This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.01961-06v1 81/5/2117    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, Q. Articles by Jung, J. U. Search for Related Content PubMed PubMed Citation Articles by Li, Q. Articles by Jung, J. U.

Downregulation of Gamma Interferon Receptor 1 by Kaposi's Sarcoma-Associated Herpesvirus K3 and K5

Department of Microbiology and Molecular Genetics, New England Regional Primate Research Center, Harvard Medical School, One Pine Hill Drive, Southborough, Massachusetts 01772,¹ Department of Pathology, Yale Medical School, New Haven, Connecticut 06520-8023²

Received 8 September 2006/ Accepted 27 November 2006

Upon viral infection, the major defense mounted by the host immune system is activation of the interferon (IFN)-mediated antiviral pathway. In order to complete their life cycles, viruses must modulate the host IFN-mediated immune response. The K3 and K5 proteins of a human tumor-inducing herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV), have been shown to downregulate the surface expression of host immune modulatory receptors by increasing their endocytosis rates, which leads to suppression of cell-mediated immunity. In this report, we demonstrate that K3 and K5 both specifically target gamma interferon receptor 1 (IFN-R1) and induce its ubiquitination, endocytosis, and degradation, resulting in downregulation of IFN-R1 surface expression and, thereby, inhibition of IFN- action. Mutational analysis indicated that K5 appeared to downregulate IFN-R1 more strongly than K3 and that the amino-terminal ring finger motif and the carboxyl-terminal region of K5 were necessary for IFN-R1 downregulation. These results suggest that KSHV K3 and K5 suppress both cytokine-mediated and cell-mediated immunity, which ensures efficient viral avoidance of host immune controls.

Published ahead of print on 13 December 2006.

This article has been cited by other articles:

• Cadwell, K., Coscoy, L. (2008). The Specificities of Kaposi's Sarcoma-Associated Herpesvirus-Encoded E3 Ubiquitin Ligases Are Determined by the Positions of Lysine or Cysteine Residues within the Intracytoplasmic Domains of Their Targets. J. Virol. 82: 4184-4189 [Abstract] [Full Text]  
• Thomas, M., Boname, J. M., Field, S., Nejentsev, S., Salio, M., Cerundolo, V., Wills, M., Lehner, P. J. (2008). Down-regulation of NKG2D and NKp80 ligands by Kaposi's sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity. Proc. Natl. Acad. Sci. USA 105: 1656-1661 [Abstract] [Full Text]  
• Randall, R. E., Goodbourn, S. (2008). Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 89: 1-47 [Abstract] [Full Text]  
• Lefort, S., Soucy-Faulkner, A., Grandvaux, N., Flamand, L. (2007). Binding of Kaposi's Sarcoma-Associated Herpesvirus K-bZIP to Interferon-Responsive Factor 3 Elements Modulates Antiviral Gene Expression. J. Virol. 81: 10950-10960 [Abstract] [Full Text]  
• Barriere, H., Nemes, C., Du, K., Lukacs, G. L. (2007). Plasticity of Polyubiquitin Recognition as Lysosomal Targeting Signals by the Endosomal Sorting Machinery. Mol. Biol. Cell 18: 3952-3965 [Abstract] [Full Text]  
• Kwun, H. J., da Silva, S. R., Shah, I. M., Blake, N., Moore, P. S., Chang, Y. (2007). Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mimics Epstein-Barr Virus EBNA1 Immune Evasion through Central Repeat Domain Effects on Protein Processing. J. Virol. 81: 8225-8235 [Abstract] [Full Text]