Our laboratory and others have previously shown that the interferon (IFN) stimulated gene, viperin has anti-viral actions against dengue virus (DENV) in vitro (1). Here we have extended this to study DENV induction of viperin in vivo and DENV replication in viperin deficient (vip-/-) mice.
Intracranial DENV infection in WT mice results in infection in the brain and eye and an increase in viperin mRNA quantitated by RT-PCR in both of these tissues. Subcutaneous DENV-infection in AG129, IFN-receptor deficient mice also results in increased viperin, demonstrating IFN-independent mechanisms for induction of viperin in vivo. In the absence of viperin, replication of DENV was enhanced in primary murine embryonic fibroblasts (MEF) derived from vip-/- mice, consistent with previous data (1). In contrast, DENV infection and RNA levels following subcutaneous or intracranial challenge were not significantly different between wild type (WT) and vip-/- mice. Interestingly, brain IL-6 mRNA levels were significantly higher following intracranial DENV infection in vip-/- than WT mice. Further analysis is underway to assess the effect of the lack of viperin on DENV-infection and inflammatory responses in the eye.
Thus, viperin has anti-viral actions against DENV in vitro and can be induced by DENV infection in vivo including through IFN-independent mechanisms and in tissues such as the eye. DENV infection is not altered in vip-/- mice suggesting compensation in vivo for the lack of viperin, potentially by other anti-viral responses such as IL-6 production, that maintains immune control of DENV-infection.
(1) Helbig et al., (2013) PNTD 7:e2178