Sequence analysis of human cytomegalovirus US28 gene in low-passage clinical isolates from children and AIDS patients
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Human cytomegalovirus (HCMV) is often a dangerous opportunistic pathogen that causes significant morbidity and mortality in newborn children and immunocompromised patients. The different symptoms and tissue tropisms of HCMV infection may result from genetic polymorphism. This study investigated the sequence variability of the HCMV US28 ORF, which shows sequence homology to the G protein-coupled receptor. HCMV isolated from suspected pediatric cases and isolates from AIDS patients were compared in order to examine the possible associations between polymorphisms and pathogenesis. Seventy children with suspected congenital HCMV infection, who suffered from jaundice (47), megacolon (10), and microcephaly (13), and 17 AIDS patients, were studied. Mutation was prevalent among the sequences of US28, with a focus on the two ends of US28. The important functional groups of US28 are highly conserved. An unrooted tree showed that all sequences from suspected congenitally infected infants and AIDS patients were divided into three groups. Comparison showed that most of the sequences (12/17) from pediatric patients were included in the first group (G1), whereas most of the sequences (11/17) from AIDS patients were included in the third group (G3). The specific high mutation sites in US28 from children were located at the C terminus of the protein, whereas those from AIDS patients were located at the N terminus. We demonstrated the existence of polymorphisms among the US28 genes of clinical isolates of HCMV from infants with suspected congenital infection. Comparison of US28 sequences from AIDS patients with those from children showed that both sequences have their own specific high mutation points.
- Arav-Boger R, Willoughby R, Pass R, Zong J, Jang W, Alcendor D, Hayward G (2002) Polymorphisms of the cytomegalovirus (CMV)-encoded tumor necrosis factor-alpha and beta-chemokine receptors in congenital CMV disease. J Infect Dis 186: 1057-1064.
- Baldanti F, Sarasini A, Furione M, Gatti M, Comolli G, Revello MG, Gerna G (1998) Coinfection of the immunocompromised but not the immunocompetent host by multiple human cytomegalovirus strains. Arch Virol 143: 1701-1709.
- Bale JF, Petheram SJ, Robertson M, Murph JR, Demmler G (2001) Human cytomegalovirus a sequence and UL144 variability in strains from infected children. J Med Virol 65: 90-96.
- Beisser PS, Goh CS, Cohen FE, Michelson S (2002) Viral chemokine receptors and chemokines in human cytomegalovirus trafficking and interaction with the immune system. CMV chemokine receptors. Curr Top Microbiol Immunol 269: 203-234.
- Benedict CA, Butrovich KD, Lurain NS, Corbeil J, Rooney I, Schneider P, Tschopp J, Ware CF (1999) Cutting edge: a novel viral TNF receptor superfamily member in virulent strains of human cytomegalovirus. J Immunol 162: 6967-6970.
- Billstrom MA, Johnson GL, Avdi NJ, Worthen GS (1998) Intracellular signaling by the chemokine receptor US28 during human cytomegalovirus infection. J Virol 72: 5535-5544.
- Bodaghi B, Jones TR, Zipeto D, Vita C, Sun L, Laurent L, Arenzana-Seisdedos F, Virelizier JL, Michelson S (1998) Chemokine sequestration by viral chemoreceptors as a novel viral escape strategy: withdrawal of chemokines from the environment of cytomegalovirus-infected cells. J Exp Med 188: 855-866.
- Casarosa P, Bakker RA, Verzijl D, Navis M, Timmerman H, Leurs R, Smit MJ (2001) Constitutive signaling of the human cytomegalovirus-encoded chemokine receptor US28. J Biol Chem 276: 1133-1137.
- Chen R, Xiong S, Yang Y, Fu W, Wang Y, Ge J (2003) The relationship between human cytomegalovirus infection and atherosclerosis development. Mol Cell Biochem 249: 91-96.
- Demmler GJ (1991) Infectious Diseases Society of America and Centers for Disease Control. Summary of a workshop on surveillance for congenital cytomegalovirus disease. Rev Infect Dis 13: 315-329.
- Gao JL, Murphy PM (1994) Human cytomegalovirus open reading frame US28 encodes a functional beta chemokine receptor. J Biol Chem 269: 28539-28542.
- Goffard A, Gault E, Rozenberg F, Moret N, Hober D, Dény P (2006) Comparative sequence analysis of US28 gene of human cytomegalovirus strains isolated from HIV-positive patients. Virus Genes 33: 175-181.
- He R, Ruan Q, Qi Y, Ma YP, Huang YJ, Sun ZR, Ji YH (2006) Sequence variability of human cytomegalovirus UL146 and UL147 genes in low-passage clinical isolates. Intervirology 49: 215-223.
- Hendrix MG, Daemen M, Bruggeman CA (1991) Cytomegalovirus nucleic acid distribution within the human vascular tree. Am J Pathol 138: 563-567.
- Ho M (1990) Epidemiology of cytomegalovirus infections. Rev Infect Dis 12 (Suppl 7): S701-S710.
- Kuhn DE, Beall CJ, Kolattukudy PE (1995) The cytomegalovirus US28 protein binds multiple CC chemokines with high affinity. Biochem Biophys Res Commun 211: 325-330.
- Lurain NS, Kapell KS, Huang DD, Short JA, Paintsil J, Winkfield E, Benedict CA, Ware CF, Bremer JW (1999) Human cytomegalovirus UL144 open reading frame: sequence hypervariability in low-passage clinical isolates. J Virol 73: 10040-10050.
- Macris MP, Nahmias AJ, Bailey PD, Lee FK, Visintine AM, Brann AW (1981) Electron microscopy in the routine screening of newborns with congenital cytomegalovirus infection. J Virol Methods 2: 315-320.
- Miller DM, Espinosa-Heidmann DG, Legra J, Dubovy SR, Sũner IJ, Sedmak DD, Dix RD, Cousins SW (2004) The association of prior cytomegalovirus infection with neovascular age-related macular degeneration. Am J Ophthalmol 138: 323-328.
- Nerheim PL, Meier JL, Vasef MA, Li WG, Hu L, Rice JB, Gavrila D, Richenbacher WE, Weintraub NL (2004) Enhanced cytomegalovirus infection in atherosclerotic human blood vessels. Am J Pathol 164: 589-600.
- Picone O, Costa J, Chaix M, Ville Y, Rouzioux C, Leruez-Ville M (2005) Human cytomegalovirus UL144 gene polymorphisms in congenital infections. J Clin Microbiol 43: 25-29.
- Pignatelli S, Dal Monte P, Rossini G, Landini MP (2004) Genetic polymorphisms among human cytomegalovirus (HCMV) wild-type strains. Rev Med Virol 14: 383-410.
- Pleskoff O, Tréboute C, Brelot A, Heveker N, Seman M, Alizon M (1997) Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry. Science 276: 1874-1878.
- Pleskoff O, Tréboute C, Alizon M (1998) The cytomegalovirus-encoded chemokine receptor US28 can enhance cell-cell fusion mediated by different viral proteins. J Virol 72: 6389-6397.
- Rasmussen L, Geissler A, Winters M (2003) Inter- and intragenic variations complicate the molecular epidemiology of human cytomegalovirus. J Infect Dis 187: 809-819.
- Staak K, Prosch S, Stein J, Priemer C, Ewert R, Docke WD, Kruger DH, Volk HD, Reinke P (1997) Pentoxifylline promotes replication of human cytomegalovirus in vivo and in vitro. Blood 89: 3682-3690.
- Streblow DN, Soderberg-Naucler C, Vieira J, Smith P, Wakabayashi E, Ruchti F, Mattison K, Altschuler Y, Nelson JA (1999) The human cytomegalovirus chemokine receptor US28 mediates vascular smooth muscle cell migration. Cell 99: 511-520.
- Tam PK, Quint WG, van Velzen D (1992) Hirschsprung's disease: a viral etiology? Pediatr Pathol 12: 807-810.
- Valantine HA (2004) The role of viruses in cardiac allograft vasculopathy. Am J Transplant 4: 169-177.
- Vieira J, Schall TJ, Corey L, Geballe AP (1998) Functional analysis of the human cytomegalovirus US28 gene by insertion mutagenesis with the green fluorescent protein gene. J Virol 72: 8158-8165.
- Vischer HF, Leurs R, Smit MJ (2006) HCMV-encoded G-protein-coupled receptors as constitutively active modulators of cellular signaling networks. Trends Pharmacol Sci 27: 56-63.
- Waldhoer M, Casarosa P, Rosenkilde MM, Smit MJ, Leurs R, Whistler JL, Schwartz TW (2003) The carboxyl terminus of human cytomegalovirus-encoded 7 transmembrane receptor US28 camouflages agonism by mediating constitutive endocytosis. J Biol Chem 278: 19473-19482.
- Wang A, Ren L, Abenes G, Hai R (2009) Genome sequence divergences and functional variations in human cytomegalovirus strains. FEMS Immunol Med Microbiol 55: 23-33.
- Wu TC, Hruban RH, Ambinder RF, Pizzorno M, Cameron DE, Baumgartner WA, Reitz BA, Hayward GS, Hutchins GM (1992) Demonstration of cytomegalovirus nucleic acids in the coronary arteries of transplanted hearts. Am J Pathol 140: 739-747.
- Zipeto D, Bodaghi B, Laurent L, Virelizier JL, Michelson S (1999) Kinetics of transcription of human cytomegalovirus chemokine receptor US28 in different cell types. J Gen Virol 80 (Pt 3): 543-547.
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