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.
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Raychel
R
Chambers
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Toru
T
Takimoto
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