1887

Abstract

Hepatitis E virus (HEV) ORF1 protein (pORF1) contains methyltransferase (MetT), papain-like cysteine protease (PCP), RNA helicase (Hel) and RNA-dependent RNA polymerase (RdRp) domains. ORF1 sequence analysis showed two consensus LXGG cleavage sites at 664 and 1205. LXGG sequence is recognized by viral and cellular deubiquitinating enzymes. The protein encompassing the predicted MetT-PCP domains of HEV ORF1 was tested for deubiquitinating activity using fluorogenic substrates – ubiquitin-7-amino-4-methylcoumarin (AMC), IFN-stimulated gene 15 (ISG15)-AMC, Nedd8-AMC and SUMO-AMC. MetT-PCP cleaved all four substrates but processing of ISG15-AMC was more robust. There was no processing of the Hel and RdRp domains having the conserved (1205) LXGG site by the protein. MetT-PCP carried out deISGylation of the ISG15-conjugated cellular proteins, suggesting a possible role in combating cellular antiviral pathways.

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2011-09-01
2024-12-14
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References

  1. Agrawal S., Gupta D., Panda S. K. 2001; The 3′ end of hepatitis E virus (HEV) genome binds specifically to the viral RNA-dependent RNA polymerase (RdRp). Virology 282:87–101 [View Article][PubMed]
    [Google Scholar]
  2. Ansari I. H., Nanda S. K., Durgapal H., Agrawal S., Mohanty S. K., Gupta D., Jameel S., Panda S. K. 2000; Cloning, sequencing, and expression of the hepatitis E virus (HEV) nonstructural open reading frame 1 (ORF1). J Med Virol 60:275–283 [View Article][PubMed]
    [Google Scholar]
  3. Balakirev M. Y., Jaquinod M., Haas A. L., Chroboczek J. 2002; Deubiquitinating function of adenovirus proteinase. J Virol 76:6323–6331 [View Article][PubMed]
    [Google Scholar]
  4. Barretto N., Jukneliene D., Ratia K., Chen Z., Mesecar A. D., Baker S. C. 2005; The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity. J Virol 79:15189–15198 [View Article][PubMed]
    [Google Scholar]
  5. d'Azzo A., Bongiovanni A., Nastasi T. 2005; E3 ubiquitin ligases as regulators of membrane protein trafficking and degradation. Traffic 6:429–441 [View Article][PubMed]
    [Google Scholar]
  6. Frias-Staheli N., Giannakopoulos N. V., Kikkert M., Taylor S. L., Bridgen A., Paragas J., Richt J. A., Rowland R. R., Schmaljohn C. S. et al. 2007; Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses. Cell Host Microbe 2:404–416 [View Article][PubMed]
    [Google Scholar]
  7. Gale M. Jr, Tan S.-L., Katze M. G. 2000; Translational control of viral gene expression in eukaryotes. Microbiol Mol Biol Rev 64:239–280 [View Article][PubMed]
    [Google Scholar]
  8. Graff J., Torian U. H., Nguyen H., Emerson S. U. 2006; A bicistronic subgenomic mRNA encodes both the ORF2 and ORF3 proteins of hepatitis E virus. J Virol 80:5919–5926 [View Article][PubMed]
    [Google Scholar]
  9. Haglund K., Dikic I. 2005; Ubiquitylation and cell signaling. EMBO J 24:3353–3359 [View Article][PubMed]
    [Google Scholar]
  10. Herold J., Siddell S. G., Gorbalenya A. E. 1999; A human RNA viral cysteine proteinase that depends upon a unique Zn2+-binding finger connecting the two domains of a papain-like fold. J Biol Chem 274:14918–14925 [View Article][PubMed]
    [Google Scholar]
  11. Karpe Y. A., Lole K. S. 2010a; RNA 5′-triphosphatase activity of the hepatitis E virus helicase domain. J Virol 84:9637–9641 [View Article][PubMed]
    [Google Scholar]
  12. Karpe Y. A., Lole K. S. 2010b ). NTPase and 5′ to 3′ RNA duplex-unwinding activities of the hepatitis E virus helicase domain. J Virol 84:3595–3602 [View Article][PubMed]
    [Google Scholar]
  13. Kattenhorn L. M., Korbel G. A., Kessler B. M., Spooner E., Ploegh H. L. 2005; A deubiquitinating enzyme encoded by HSV-1 belongs to a family of cysteine proteases that is conserved across the family Herpesviridae. Mol Cell 19:547–557 [View Article][PubMed]
    [Google Scholar]
  14. Koonin E. V., Gorbalenya A. E., Purdy M. A., Rozanov M. N., Reyes G. R., Bradley D. W. 1992; Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: delineation of an additional group of positive-strand RNA plant and animal viruses. Proc Natl Acad Sci U S A 89:8259–8263 [View Article][PubMed]
    [Google Scholar]
  15. Lindner H. A., Fotouhi-Ardakani N., Lytvyn V., Lachance P., Sulea T., Ménard R. 2005; The papain-like protease from the severe acute respiratory syndrome coronavirus is a deubiquitinating enzyme. J Virol 79:15199–15208 [View Article][PubMed]
    [Google Scholar]
  16. Magden J., Takeda N., Li T., Auvinen P., Ahola T., Miyamura T., Merits A., Kääriäinen L. 2001; Virus-specific mRNA capping enzyme encoded by hepatitis E virus. J Virol 75:6249–6255 [View Article][PubMed]
    [Google Scholar]
  17. Malakhova O. A., Kim K. I., Luo J.-K., Zou W., Kumar K. G., Fuchs S. Y., Shuai K., Zhang D. E. 2006; UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity. EMBO J 25:2358–2367 [View Article][PubMed]
    [Google Scholar]
  18. Reyes-Turcu F. E., Horton J. R., Mullally J. E., Heroux A., Cheng X., Wilkinson K. D. 2006; The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of unanchored ubiquitin. Cell 124:1197–1208 [View Article][PubMed]
    [Google Scholar]
  19. Reyes-Turcu F. E., Ventii K. H., Wilkinson K. D. 2009; Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu Rev Biochem 78:363–397 [View Article][PubMed]
    [Google Scholar]
  20. Ropp S. L., Tam A. W., Beames B., Purdy M., Frey T. K. 2000; Expression of the hepatitis E virus ORF1. Arch Virol 145:1321–1337 [View Article][PubMed]
    [Google Scholar]
  21. Schlieker C., Korbel G. A., Kattenhorn L. M., Ploegh H. L. 2005; A deubiquitinating activity is conserved in the large tegument protein of the herpesviridae. J Virol 79:15582–15585 [View Article][PubMed]
    [Google Scholar]
  22. Sehgal D., Thomas S., Chakraborty M., Jameel S. 2006; Expression and processing of the hepatitis E virus ORF1 nonstructural polyprotein. Virol J 3:38 [View Article][PubMed]
    [Google Scholar]
  23. Skaug B., Chen Z. J. 2010; Emerging role of ISG15 in antiviral immunity. Cell 143:187–190 [View Article][PubMed]
    [Google Scholar]
  24. Tam A. W., Smith M. M., Guerra M. E., Huang C. C., Bradley D. W., Fry K. E., Reyes G. R. 1991; Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome. Virology 185:120–131 [View Article][PubMed]
    [Google Scholar]
  25. Wang J., Loveland A. N., Kattenhorn L. M., Ploegh H. L., Gibson W. 2006; High-molecular-weight protein (pUL48) of human cytomegalovirus is a competent deubiquitinating protease: mutant viruses altered in its active-site cysteine or histidine are viable. J Virol 80:6003–6012 [View Article][PubMed]
    [Google Scholar]
  26. Welchman R. L., Gordon C., Mayer R. J. 2005; Ubiquitin and ubiquitin-like proteins as multifunctional signals. Nat Rev Mol Cell Biol 6:599–609 [View Article][PubMed]
    [Google Scholar]
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