Human cytomegalovirus UL141 promotes efficient downregulation of the natural killer cell activating ligand CD112.
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.
Prod'homme
Virginie
V
Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
Sugrue
Daniel M
DM
Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
Stanton
Richard J
RJ
Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
Nomoto
Akio
A
Department of Microbiology, Graduate School of Medicine, University of Tokyo, Japan.
Davies
James
J
Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
Rickards
Carole R
CR
Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
Cochrane
Daniel
D
Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
Moore
Melanie
M
Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
Wilkinson
Gavin W G
GWG
Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
Tomasec
Peter
P
Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity*; D017353:Gene Deletion; D006801:Humans; D007108:Immune Tolerance; D053646:Interleukin-2 Receptor beta Subunit / Q000037:antagonists & inhibitors*; D007694:Killer Cells, Natural / Q000276:immunology*; D011991:Receptors, Virus / Q000037:antagonists & inhibitors; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D037521:Virulence Factors / Q000276:immunology / Q000502:physiology*
C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; D011991:Receptors, Virus; D014764:Viral Proteins; D037521:Virulence Factors; C066100:poliovirus receptor
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