The Type I Interferon response is a central player in the innate resistance to viral infection. The power of this system to restrict viral spread is illustrated by the number and diversity of mechanisms that many different viruses have evolved to counteract and subvert this system (McInerney and Karlsson Hedestam, 2009)
We showed that the main determinant of IFN evasion in SFV is non-structural protein 2 (nsP2). Infection of cells with viral mutant (SFV-RDR) which lacks a nuclear localisation sequence in the nsP2 protein, provokes the production of significantly increased levels of type I IFN and other pro-inflammatory cytokines. Our work suggests that this effect is independent of the general shut off of RNA and protein synthesis in SFV-infected cells and we are working to understand the mechanism by which this is achieved.
The interaction between alphaviruses and the type I IFN system is a focus of ongoing work in the laboratory.
Publications on this topic
Kuri, T., Smed-Sörensen, A., Thomas, S., Karlsson Hedestam, G.B., Henriques Normark, B., McInerney, G.M. and Plant, L. (2013) Influenza virus enhances IL-12p70 secretion by human dendritic cells infected with Streptococcus pneumoniae. Cellular Micro, 15:1385-400.
Arnold, C.N., Pirie, E., Dosenovic, P., McInerney, G.M., Siggs, O.M., Xia, Y., Karlsson Hedestam, G.B., and Beutler, B. (2012) A forward genetic screen reveals novel roles for Nfkbid, Zeb1, and Ruvbl2 in humoral immune responses. PNAS, 109:12286-12293.
McInerney, G.M. and Karlsson Hedestam, G.B. (2009). Direct cleavage, Proteasomal Degradation and Sequestration: Three mechanisms of viral subversion of type I interferon responses. Review. J Innate Immun 1:599-606.
Breakwell, L., Dosenovic, P., Karlsson Hedestam, G.B., D'Amato, M., Liljeström, P., Fazakerley, J. and McInerney, G.M. (2007). Semliki Forest virus non-structural protein 2 is involved in the suppression of the type I Interferon response. J Virol 81:8677-8684.