Host specificity of the anti-interferon and anti-apoptosis activities of parainfluenza virus P/C gene products.
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-kappaB, resulting in an increased level of IFN-beta 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-beta 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.
Chambers
Raychel
R
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Takimoto
Toru
T
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D006801:Humans; D007372:Interferons / Q000037:antagonists & inhibitors*; D051379:Mice; D010222:Parainfluenza Virus 1, Human / Q000235:genetics / Q000276:immunology*; D010750:Phosphoproteins / Q000235:genetics* / Q000276:immunology*; D011995:Recombination, Genetic; D029082:Sendai virus / Q000235:genetics* / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology*
C055859:P protein, Sendai virus; D010750:Phosphoproteins; D014764:Viral Proteins; C051221:nonstructural C protein, Sendai virus; C068855:P protein, parainfluenza virus 1; C068856:C protein, human parainfluenza virus type 1; D007372:Interferons