Giuseppe
Emeritus
J Virol. 2008 Dec 3. [Epub ahead of print]
The influenza A virus polymerase is an integral component of the NS1A protein:CPSF30 complex in infected cells.
Kuo RL, Krug RM. - Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, Texas 78712.
The NS1A protein of influenza A virus binds the cellular CPSF30 protein, thereby inhibiting the 3' end processing of all cellular pre-mRNAs, including IFN-beta pre-mRNA.
X-ray crystallography identified the CPSF30-binding pocket on the influenza A/Udorn/72 (Ud) NS1A protein and the critical role of two hydrophobic NS1A amino acids outside the pocket, F103 and M106, in stabilizing the CPSF30:NS1A complex.
Although the NS1A protein of the 1997 H5N1 influenza A/Hong Kong/483/97 (HK97) virus contains L (not F) at 103 and I (not M) at 106, it binds CPSF30 in vivo to a significant extent because cognate (HK97) internal proteins stabilize the CPSF30:NS1A complex in infected cells.
Here we show that the cognate HK97 polymerase complex, containing the viral polymerase (PB1, PB2, PA proteins) and the nucleocapsid protein (NP), is responsible for this stabilization.
The non-cognate Ud polymerase complex cannot carry out this stabilization, whereas it can stabilize CPSF30 binding to a mutated (F103L, M106I) cognate Ud NS1A protein.
These results suggested that the viral polymerase complex is an integral component of the CPSF30:NS1A protein complex in infected cells even when the cognate NS1A protein contains F103 and M106, and we show that this is indeed the case.
Finally, we show that cognate PA and NP proteins, but not cognate PB1 and PB2 proteins, are required for stabilizing the CPSF30:NS1A complex, indicating that the NS1A protein interacts primarily with its cognate PA and NP proteins in a complex that includes the cellular CPSF30 protein.
PMID: 19052083 [PubMed - as supplied by publisher]
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The influenza A virus polymerase is an integral component of the NS1A protein:CPSF30 complex in infected cells.
Kuo RL, Krug RM. - Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, Texas 78712.
The NS1A protein of influenza A virus binds the cellular CPSF30 protein, thereby inhibiting the 3' end processing of all cellular pre-mRNAs, including IFN-beta pre-mRNA.
X-ray crystallography identified the CPSF30-binding pocket on the influenza A/Udorn/72 (Ud) NS1A protein and the critical role of two hydrophobic NS1A amino acids outside the pocket, F103 and M106, in stabilizing the CPSF30:NS1A complex.
Although the NS1A protein of the 1997 H5N1 influenza A/Hong Kong/483/97 (HK97) virus contains L (not F) at 103 and I (not M) at 106, it binds CPSF30 in vivo to a significant extent because cognate (HK97) internal proteins stabilize the CPSF30:NS1A complex in infected cells.
Here we show that the cognate HK97 polymerase complex, containing the viral polymerase (PB1, PB2, PA proteins) and the nucleocapsid protein (NP), is responsible for this stabilization.
The non-cognate Ud polymerase complex cannot carry out this stabilization, whereas it can stabilize CPSF30 binding to a mutated (F103L, M106I) cognate Ud NS1A protein.
These results suggested that the viral polymerase complex is an integral component of the CPSF30:NS1A protein complex in infected cells even when the cognate NS1A protein contains F103 and M106, and we show that this is indeed the case.
Finally, we show that cognate PA and NP proteins, but not cognate PB1 and PB2 proteins, are required for stabilizing the CPSF30:NS1A complex, indicating that the NS1A protein interacts primarily with its cognate PA and NP proteins in a complex that includes the cellular CPSF30 protein.
PMID: 19052083 [PubMed - as supplied by publisher]
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