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Truncation of C-terminal 20 amino acids in PA-X contributes to adaptation of swine influenza virus in pigs

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  • Truncation of C-terminal 20 amino acids in PA-X contributes to adaptation of swine influenza virus in pigs

    Sci Rep. 2016 Feb 25;6:21845. doi: 10.1038/srep21845.
    Truncation of C-terminal 20 amino acids in PA-X contributes to adaptation of swine influenza virus in pigs.

    Xu G1, Zhang X1, Sun Y1, Liu Q2, Sun H1, Xiong X1, Jiang M1, He Q1, Wang Y1, Pu J1, Guo X1, Yang H1, Liu J1.
    Author information

    Abstract

    The PA-X protein is a fusion protein incorporating the N-terminal 191 amino acids of the PA protein with a short C-terminal sequence encoded by an overlapping ORF (X-ORF) in segment 3 that is accessed by + 1 ribosomal frameshifting, and this X-ORF exists in either full length or a truncated form (either 61-or 41-condons). Genetic evolution analysis indicates that all swine influenza viruses (SIVs) possessed full-length PA-X prior to 1985, but since then SIVs with truncated PA-X have gradually increased and become dominant, implying that truncation of this protein may contribute to the adaptation of influenza virus in pigs. To verify this hypothesis, we constructed PA-X extended viruses in the background of a "triple-reassortment" H1N2 SIV with truncated PA-X, and evaluated their biological characteristics in vitro and in vivo. Compared with full-length PA-X, SIV with truncated PA-X had increased viral replication in porcine cells and swine respiratory tissues, along with enhanced pathogenicity, replication and transmissibility in pigs. Furthermore, we found that truncation of PA-X improved the inhibition of IFN-I mRNA expression. Hereby, our results imply that truncation of PA-X may contribute to the adaptation of SIV in pigs.


    PMID: 26912401 [PubMed - in process]
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