Direct interaction of cellular hnRNP-F and NS1 of influenza A virus accelerates viral replication by modulation of viral transcriptional activity and host gene expression

Jun Han Lee, Sung Hak Kim, Philippe Noriel Q. Pascua, Min Suk Song, Yun Hee Baek, Xun Jin, Joong Kook Choi, Chul Joong Kim, Hyunggee Kim, Young Ki Choi

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

To investigate novel NS1-interacting proteins, we conducted a yeast two-hybrid analysis, followed by co-immunoprecipitation assays. We identified heterogeneous nuclear ribonucleoprotein F (hnRNP-F) as a cellular protein interacting with NS1 during influenza A virus infection. Co-precipitation assays suggest that interaction between hnRNP-F and NS1 is a common and direct event among human or avian influenza viruses. NS1 and hnRNP-F co-localize in the nucleus of host cells, and the RNA-binding domain of NS1 directly interacts with the GY-rich region of hnRNP-F determined by GST pull-down assays with truncated proteins. Importantly, hnRNP-F expression levels in host cells indicate regulatory role on virus replication. hnRNP-F depletion by small interfering RNA (siRNA) shows 10- to 100-fold increases in virus titers corresponding to enhanced viral RNA polymerase activity. Our results delineate novel mechanism of action by which NS1 accelerates influenza virus replication by modulating normal cellular mRNA processes through direct interaction with cellular hnRNP-F protein.

Original languageEnglish
Pages (from-to)89-99
Number of pages11
JournalVirology
Volume397
Issue number1
DOIs
Publication statusPublished - 2010 Feb 5

Keywords

  • Immunoprecipitation
  • Influenza A virus
  • NS1
  • Virus replication
  • hnRNP-F

ASJC Scopus subject areas

  • Virology

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