Comparative sequence analysis of US28 gene of human cytomegalovirus strains isolated from HIV-positive patients.

Human Cytomegalovirus (HCVM) encodes several G-protein coupled receptors, such as US28 protein. We determined the US28 gene sequence from clinical isolates obtained from 17 Human Immunodeficiency Virus (HIV)-infected patients with HCMV infection. Two types of clinical specimens were collected: peripheral blood leucocytes (PBLs) from 12 patients with HCMV-positive viremia and cerebro-spinal fluids (CSF) from five patients with HCMV-encephalitis. Comparison of US28 nucleotide sequences between clinical specimens and several HCMV reference strains showed that mutations were clustered at both ends of the gene. The mutations observed at the C-terminus were observed at some sequences whereas the mutations observed at the N-terminus lead us to define five patterns of mutations. These patterns were equally distributed among isolates obtained from CSF or PBLs of HIV-infected patients. For each clinical isolate, the gB genotype was determined. There was no genetic association between gB genotype and US28 patterns. The comparison of the results of the present study and those published from sequences obtained from children with HCMV congenital disease (Arav-Boger, 2002) demonstrates that two motifs appear especifically either in US28 protein sequences obtained from HIV-positive patients (motif 4) or in US28 protein sequences obtained from patients with congenital HCMV infection (motif 5/genotype B). The appearance of these patterns of mutations in other clinical context needs to be studied.