Human cytomegalovirus encodes a highly specific RANTES decoy receptor.
The human cytomegalovirus pUL21.5 protein is a small, secreted glycoprotein whose mRNA is packaged into virions. We demonstrate that pUL21.5 protein is a soluble CC chemokine receptor that functions as a decoy to modulate the host immune response to infection. In contrast to other viral chemokine-binding proteins, which interact promiscuously with multiple chemokines, pUL21.5 selectively binds RANTES (regulated upon activation, normal T cell expressed and secreted) with high affinity. By binding RANTES, pUL21.5 blocks RANTES interaction with its cellular receptors. We propose that human cytomegalovirus directs the synthesis of a secreted, virus-coded protein that modulates the host antiviral response even before the newly infecting viral genome becomes transcriptionally active.
Wang
Dai
D
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Bresnahan
Wade
W
Shenk
Thomas
T
D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology; D006801:Humans; D019713:Receptors, CCR5; D019707:Receptors, Chemokine / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D014779:Virus Replication
D018946:Chemokine CCL5; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D014764:Viral Proteins