Viperin
| Radical S-adenosyl methionine domain-containing protein 2 | |
|---|---|
| Identifiers | |
| Symbol | RSAD2 |
| Entrez | 91543 |
| HUGO | 30908 |
| OMIM | 607810 |
| RefSeq | NM_080657 |
| UniProt | Q8WXG1 |
| Other data | |
| Locus | Chr. 2 p25.2 |
Viperin (Virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible),[1] also known as RSAD2 (radical SAM domain-containing 2), is a multifunctional protein in viral processes, which could be induced in a variety of cell types by different cellular factors, such as type I II and III interferon, DNA and RNA viral proteins, poly (I: C) and polysaccharide. Recently, it is reported that viperin could be induced in either IFN-dependent or IFN-independent pathway.
Function
Viperin is a cellular protein which could inhibit many DNA and RNA viruses such as CHIKV, HCMV, HCV, DENV, WNV, SINV, influenza, HIV LAI strain, and so on.[2] Initially identified as an IFN-γ induced antiviral protein in human cytomegalovirus (HCMV) infected macrophages, viperin is reported that it could be induced by HCMV glycoprotein B in fibroblasts but inhibits HCMV viral infection and down-regulates viral structural proteins, which is essential for viral assembling and maturation. The mechanism of how the virus protein induces viperin against itself is still not clear. However, the viral induced redistribution of Viperin is also found in HCMV infected cells, which may reflect the mechanism of virus evading antiviral activities of Viperin.[3] Viperin could also be induced, and then interact with HCMV viral proteins and relocate to mitochondria in HCMV viral infected cells, and finally enhance viral infectivity by the disrupted cellular metabolism.[4]
In the inhibition of influenza virus budding and release, viperin could disrupt the lipid rafts on cell plasma membrane by decreasing the enzyme activities of farnesyl diphosphate synthase (FPPS), which is an essential enzyme in isoprenoid biosynthesis pathway.[5] Besides, viperin can also inhibit the viral replication of HCV via the interaction with host protein hVAP-33 and NS5A and disruption of the formation of the replication complex.[6]
Structure
Human Viperin consists of 361 amino acids, and it is a single polypeptide chain with a predicted 42kDa molecular mass. The first 42 residues of human viperin is the N-terminal amphipathic alpha-helix, which is relatively less conserved in different species and has a minor effect on the antiviral ability of viperin against HCV, WNV and DENV. The N-terminal domain of viperin is also required for the viperin localization in ER and the lipid droplets.[7] The residues 77-209 constitute the radical S-adenosylmethionine (SAM) domain, in which there are four conserved motifs. Motif 1 contains three conserved cysteine residues, CxxCxxC, which is the Fe-S binding motif and also essential for the antiviral activities against HCV and HCMV infections.[4] The 218-361 residues constitute the C-terminal domain of viperin, which is highly conserved in different species of viperin and essential for viperin dimerization. The last residue 361 of the C-terminal, a tryptophan, is essential for the antiviral activities against HCV since a C-terminal flag tagged of viperin lost its antiviral activities.[8] Viperin forms homodimers in ER, and the over expression of viperin could lead the formation of a crystalloid ER.
Cellular localization
Viperin is normally localized in endoplasmic reticulum (ER) via its N-terminal domain, and also localized to lipid droplet, which is derived from ER.[7] However, it is also found in mitochondria in the HCMV infected fibroblasts by a viral mediated mechanism.[4]
References
- ↑ Jun-Young Seo; Rakina Yaneva; Peter Cresswell (December 2011). "Viperin: A Multifunctional, Interferon-Inducible Protein that Regulates Virus Replication". Cell Host and Microbe. 10 (6): 534–9. doi:10.1016/j.chom.2011.11.004. PMC 3246677. PMID 22177558.
- ↑ Mattijssen S, Pruijn GJ (May 2012). "Viperin, a key player in the antiviral response". Microbes Infect. 14 (5): 419–26. doi:10.1016/j.micinf.2011.11.015. PMID 22182524.
- ↑ Chin KC, Cresswell P (December 2001). "Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus". Proc Natl Acad Sci U S A. 98 (26): 15125–30. Bibcode:2001PNAS...9815125C. doi:10.1073/pnas.011593298. PMC 64994. PMID 11752458.
- ↑ 4.0 4.1 4.2 Seo JY, Yaneva R, Hinson ER, Cresswell P; Yaneva; Hinson; Cresswell (April 2011). "Human cytomegalovirus directly induces the antiviral protein viperin to enhance infectivity". Science. 332 (6033): 1093–7. Bibcode:2011Sci...332.1093S. doi:10.1126/science.1202007. PMID 21527675.
- ↑ Wang X, Hinson ER, Cresswell P (August 2007). "The interferon-inducible protein viperin inhibits influenza virus release by perturbing lipid rafts". Cell Host Microbe. 2 (2): :96–105. doi:10.1016/j.chom.2007.06.009. PMID 18005724.
- ↑ Helbig KJ, Eyre NS, Yip E, Narayana S, Li K, Fiches G, McCartney EM, Jangra RK, Lemon SM, Beard MR (November 2011). "The antiviral protein viperin inhibits hepatitis C virus replication via interaction with nonstructural protein 5A". Hepatology. 54 (5): 1506–17. doi:10.1002/hep.24542. PMC 3207276. PMID 22045669.
- ↑ 7.0 7.1 Hinson ER, Cresswell P (December 2009). "The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic alpha-helix". Proc Natl Acad Sci U S A. 106 (48): 20452–7. Bibcode:2009PNAS..10620452H. doi:10.1073/pnas.0911679106. PMC 2778571. PMID 19920176.
- ↑ Jiang D, Guo H, Xu C, Chang J, Gu B, Wang L, Block TM, Guo JT (February 2008). "Identification of three interferon-inducible cellular enzymes that inhibit the replication of hepatitis C virus". J Virol. 82 (4): 1665–78. doi:10.1128/JVI.02113-07. PMC 2258705. PMID 18077728.