[Show abstract][Hide abstract] ABSTRACT: Classical swine fever virus (CSFV) is capable of counteracting innate cellular antiviral responses by inhibiting type I interferon (IFN)-alpha/beta induction. A function associated with CSFV N(pro), with respect to the inhibition of IFN-beta production, has been clearly elucidated. In this study, we explored the role of CSFV E(rns) in IFN-beta induction by exogenous double-stranded (ds) RNA. Synthetic dsRNA (poly (IC)) was used as an exogenous stimulus to trigger IFN-beta induction. CSFV E(rns) inhibited IFN-beta promoter-driven luciferase activity induced by poly (IC) in different cell lines, and the inhibitory effect was dose-dependent. Moreover, E(rns) reduced IFN-beta mRNA synthesis and blocked IFN-alpha/beta production induced by poly (IC), suggesting that this inhibition occurs at the transcriptional level. Furthermore, E(rns) counteracted poly (IC)-mediated IFN-beta induction independent of its ribonuclease activity. In conclusion, CSFV E(rns) antagonizes extracellular dsRNA-mediated IFN-beta expression. These findings contribute to our understanding of the pathogenesis of CSFV.
Canadian Journal of Microbiology 06/2009; 55(6):698-704. DOI:10.1139/w09-013 · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: DNA vaccination is an effective means of eliciting both humoral and cellular immune responses. The hemagglutinin (HA) surface protein of influenza A virus is a major target of protective antibody responses induced by virus infection or by vaccination and is widely considered to be the antigen of choice for an influenza vaccine. Cytotoxic T lymphocyte (CTL) responses directed against the conserved nucleoprotein (NP) are thought to play an important role in clearing virus and promoting survival and recovery from influenza. In this study, we developed a novel DNA vaccine approach using a chimeric plasmid consisting of the HA of H5N1 influenza virus in which an MHC class I-restricted NP-specific CTL epitope (NP147–155) was inserted. Immunogenicity and antiviral efficacy of this vaccine was assessed in mouse models. A similar level of HA expression was achieved in 293T cells transfected with pHA/NP147–155 compared to that with pHA. Besides eliciting the specific anti-HA antibody responses, vaccination using pHA/NP147–155 in mice induced NP epitope-specific CD8+ T cell responses, which are generally not inducible by vaccination with pHA alone. After H5N1 influenza virus challenge, BALB/c mice vaccinated with pHA/NP147–155 exhibited reduced inflammation severity and lung viral titers compared to those vaccinated with pHA. Our work may contribute to improvement of HA-based influenza DNA vaccines.
Antiviral Research 03/2009; DOI:10.1016/j.antiviral.2008.12.009 · 3.94 Impact Factor