1887

Abstract

Human parainfluenza virus type 1 (HPIV-1) and Sendai virus (SeV) are highly homologous in structure and sequence, whilst maintaining distinct host ranges. These viruses express accessory proteins from their P/C gene that are known to have activities against innate immunity. The accessory proteins expressed from the P/C gene of these viruses are different. In addition to the nested set of C proteins, SeV expresses V protein from edited P mRNA, which is not expressed by HPIV-1. This study evaluated the host specificity and role of the P/C gene products in anti-interferon (IFN) and anti-apoptosis activity by characterizing a recombinant SeV, rSeVhP, in which the SeV P/C gene was replaced with that of HPIV-1. Unlike SeV, rSeVhP infection strongly activated IFN regulatory transcription factor (IRF)-3 and nuclear factor-B, resulting in an increased level of IFN- induction compared with SeV in murine cells. In contrast, activation of IRF-3 was not observed in rSeVhP-infected human A549 cells. rSeVhPSV, which expressed SeV V protein from an inserted gene in rSeVhP, induced less IFN- than rSeVhP, suggesting that V contributes to the suppression of IFN production in murine cells. Furthermore, rSeVhP induced apoptotic cell death in murine but not in A549 cells. These data indicate the functional difference in P/C gene products from SeV and HPIV-1 in antagonizing IFN induction and apoptosis, which is likely to be one of the major factors for pathogenicity in specific hosts.

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2009-08-01
2021-03-08
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