Attenuating mutations in the P/C gene of human parainfluenza virus type 1 (HPIV1) vaccine candidates abrogate the inhibition of both induction and signaling of type I interferon (IFN) by wild-type HPIV1
| Autor: | William Van Cleve, Mario H. Skiadopoulos, Joseph Bekisz, Sonja R. Surman, Peter L. Collins, Kathryn C. Zoon, Brian R. Murphy, Emerito Amaro-Carambot, Emmalene J. Bartlett |
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| Rok vydání: | 2006 |
| Předmět: |
Mutant
Context (language use) Biology Vaccines Attenuated Human parainfluenza virus Cell Line Viral Proteins Interferon Virology Chlorocebus aethiops Attenuating mutation medicine Animals Humans Point Mutation Parainfluenza Vaccines Vero Cells A549 cell Wild type Interferon antagonist Phosphoproteins In vitro Parainfluenza Virus 1 Human Interferon Type I Vero cell Antagonism Signal Transduction medicine.drug Vaccine candidate |
| Zdroj: | Virology. 352(1):61-73 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2006.04.011 |
| Popis: | Recombinant human parainfluenza virus type 1 (HPIV1) and mutants containing point and deletion (Δ) mutations in the P/C gene (r-C Δ10–15 HN T553A , r-C R84G , r-C F170S and r-C Δ170 ), which have previously been evaluated as HPIV1 vaccine candidates, were evaluated for their effect on the type I interferon (IFN) response in vitro. HPIV1 wt infection inhibited the IFN response by inhibiting IFN regulatory factor-3 (IRF-3) activation and IFN production in A549 cells and IFN signaling in Vero cells. In contrast, r-C R84G , r-C F170S and r-C Δ170 were defective for inhibition of IRF-3 activation and IFN production and r-C F170S and r-C Δ170 did not inhibit IFN signaling. Thus, HPIV1 antagonizes the IFN response at both the level of induction and signaling, and antagonism at both levels was disrupted by mutations in the P/C gene. Because C F170S affects C and not P, the anti-IFN function can be attributed to the C proteins. These data, in the context of previous in vivo studies, suggest that the loss of antagonism of the IFN response at both the level of induction and signaling, observed with the P/C mutants, r-C F170S and r-C Δ170 , was necessary for significant attenuation in African green monkeys (AGMs). |
| Databáze: | OpenAIRE |
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