%0 Journal Article
%T ISG15 facilitates cellular antiviral response to dengue and west nile virus infection in vitro
%A Jianfeng Dai
%A Wen Pan
%A Penghua Wang
%J Virology Journal
%D 2011
%I BioMed Central
%R 10.1186/1743-422x-8-468
%X Quantitative PCR showed that mouse Isg15 was dramatically induced in DENV or WNV- infected RAW264.7 cells compared with non-infected cells. Isg15 and two other Jak-Stat related genes, Socs1 and Socs3, were silenced using siRNA mediated RNA interference. The intracellular DENV and WNV loads, as determined by quantitative PCR, were significantly higher in Isg15 silenced cells than control cells. The expression levels of interferon beta 1 (Ifnb1) were increased significantly in Isg15, Socs1 or Socs3 siRNA treated cells. Further investigation indicated that protein modification by ISG15, so called ISGylation, was significantly enhanced in DENV-infected cells compared to that in non-infected cells.These findings suggest that ISG15 plays an anti-DENV/WNV function via protein ISGylation.Dengue virus (DENV) and West Nile virus (WNV) are two major flaviviruses that can infect human via mosquito bites [1]. Both viruses are (+) sense single strand RNA viruses and replicate in the cytoplasm of their host cells. DENV infection causes Dengue fever (DF) or Dengue hemorrhagic fever (DHF), and the latter may lead to death of the patient [2]. WNV is a re-emerging zoonotic pathogen of medical importance. In humans, WNV infection may cause life-threatening meningoencephalitis or long-term neurologic sequelae [3]. Vaccines against both DENV and WNV are currently not available, thus much efforts are needed to elucidate the mammalian host anti-viral mechanisms against these two flaviviruses in vitro and in vivo [1-3].ISG15 is one of the first identified Interferon-Stimulated- Genes (ISGs). The expression of ISG15 can be induced by type I interferons (IFNs), viral infections and LPS, suggesting that ISG15 is a broad spectrum of stress response gene [4,5]. The protein product of ISG15 shows a significant sequence homology to ubiqutin, and this protein can conjugate to numerous cellular proteins via isopeptide bonds. This kind of protein modification is called ISGylation, which also utilizes
%K ISG15
%K Dengue Virus
%K West Nile Virus
%K ISGylation
%U http://www.virologyj.com/content/8/1/468