DNA of human cytomegalovirus: size heterogeneity and defectiveness resulting from serial undiluted passage.

The majority of DNA molecules associated with plaque-purified, low-multiplicity-passaged human cytomegalovirus (Towne strain) had a molecular weight of approximately 150 x 10(6) and a molecular complexity of approximately 140 x 10(6). Serial high-multiplicity passage resulted in the production of defective cytomegalovirions. An accumulation of smaller DNA molecules packaged into virions was directly correlated with a decrease in infectivity and an increase in the particle-to-PFU ratio. The majority of defective DNA molecules had a molecular weight of approximately 100 x 10(6). In addition, there were some viral DNA molecules of approximately 60 x 10(6). Restriction enzyme analysis of defective cytomegalovirus DNA detected unique DNA fragments, suggesting a specific alteration in the nucleotide sequence. Some reasons for the generation of defective cytomegalovirus DNA are discussed.