RT Journal Article SR Electronic(1) A1 Prod'homme, Virginie A1 Sugrue, Daniel M. A1 Stanton, Richard J. A1 Nomoto, Akio A1 Davies, James A1 Rickards, Carole R. A1 Cochrane, Daniel A1 Moore, Melanie A1 Wilkinson, Gavin W. G. A1 Tomasec, PeterYR 2010 T1 Human cytomegalovirus UL141 promotes efficient downregulation of the natural killer cell activating ligand CD112 JF Journal of General Virology, VO 91 IS 8 SP 2034 OP 2039 DO https://doi.org/10.1099/vir.0.021931-0 PB Microbiology Society, SN 1465-2099, AB 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., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.021931-0