Human cytomegalovirus UL18 utilizes US6 for evading the NK and T-cell responses.
| Autor: | Youngkyun Kim, Boyoun Park, Sunglim Cho, Jinwook Shin, Kwangmin Cho, Youngsoo Jun, Kwangseog Ahn |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: | |
| Zdroj: | PLoS Pathogens, Vol 4, Iss 8, p e1000123 (2008) |
| Druh dokumentu: | article |
| ISSN: | 1553-7366 1553-7374 |
| DOI: | 10.1371/journal.ppat.1000123 |
| Popis: | Human cytomegalovirus (HCMV) US6 glycoprotein inhibits TAP function, resulting in down-regulation of MHC class I molecules at the cell surface. Cells lacking MHC class I molecules are susceptible to NK cell lysis. HCMV expresses UL18, a MHC class I homolog that functions as a surrogate to prevent host cell lysis. Despite a high level of sequence and structural homology between UL18 and MHC class I molecules, surface expression of MHC class I, but not UL18, is down regulated by US6. Here, we describe a mechanism of action by which HCMV UL18 avoids attack by the self-derived TAP inhibitor US6. UL18 abrogates US6 inhibition of ATP binding by TAP and, thereby, restores TAP-mediated peptide translocation. In addition, UL18 together with US6 interferes with the physical association between MHC class I molecules and TAP that is required for optimal peptide loading. Thus, regardless of the recovery of TAP function, surface expression of MHC class I molecules remains decreased. UL18 represents a unique immune evasion protein that has evolved to evade both the NK and the T cell immune responses. |
| Databáze: | Directory of Open Access Journals |
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