Human Herpesviruses at Sixes, Sevens, and More

In the past decade, the family circle of human herpesviruses (HHVs) has expanded to include three new numbers: HHV-6, −7,and −8.Although each was initially discovered in adults, their reputation, relevance, and renitence begin in infancy.

Techniques developed to study HIV infection revealed the existence of HHV-6. Initially found in the lymphocytes of patients with AIDS and lymphoproliferative diseases, this novel virus bore a familial resemblance to the herpesviruses and was adopted as their sixth member [1]. Composed of a large double-stranded DNA, DNA polymerase (but not thymidine kinase), and several important glycoproteins, HHV-6 can infect many types of cell but, like HIV, primarily affects CD4 cells. As with other herpesviruses, persistence or latency occurs; genomic material can then be detected in peripheral blood lymphocytes, secretions, and cerebrospinal fluid in healthy and immunosuppressed persons.

Human herpesvirus-6 actually comprises nearly identical twins, HHV-6A and HHV-6B. The genomic homogeneity of these variants is about 95%, but they differ in antigenicity; cell tropism; epidemiology; and, possibly, pathogenicity [2]. Human herpesvirus-6A was isolated first, and A strains have been recovered primarily from adults, especially immunosuppressed patients. Overall, however, HHV-6B isolates predominate. Human herpesvirus-6B is essentially the sole variant isolated from children with primary infection, and a direct causal relation with disease has been established for the B variant [2-4]. In adults, the quandary is whether the presence of HHV-6 is latent or causes disease. Adding to the mystery is the paucity of reports to date of primary infection with variant A.

The many miens and mimicries of HHV-6 are just beginning to be recognized. Seroepidemiologic studies quickly indicated universal acquisition during infancy: All newborns possess maternally derived antibody to HHV-6 that decreases to a nadir after several months [4]. This is followed by natural infection that proceeds over the next few …