conserved charged amino acids within sendai virus c protein play multiple roles in the evasion of innate immune responses守恒的带电氨基酸在仙台病毒c蛋白扮演多个角色逃税的先天免疫反应.pdf

Conserved Charged Amino Acids within Sendai Virus C Protein Play Multiple Roles in the Evasion of Innate Immune Responses Takashi Irie*, Natsuko Nagata, Tomoki Igarashi, Isao Okamoto, Takemasa Sakaguchi Department of Virology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan Abstract One of the accessory proteins of Sendai virus (SeV), C, translated from an alternate reading frame of P/V mRNA has been shown to function at multiple stages of infection in cell cultures as well as in mice. C protein has been reported to counteract signal transduction by interferon (IFN), inhibit apoptosis induced by the infection, enhance the efficiency of budding of viral particles, and regulate the polarity of viral genome-length RNA synthesis to maximize production of infectious particles. In this study, we have generated a series of SeV recombinants containing substitutions of highly conserved, charged residues within the C protein, and characterized them together with previously-reported C9/C( 2), 4C( 2), and F170S recombinant viruses in infected cell cultures in terms of viral replication, cytopathogenicity, and antagonizing effects on host innate immunity. Unexpectedly, the amino acid substitutions had no or minimal effect on viral growth and viral RNA synthesis. However, all the substitutions of charged amino acids resulted in the loss of a counteracting effect against the establishment of an IFN-a-mediated anti-viral state. Infection by the virus (Cm29) containing mutations at K77 and D80 induced significant IFN-b production, severe cytopathic effects, and detectable amounts of viral dsRNA production. In addition to the Cm29 virus, the virus containing mutations at E114 and E115 did not inhibit the poly(I:C)- triggered translocati