title: Anti-nucleocapsid protein immune responses counteract pathogenic effects of Rift Valley fever virus infection in mice.
abstract: The known virulence factor of Rift Valley fever virus (RVFV), the NSs protein, counteracts the antiviral effects of the type I interferon response. In this study we evaluated the expression of several genes in the liver and spleen involved in innate and adaptive immunity of mice immunized with a RVFV recombinant nucleocapsid protein (recNP) combined with Alhydrogel adjuvant and control animals after challenge with wild type RVFV. Mice immunized with recNP elicited an earlier IFNβ response after challenge compared to non-immunized controls. In the acute phase of liver infection in non-immunized mice there was a massive upregulation of type I and II interferon, accompanied by high viral titers, and the up- and downregulation of several genes involved in the activation of B- and T-cells, indicating that both humoral and cellular immunity is modulated during RVFV infection. Various genes involved in pro-inflammatory responses and with pro-apoptotic effects were strongly upregulated and anti-apoptotic genes were downregulated in liver of non-immunized mice. Expression of many genes involved in B- and T-cell immunity were downregulated in spleen of non-immunized mice but normal in immunized mice. A strong bias towards apoptosis and inflammation in non-immunized mice at an acute stage of liver infection associated with suppression of several genes involved in activation of humoral and cellular immunity in spleen, suggests that RVFV evades the host immune response in more ways than only by inhibition of type I interferon, and that immunopathology of the liver plays a crucial role in RVF disease progression.
authors.affiliation: Special Pathogens Unit, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham, South Africa.
authors.forename: Petrus
authors.initials: P
authors.lastname: Jansen van Vuren
authors.forename: Caroline T
authors.initials: CT
authors.lastname: Tiemessen
authors.forename: Janusz T
authors.initials: JT
authors.lastname: Paweska
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D007111:Immunity, Cellular; D007114:Immunization; D008099:Liver / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019251:Nucleocapsid / Q000276:immunology*; D019590:Nucleocapsid Proteins / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D012295:Rift Valley Fever / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D012296:Rift Valley fever virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage*; D014771:Virion / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D004279:DNA, Viral; D019590:Nucleocapsid Proteins; D014765:Viral Vaccines