Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 41, Issue 3, Pages 554-560Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2008.07.001
Keywords
Influenza virus; Nucleoprotein; Intrabodies; Protein interaction; Viral replication
Categories
Funding
- Major State Basic Research Development Program of China [2005CB522901, 2005CB522905]
- National Natural Science Foundation of China [30730001, 30570070]
- Innovative Research Team in University [IRT0745]
- Department of Science Technology of Hubei Province [2005ABC003]
- Science and Technology Programs of Wuhan [200760323102]
- HEC (Pakistan)
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Influenza A virus is responsible for influenza epidemics in avian and human populations and poses a great threat to human health. Many researches have been focused on the prevention and treatment of influenza A virus infection. The nucleoprotein (NP) of the virus is an important protein due to its ability to interact with a variety of viral and cellular factors and its role in the viral RNA synthesis. In this study, we have used the influenza A virus nucleoprotein as target for anti-viral therapy through a new approach. By screening a human single-chain intracellular antibody (intrabody) cDNA library using nucleoprotein as bait in a yeast antigen-antibody two-hybrid system, we have identified several intrabodies that specifically interact with the viral nucleoprotein. Interaction between nucleoprotein and anti-nucleoprotein intrabodies was further confirmed by mammalian two-hybrid analysis. Results showed that anti-nucleoprotein intrabodies changed their cellular distribution in association with the viral nucleoprotein. Further studies indicated that anti-nucleoprotein intrabodies abolished the accumulation of not only the complementary RNA and virion RNA but also messenger RNA of influenza virus. In addition, anti-nucleoprotein intrabodies significantly inhibited influenza A virus transcription and replication through blocking the interaction of nucleoprotein with the viral polymerase proteins, polymerase basic protein 1 and polymerase basic protein 2. Thus, this study not only provides a powerful tool for the study of viral protein's functions, but also opens a new potential avenue for the prevention and treatment of influenza virus infections. (C) 2008 Elsevier Ltd. All rights reserved.
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