus M2 proteins from both A and B strains interact with human Hsp40 and p58(IPK). This interaction enhances PKR signaling, potentially impacting virus replication and infected cell survival.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Biology

Background:

  • Influenza virus M2 protein is crucial for virus uncoating and replication.
  • Hsp40 (DnaJ/Hsp40 family) is known to regulate the PKR signaling pathway via p58(IPK).
  • PKR is a key component of the host antiviral defense.

Purpose of the Study:

  • To identify cellular proteins interacting with influenza virus M2.
  • To investigate the role of M2 protein in the Hsp40/p58(IPK)/PKR signaling pathway.
  • To understand how M2 influences virus replication and infected cell fate.

Main Methods:

  • Yeast two-hybrid system to screen for M2-interacting proteins.
  • In vitro and in vivo interaction assays (co-immunoprecipitation).
  • Mapping of interaction domains.
  • Analysis of PKR signaling pathway activation.

Main Results:

  • Influenza A and B M2 proteins (A/M2 and BM2) interact with human Hsp40.
  • Interaction between M2 and Hsp40 is mapped to the CTD1 domain of Hsp40.
  • Both A/M2 and BM2 bind to p58(IPK).
  • M2 proteins, in complex with Hsp40 and p58(IPK), enhance PKR autophosphorylation, leading to cell death.

Conclusions:

  • Influenza virus M2 protein interacts with Hsp40 and p58(IPK).
  • M2 modulates the p58(IPK)-mediated PKR pathway during infection.
  • This interaction affects the infected-cell life cycle and influenza virus replication.

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