Structure, function and physiological consequences of virally encoded chemokine seven transmembrane receptors

Abstract

A number of human and animal herpes viruses encode G-protein coupled receptors with seven transmembrane (7TM) segments-most of which are clearly related to human chemokine receptors. It appears, that these receptors are used by the virus for immune evasion, cellular transformation, tissue targeting, and possibly for cell entry. In addition, many virally-encoded chemokine 7TM receptors have been suggested to be causally involved in pathogenic phenotypes like Kaposi sarcoma, atherosclerosis, HIV-infection and tumour development. The role of these receptors during the viral life cycle and in viral pathogenesis is still poorly understood. Here we focus on the current knowledge of structure, function and trafficking patterns of virally encoded chemokine receptors and further address the putative roles of these receptors in virus survival and host -cell and/or -immune system modulation. Finally, we highlight the emerging impact of these receptor on virus-mediated diseases.

Figure 1

Serpentine model of a rhodopsin-like 7TM chemokine receptor. Black circles with a white letter represent conserved residues in each helix. Residues important for binding of intracellular adaptor/scaffolding or signalling molecules are indicated in grey. Two generally accepted numbering systems for transmembrane-located residues in 7TM receptors are used: (i) the Schwartz-Baldwin (Baldwin, 1993; Schwartz, 1994) numbering system, where each residue is labelled according to its actual position within a transmembrane helix and (ii) the Ballesteros–Weinstein system, which is based on labelling a highly conserved position in each helix with the number 50 (Ballesteros and Weinstein, 1995). For instance, the conserved arginine in the ‘DRY' motif at the bottom of TM-3 is given the number III:26/3.50, according to the Schwartz/Ballesteros numbering systems, respectively. This figure was adapted from Schwartz and Holst (2003) with permission.

Figure 2

Herpesviruses encode one or more 7TM receptors that are expressed in host cells after viral infection. Some of these receptors act as a HIV co-receptor, whereas others might play a role in the progression of cardiovascular diseases or cancer.