SEQUENCE VARIATION WITHIN NEUTRALIZING EPITOPES OF THE ENVELOPE GLYCOPROTEIN-B OF HUMAN CYTOMEGALOVIRUS - COMPARISON OF ISOLATES FROM RENAL-TRANSPLANT RECIPIENTS AND AIDS PATIENTS

The envelope glycoprotein B of human cytomegalovirus (CMV) is a major target of the neutralizing antibody response against this virus, and h ence has importance as a potential subunit vaccine. PCR was utilized t o amplify DNA encoding the dominant antigenic determinant on this mole cule, AD-1 (codons 552 to 635), and DNA sequencing was carried out in order to compare nucleotide variation in AD-1 between clinical isolate s of CMV and die laboratory strain AD 1 69. Wild-type CMV strains isol ated from AIDS patients were not only more likely to possess nucleotid e substitutions (19/24 compared to 5/25, P < 0.0001) than those from r enal transplant recipients, but they also exhibited a greater degree o f nucleotide sequence divergence (6-94 versus 0.82 substitutions/1000 bp, P < 0-0001; 96-0 to 100 % versus 99.4 to 100 % similarity). Increa sed sequence variation in the AIDS patients did not correlate with abs olute peripheral blood CD4+ T cell level (r = 0.33, P > 0.1). Only two strains from AIDS patients and one strain from the renal transplant r ecipients possessed nucleic acid substitutions that resulted in codon changes, indicating that AD-1 is relatively well conserved amongst cli nical isolates of CMV. The demonstration of strains with codon changes within neutralizing epitopes, however, highlights the importance of t aking into consideration the presence of these strains within the wild -type virus population when preparing subunit vaccines.