title: Evidence for positive selection in the extracellular domain of human cytomegalovirus encoded G protein-coupled receptor US28.
abstract: The human cytomegalovirus (HCMV)-encoded chemokine receptor US28 is also a seven-transmembrane G-protein coupled receptor, whose signaling pathway is known for its involvement in host immune system evasion. HCMV infection can result in serious disease in immunocompromised individuals and is also linked to atherosclerosis and cardiovascular disease. Identifying amino acid residues that play a crucial role in successful viral adaptation in response to the host's immune defense is critical for effective drug design. In this study maximum likelihood-based codon substitution analyses were carried out to determine whether any codon of US28 has evolved adaptively. If the rate of nonsynonymous (dn) to the rate of synonymous (ds) nucleotide substitutions (ω = dn/ds) is greater than one, the codon is said to be under positive selection, indicating adaptive evolution. Although the overall ω for US28 gene was 0.154, indicating that most codon sites were subject to strong purifying selection, five codon sites are under strong positive selection. Three (E18D/L, D19A/E/G, and R267K/Q) of these positively selected sites are located in extracellular domains, the domains that play a crucial role for successful viral adaptation in response to the host's immune defense. The C-terminal (R329Q/W) and the fifth transmembrane domain (V190I), each have one positively selected site. These results suggest that relative to the extracellular domains, amino acid residues present in intracellular domains are more selectively constrained. A few amino acid residues in extracellular domains of US28 evolved more rapidly, presumably due to positive selection pressure resulting from ligand-binding and pathogen interactions of extracellular domains.
authors.affiliation: College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Gong
authors.forename: Abinash
authors.initials: A
authors.lastname: Padhi
mesh_terms: D000595:Amino Acid Sequence; D005075:Biological Evolution; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D002681:China; D003062:Codon / Q000737:chemistry; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D005060:Europe; D006678:HIV / Q000254:growth & development; D015658:HIV Infections / Q000473:pathology / Q000821:virology; D006801:Humans; D057131:Immune Evasion / Q000235:genetics; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic / Q000276:immunology; D017434:Protein Structure, Tertiary; D019707:Receptors, Chemokine / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012641:Selection, Genetic; D015398:Signal Transduction / Q000235:genetics; D014481:United States; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; D003062:Codon; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C411191:US28 receptor, Cytomegalovirus; D014764:Viral Proteins; C450520:seven-transmembrane G-protein-coupled receptor