Viperin: A Cellular Inhibitor of DNA and RNA Viruses

Tue, 12/24/2013 - 10:55

Viperin (Virus Inhibitory Protein, Endoplasmic Reticulum-associated, Interferon-inducible) inhibits the replication of a broad spectrum of viruses by several diverse mechanisms. The protein was first identified in 2001, when it was found to be the product of an IFN gamma-inducible gene (1).

Viperin is encoded by the RSAD2 gene, and is composed of three distinct domains. The central domain and C-terminal domain are highly conserved, whilst the N-terminal domain shows variability in length and sequence between species, and is necessary for the correct localization and function of the protein. The central domain contains an S-Adenosyl-L-Methionine (SAM) domain, which has a CX3CX2C motif that is involved in iron-sulphur cluster binding and is critical for the conformational stability of the protein (2).

Many experiments have been carried out to try and establish the mechanism by which Viperin performs its anti-viral function. The vast majority of these have involved in vitro viral infection of cell lines and the use of Viperin over-expression to inhibit viral replication, or Viperin RNAi to assess the effect of knocking down the protein (3). Since this work has been performed with a wide range of viruses, all with very different infection routes and replication mechanisms, it has been extremely difficult to elucidate exactly how Viperin exerts its effects. Wang et al. demonstrated that overexpression of Viperin in HeLa cells inhibited the budding and release of Influenza A virus by binding to and inhibiting farnesyl diphosphate synthase (FPPS), an enzyme involved in the synthesis of isoprenoid-derived lipids, and that this could be reversed by over-expressing FPPS (4). Seo et al. showed that human cytomegalovirus (HCMV) can induce Viperin expression independently of the interferon response, and uses this to drive lipogenesis in infected cells thereby facilitating development of the membrane envelope (5).  Helbig et al. illustrated that infection of various cell lines with Dengue virus type-2 (DENV-2) induced Viperin expression, and that this subsequently inhibited DENV-2 RNA production (6).

  1. PMID: 11752458
  2. PMID: 22363738
  3. PMID: 22177558
  4. PMID: 18005724
  5. PMID: 23935494
  6. PMID: 23638199

Novus Biologicals offers various Viperin reagents for your research needs, including:

Written by Emma Easthope


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