Detection of human cytomegalovirus and analysis of strain variation.

Human cytomegalovirus (CMV) is increasingly recognized as an important human pathogen (43). This virus produces a series of clinical pictures varying from classic "Scytomegalic inclusion disease" to intrauterine death, prematurity, congential defects, infectious mononucleosis, postperfusion syndrome, and interstitial pneumonia in patients who have undergone organ transplantation (29, 43). It is likely that other diseases or syndromes caused by human cytomegalovirus have not yet been recognized. The observations that human CMV may cause normal human fibroblast cells to multiply and grow in soft agarose (28) and that human CMV has the ability to transform hamster-embryo fibroblasts (1) suggest that human CMV might have oncogenic potency comparable to that of herpes simplex, Epstein-Barr virus (EBV), and other herpes-group viruses. Human CMV has been isolated from saliva, urine, blood, human milk, cervical secretions, various tissue specimens, and even from human semen (30, 43). In congenital and postnatal infections, the virus is excreted from saliva and urine for a sustained period and then apparently enters a latent state. Recurrence of excretion of CMV in pregnancy (31, E. R. Alexander, and our unpublished observations), reactivation of CMV replication in immunosuppressed patients (8), and the presence of infectious CMV in fresh donor bloods (7) strongly indicate the latency of human CMV infections as found with other herpes-group viruses. The peculiar thermal and chemical lability of human CMV, the slow appearance of cytopathic effects, the slow growth cycle in tissue culture and the remarkable antigenic variation, plus the lack of specific heterologous hyperimmune serum present complicating factors in the diagnosis of human CMV infection. In this communication we would like to discuss some of our new approaches for virus detection, as well as the study of strain differences as approached by nucleic acid hybridization, restriction endonuclease analyses of the CMV genome, and antigenic analyses.