anti-nucleocapsid protein immune responses counteract pathogenic effects of rift valley fever virus infection in miceanti-nucleocapsid蛋白免疫反应抵消致病性病毒感染裂谷热在小鼠的影响.pdf

Anti-Nucleocapsid Protein Immune Responses Counteract Pathogenic Effects of Rift Valley Fever Virus Infection in Mice Petrus Jansen van Vuren1,2, Caroline T. Tiemessen2,3, Janusz T. Paweska1,2* 1 Special Pathogens Unit, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham, South Africa, 2 Division Virology and Communicable Diseases Surveillance, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa, 3 Cell Biology/AIDS Virus Research Unit, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham, South Africa 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 IFNb 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-immuni