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Title: 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

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.

Authors:
 [1];  [2]; ; ;  [1];  [2];  [1];  [3];  [2]
  1. College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Heungduk-Ku, Cheongju 361-763 (Korea, Republic of)
  2. School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)
  3. College of Veterinary Medicine, Chungnam National University, 220 Gung-Dong, Yuseoung-Gu, DaeJeon 305-764 (Korea, Republic of)
Publication Date:
OSTI Identifier:
21357589
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 397; Journal Issue: 1; Other Information: DOI: 10.1016/j.virol.2009.10.041; PII: S0042-6822(09)00677-1; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; COPRECIPITATION; GENES; HOST; INFLUENZA VIRUSES; INTERACTIONS; MESSENGER-RNA; MODULATION; PROTEINS; YEASTS; EUMYCOTA; FUNGI; MICROORGANISMS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; PARASITES; PLANTS; PRECIPITATION; RNA; SEPARATION PROCESSES; VIRUSES

Citation Formats

Lee, Jun Han, Kim, Sung-Hak, Pascua, Philippe Noriel Q, Song, Min-Suk, Baek, Yun Hee, Jin, Xun, Choi, Joong-Kook, Kim, Chul-Joong, Kim, Hyunggee, and Choi, Young Ki, E-mail: choiki55@chungbuk.ac.k. 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. United States: N. p., 2010. Web. doi:10.1016/j.virol.2009.10.041.
Lee, Jun Han, Kim, Sung-Hak, Pascua, Philippe Noriel Q, Song, Min-Suk, Baek, Yun Hee, Jin, Xun, Choi, Joong-Kook, Kim, Chul-Joong, Kim, Hyunggee, & Choi, Young Ki, E-mail: choiki55@chungbuk.ac.k. 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. United States. doi:10.1016/j.virol.2009.10.041.
Lee, Jun Han, Kim, Sung-Hak, Pascua, Philippe Noriel Q, Song, Min-Suk, Baek, Yun Hee, Jin, Xun, Choi, Joong-Kook, Kim, Chul-Joong, Kim, Hyunggee, and Choi, Young Ki, E-mail: choiki55@chungbuk.ac.k. Fri . "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". United States. doi:10.1016/j.virol.2009.10.041.
@article{osti_21357589,
title = {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},
author = {Lee, Jun Han and Kim, Sung-Hak and Pascua, Philippe Noriel Q and Song, Min-Suk and Baek, Yun Hee and Jin, Xun and Choi, Joong-Kook and Kim, Chul-Joong and Kim, Hyunggee and Choi, Young Ki, E-mail: choiki55@chungbuk.ac.k},
abstractNote = {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.},
doi = {10.1016/j.virol.2009.10.041},
journal = {Virology},
issn = {0042-6822},
number = 1,
volume = 397,
place = {United States},
year = {2010},
month = {2}
}