Cytomegalovirus: Genetic Variation of Viral Genomes*

Genomic complexity of human CMV is one of the largest among various DNA viruses. With such genome complexity and widespread distribution, even a minimal frequency of mutation will be enough to create a complicated genetic heterogeneity in this virus. The virus genome is relatively stable during subcultivation in tissue culture. Variants with minor modification in restriction enzyme sites do gradually develop. These variants share substantial restriction fragment pattern homology with the parental virus. Virus DNA has a molecular weight of 150 X 10(6) daltons for a complete genome. The DNA contains 2 covalently linked L and S components which are separated by internal inverted repetitious sequences of both terminal-end sequences. L and S components are oriented invertably with 4 isomeric arrangements. No tandem repeated sequences have been found. Based on DNA restriction pattern analysis, we conclude that the majority of recurrent infections represent reactivation of existing latent viruses; however, reinfections by a new virus strain do occur occasionally. By studying virus strains isolated from the consecutive congenitally infected infants and strains from mothers and their congenitally infected offspring, we furthermore conclude that the latent virus in women is relatively stable genetically. Moreover, the virus strains after being transmitted to the offspring are still genetically similar to that of the mothers. As in vitro, spontaneous minor variations occur after the in vivo residence. In a long period of evolution the accumulation of minor variations might create great diversity with major similarity.