The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome

The gene complement of wild-type human cytomegalovirus (HCMV) is incompletely understood, on account of the size and complexity of the viral genome and because laboratory strains have undergone deletions and rearrangements during adaptation to growth in culture. We have determined the sequence (241 087 bp) of chimpanzee cytomegalovirus (CCMV) and have compared it with published HCMV sequences from the laboratory strains AD169 and Toledo, with the aim of clarifying the gene content of wild-type HCMV. The HCMV and CCMV genomes are moderately diverged and essentially collinear. On the basis of conservation of potential protein-coding regions and other sequence features, we have discounted 51 previously proposed HCMV ORFs, modified the interpretations for 24 (including assignments of multiple exons) and proposed ten novel genes. Several errors were detected in the published HCMV sequences. We presently recognize 165 genes in CCMV and 145 in AD169; this compares with an estimate of 189 unique genes for AD169 made in 1990. Our best estimate for the complement of wild-type HCMV is 164 to 167 genes.