Human Parainfluenza Virus Type 1 C Proteins Are Nonessential Proteins That Inhibit the Host Interferon and Apoptotic Responses and Are Required for Efficient Replication in Nonhuman Primates

• DOI: 10.1128/jvi.00853-08
• Publication Date: 2008-07-10T00:45:18Z
• Authors: Emmalene J. Bartlett; Ann-Marie Cruz; Janice Esker; Adam Castaño; Henrick Schomacker; Sonja R. Surman; Margaret Hennessey; Jim Boonyaratanak...; Raymond J. Pickles; Peter L. Collins; Brian R. Murphy; Alexander C. Schmidt
• Keywords: Cytopathic effect

Recombinant human parainfluenza virus type 1 (rHPIV1) was modified to create rHPIV1-P(C-), a in which expression of the C proteins (C', C, Y1, and Y2) silenced without affecting amino acid sequence P protein. Infectious rHPIV1-P(C-) readily recovered from cDNA, indicating that four were not essential for replication. Early during infection vitro, replicated as efficiently wild-type (wt) HPIV1, but its titer subsequently decreased coincident with onset an extensive cytopathic effect observed wt rHPIV1. infection, rHPIV1 induced caspase 3 activation nuclear fragmentation LLC-MK2 cells, identifying HPIV1 inhibitors apoptosis. In contrast rHPIV1, rHPIV1-C(F170S), mutant encoding F170S substitution interferon (IFN) did inhibit IFN signaling vitro. However, only Thus, anti-IFN antiapoptosis activities separable: both are disabled whereas activity is rHPIV1-C(F170S). African green monkeys (AGMs), considerably more attenuated than suggesting disabling antiapoptotic had additive effects on attenuation vivo. Although protected against challenge highly restricted replication AGMs primary airway epithelial cell cultures suggests it might be overattenuated use vaccine. nonessential have required virulence primates.