Drug Discov Ther. 2008;2(2):77-84.

Hsc70 regulates the nuclear export but not the import of influenza viral RNP: A possible target for the development of anti-influenza virus drugs.

Watanabe K, Takizawa N, Noda S, Tsukahara F, Maru Y, Kobayashi N,

In our previous report, we demonstrated that the matrix 1 (M1) protein of influenza virus directly binds to heat shock cognate protein 70 (Hsc70). The down-regulation of Hsc70 resulted in the reduction of influenza virus production, thus suggesting that Hsc70 plays a crucial role for viral replication. However, the detailed role of Hsc70 in viral replication remains to be elucidated. Hsc70 has been suggested to play a significant role in both the nuclear import and export processes. In this report, using leptomycin B (LMB), a CRM1-mediated nuclear export inhibitor, we demonstrated that Hsc70 forms a complex with vRNP through M1 in infected cells and in the virion, thus playing a significant role in the export of vRNP from the nucleus but not in the import of vRNP into the nucleus. The regulation of Hsc70 may therefore lead to the development of new anti-influenza virus drugs without raising mutant viruses.

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