ISG15 over-expression inhibits replication of the Japanese encephalitis virus in human medulloblastoma cells

Hsiao, Nai Wan; Chen, Jiun Wei; Yang, Tsuey Ching; Orloff, Gregg M.; Wu, Yi; Lai, Chih Ho; Lan, Yu Ching; Lin, Cheng Wen

doi:10.1016/j.antiviral.2009.12.007

Cited by 55 publications

(37 citation statements)

References 38 publications

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“…ISG15 was also found to modify the influenza A non-structural protein NS1A, and inhibit its immunosuppressive function [15]. Little work has been done on the physiological relevancies of ISG15 to flavivirus infections [14,20]. Surprisingly though, a recent study even showed that ISG15 is favorable of hepatitis C virus infection [21].…”

Section: Resultsmentioning

confidence: 99%

ISG15 facilitates cellular antiviral response to dengue and west nile virus infection in vitro

Dai

Pan

Wang

2011

Virol J

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BackgroundDengue virus (DENV) and West Nile virus (WNV), close siblings of the Flaviviridae family, are the causative agents of Dengue hemorraghic shock or West Nile meningoencephalitis respectively. Vaccines against these two flaviviruses are currently unavailable. Interferon- Stimulated Gene 15 (ISG15), encoding an ubiquitin-like protein, is significantly induced by type I interferons or viral infections. Its roles in viral infections, however, vary with viruses, being either anti- or pro-viral. The exact roles of ISG15 in DENV and WNV infections remain unknown. In the current study, we evaluated the relevancies of ISG15 to DENV and WNV infection of a mouse macrophage cell line RAW264.7.FindingsQuantitative 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.ConclusionsThese findings suggest that ISG15 plays an anti-DENV/WNV function via protein ISGylation.

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Section: Resultsmentioning

confidence: 99%

ISG15 facilitates cellular antiviral response to dengue and west nile virus infection in vitro

Dai

Pan

Wang

2011

Virol J

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“…Given the association of OAS with the flavivirus-resistance phenomenon in mice (Brinton & Perelygin, 2003), this ISG most likely also plays an important role in recovery from JEV infection. ISG-15 is an additional ISG recently documented to be involved in the control of JEV infection (Hsiao et al, 2010). Considering its antiviral action, the therapeutic potential of recombinant IFN in human cases of JE has been investigated.…”

Section: Type 1 Interferon Induction and Signallingmentioning

confidence: 99%

“…ISGs serve as mediators of IFN action directed towards initiation of antiviral and immunoregulatory functions (Borden et al, 2007). Antiviral proteins associated with flaviviral infections include double-stranded RNA-activated protein kinase (PKR), the 2',5'-oligoadenylate synthetases (2'-5'-OAS), ISG15, ISG20, viperin and IFN-induced transmembrane proteins (Brass et al, 2009;Hsiao et al, ;Jiang et al, 2010;Kajaste-Rudnitski et al, 2006;Samuel et al, 2006). Of these, 2'-5'-OAS proteins are the most widely studied and acts through activation of RNase L, a potent endoribonuclease that cleaves viral RNA (Silverman, 2007).…”

Section: Type 1 Interferon Induction and Signallingmentioning

confidence: 99%

Immunobiology of Japanese Encephalitis Virus

Larena¹,

Lobigs²

2011

Flavivirus Encephalitis

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“…IFN-induced ISG15 conjugation plays an important antiviral role against several viruses, including influenza A and B viruses, Sindbis virus, herpes simplex virus type 1, murine gammaherpes virus, Japanese encephalitis virus, and vaccinia virus (8)(9)(10)(11)(12)(13). A major mechanism by which ISG15 conjugation inhibits one of these viruses, influenza A virus, has been identified (10,14).…”

mentioning

confidence: 99%

Structural basis for the sequence-specific recognition of human ISG15 by the NS1 protein of influenza B virus

Guan

Chung

Leonard

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Interferon-induced ISG15 conjugation plays an important antiviral role against several viruses, including influenza viruses. The NS1 protein of influenza B virus (NS1B) specifically binds only human and nonhuman primate ISG15s and inhibits their conjugation. To elucidate the structural basis for the sequence-specific recognition of human ISG15, we determined the crystal structure of the complex formed between human ISG15 and the N-terminal region of NS1B (NS1B-NTR). The NS1B-NTR homodimer interacts with two ISG15 molecules in the crystal and also in solution. The two ISG15-binding sites on the NS1B-NTR dimer are composed of residues from both chains, namely residues in the RNA-binding domain (RBD) from one chain, and residues in the linker between the RBD and the effector domain from the other chain. The primary contact region of NS1B-NTR on ISG15 is composed of residues at the junction of the N-terminal ubiquitin-like (Ubl) domain and the short linker region between the two Ubl domains, explaining why the sequence of the short linker in human and nonhuman primate ISG15s is essential for the species-specific binding of these ISG15s. In addition, the crystal structure identifies NS1B-NTR binding sites in the N-terminal Ubl domain of ISG15, and shows that there are essentially no contacts with the C-terminal Ubl domain of ISG15. Consequently, NS1B-NTR binding to ISG15 would not occlude access of the C-terminal Ubl domain of ISG15 to its conjugating enzymes. Nonetheless, transfection assays show that NS1B-NTR binding of ISG15 is responsible for the inhibition of interferoninduced ISG15 conjugation in cells.

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ISG15 over-expression inhibits replication of the Japanese encephalitis virus in human medulloblastoma cells

Cited by 55 publications

References 38 publications

ISG15 facilitates cellular antiviral response to dengue and west nile virus infection in vitro

ISG15 facilitates cellular antiviral response to dengue and west nile virus infection in vitro

Immunobiology of Japanese Encephalitis Virus

Structural basis for the sequence-specific recognition of human ISG15 by the NS1 protein of influenza B virus

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