The NS1 protein of influenza A virus interacts with heat shock protein Hsp90 in human alveolar basal epithelial cells: implication for virus-induced apoptosis.

Abstract

BACKGROUND:

Our previous study showed that the NS1 protein of highly pathogenic avian influenza A virus H5N1 induced caspase-dependent apoptosis in human alveolar basal epithelial cells (A549), supporting its function as a proapoptotic factor during viral infection, but the mechanism is still unknown.

RESULTS:

To characterize the mechanism of NS1-induced apoptosis, we used a two-hybrid system to isolate the potential NS1-interacting partners in A549 cells. We found that heat shock protein 90 (Hsp90) was able to interact with the NS1 proteins derived from both H5N1 and H3N2 viruses, which was verified by co-immunoprecitation assays. Significantly, the NS1 expression in the A549 cells dramatically weakened the interaction between Apaf-1 and Hsp90 but enhanced its interaction with cytochrome c (Cyt c), suggesting that the competitive binding of NS1 to Hsp90 might promote the Apaf-1 to associate with Cyt c and thus facilitate the activation of caspase 9 and caspase 3.

CONCLUSIONS:

The present results demonstrate that NS1 protein of Influenza A Virus interacts with heat hock protein Hsp90 and meidates the apoptosis induced by influenza A virus through the caspase cascade.

• Authors: Chuanfu Zhang, Yutao Yang, Xiaowei Zhou, Zhixin Yang, Xuelin Liu, Zhiliang Cao, Hongbin Song, Yuxian He, Peitang Huang
• Journal: Virology journal (Virol J) Vol. 8 Pg. 181 (Apr 19 2011) ISSN: 1743-422X [Electronic] England
• PMID: 21501532 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HSP90 Heat-Shock Proteins
• INS1 protein, influenza virus
• Viral Nonstructural Proteins

Topics

• Apoptosis
• Cell Line
• Epithelial Cells (virology)
• HSP90 Heat-Shock Proteins (metabolism)
• Humans
• Immunoprecipitation
• Influenza A Virus, H3N2 Subtype (pathogenicity)
• Influenza A Virus, H5N1 Subtype (pathogenicity)
• Influenza, Human (pathology)
• Protein Binding
• Protein Interaction Mapping
• Two-Hybrid System Techniques
• Viral Nonstructural Proteins (metabolism)