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Human cytomegalovirus UL141 promotes efficient downregulation of the natural killer cell activating ligand CD112

Prod'homme, Virginie, Sugrue, Daniel M., Stanton, Richard James, Nomoto, A., Davies, James Anthony, Rickards, Carole R., Cochrane, Daniel, Moore, Melanie, Wilkinson, Gavin William Grahame and Tomasec, Peter 2010. Human cytomegalovirus UL141 promotes efficient downregulation of the natural killer cell activating ligand CD112. Journal of General Virology 91 (8) , pp. 2034-2039. 10.1099/vir.0.021931-0

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Abstract

Human cytomegalovirus (HCMV) UL141 induces protection against natural killer cell-mediated cytolysis by downregulating cell surface expression of CD155 (nectin-like molecule 5; poliovirus receptor), a ligand for the activating receptor DNAM-1 (CD226). However, DNAM-1 is also recognized to bind a second ligand, CD112 (nectin-2). We now show that HCMV targets CD112 for proteasome-mediated degradation by 48 h post-infection, thus removing both activating ligands for DNAM-1 from the cell surface during productive infection. Significantly, cell surface expression of both CD112 and CD155 was restored when UL141 was deleted from the HCMV genome. While gpUL141 alone is sufficient to mediate retention of CD155 in the endoplasmic reticulum, UL141 requires assistance from additional HCMV-encoded functions to suppress expression of CD112.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology
R Medicine > R Medicine (General)
Publisher: Society for General Microbiology
ISSN: 0022-1317
Last Modified: 28 Jun 2019 02:41
URI: http://orca.cf.ac.uk/id/eprint/29199

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