Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2019

The role of viperin in dengue virus infection (#46)

Jillian M Carr 1 , Wisam H AlShujairi 1 , Kylie Van der Hoek 2 , Michael R Beard 2
  1. Flinders University, BEDFORD, SA, Australia
  2. School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia

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