The type I interferon system protects mice from Semliki Forest virus by preventing widespread virus dissemination in extraneural tissues, but does not mediate the restricted replication of avirulent virus in central nervous system neurons

Fragkoudis, R., Breakwell, L., McKimmie, C., Boyd, A., Barry, G., Kohl, A. , Merits, A. and Fazakerley, J. K. (2007) The type I interferon system protects mice from Semliki Forest virus by preventing widespread virus dissemination in extraneural tissues, but does not mediate the restricted replication of avirulent virus in central nervous system neurons. Journal of General Virology, 88(12), pp. 3373-3384. (doi:10.1099/vir.0.83191-0)

Fragkoudis, R., Breakwell, L., McKimmie, C., Boyd, A., Barry, G., Kohl, A. , Merits, A. and Fazakerley, J. K. (2007) The type I interferon system protects mice from Semliki Forest virus by preventing widespread virus dissemination in extraneural tissues, but does not mediate the restricted replication of avirulent virus in central nervous system neurons. Journal of General Virology, 88(12), pp. 3373-3384. (doi:10.1099/vir.0.83191-0)

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Publisher's URL: http://dx.doi.org/10.1099/vir.0.83191-0

Abstract

Semliki Forest virus (SFV) infection of the mouse provides a powerful model to study the pathogenesis of virus encephalitis. SFV and other alphavirus-based vector systems are increasingly used in biotechnology and medicine. This study analysed the strong susceptibility of this virus to type I interferon (IFN) responses. Following intraperitoneal infection of adult mice, SFV strain A7(74) was efficiently (100 %) neuroinvasive. In contrast, SFV4 was poorly (21 %) neuroinvasive. Upon entry into the brain, both viruses activated type I IFN responses. As determined by quantitative RT-PCR, activation of the IFN-α gene was proportional to virus RNA load. An intact type I IFN system was required for protection against both strains of SFV. IFN strongly curtailed virus spread in many cell types and in many tissues. In mice with an intact type I IFN system, infected cells were rarely observed and tissue tropism was difficult to determine. In the absence of a functional type I IFN system, the tropism and the potential for rapid and widespread infection of this virus was revealed. Virus infection was readily observed in the myocardium, endocardium, exocrine pancreas, adipose tissue, smooth muscle cells and in the brain in meningeal cells, ependymal cells and oligodendrocytes. In the brains of mice with and without type I IFN responses, virus infection of neurons remained rare and focal, indicating that the previously described restricted replication of SFV A7(74) in neurons is not mediated by type I IFN responses.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McKimmie, Dr Clive and Kohl, Professor Alain and Barry, Dr Gerald
Authors: Fragkoudis, R., Breakwell, L., McKimmie, C., Boyd, A., Barry, G., Kohl, A., Merits, A., and Fazakerley, J. K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of General Virology
Publisher:Society for General Microbiology
ISSN:0022-1317
ISSN (Online):1465-2099

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