Is flavivirus resistance interferon type I-independent?
Interferon type I comprises a group of major virus-inducible host antiviral factors that control infection with a great number of human and animal viruses. They are ubiquitously expressed cytokines that interfere with virus replication within different cell types by activating a number of host genes and several parallel antiviral pathways. Two major intracellular actors of IFN-I-induced antiviral states are ribonucleic acid-dependent protein kinase and 2'-5'-oligoadenylate synthetases/RNase L, both being induced by IFN-I and activated by viral double stranded ribonucleic acid. In addition, Mx proteins and ribonucleic acid-specific adenosine deaminase have also been implicated in IFN-I-induced antiviral responses to some RNA viruses. Viruses, in turn, have evolved different strategies to escape a control imposed by IFN-I and by IFN-I-induced antiviral factors. The fatal outcome of virus infection as well as the efficiency of IFN-I-based antiviral therapies in its prevention, are determined by complex interactions between viral virulence factors and cellular antiviral IFN-I inducible factors. In the light of these facts and current knowledge on IFN-I involvement in flavivirus infection, I discuss a possible role of IFN-I signalling in resistance to flavivirus infection in a model of congenic mouse strains that express different levels of susceptibility/resistance to common flaviviruses. Specifically, this review emphasizes importance of fully operative 2'-5'-oligoadenylate synthetases/RNase L pathway for the IFN-I-induced stimulation of flavivirus resistance conferred by Flv.
Urosevic
Nadezda
N
Microbiology, School of Biomedical and Chemical Science, University of Western Australia, Nedlands, Australia. nadia@cyllene.uwa.edu.au
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000818:Animals; D004198:Disease Susceptibility; D005416:Flavivirus / Q000276:immunology*; D018177:Flavivirus Infections / Q000276:immunology*; D006801:Humans; D007304:Insect Viruses / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
D007370:Interferon Type I; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase