Persistence of Human Herpesvirus 6 According to Site and Variant: Possible Greater Neurotropism of Variant A

Abstract

Little is known of the persistence and pathogenicity of human herpesvirus 6 (HHV-6) after primary infection, including the role of strain variant. Over 2 to 5 years, 2,716 children and 149 families were studied. Peripheral blood mononuclear cell (PBMC), saliva, and cerebrospinal fluid (CSF) specimens were examined for HHV-6 DNA and variant. Ninety-nine percent of isolates causing primary infection were HHV-6 variant B (HHV-6B), which predominated in 95%-98% of the variants persisting in PBMC and saliva specimens from children and adults. Of 668 CSF samples, 13% contained HHV-6 DNA; of 77 children examined after primary infection, 61% had HHV-6 DNA detected only in their CSF and 39% had HHV-6 DNA in both CSF and PBMCs. HHV-6 variant A (HHV-6A) was detected significantly (P = .0001) more frequently in CSF than in PBMCs or saliva. In children for whom HHV-6 was identified in both CSF and PBMCs, PBMCs contained only HHV-6B, while CSF contained HHV-6A or HHV-6B, not both. Thus, in patients with dual infection, only HHV-6A persisted in CSF, which suggests that HHV-6A has greater neurotropism. Findings for adults indicate that dual infection occurs; variant persistence is similar to that for children. The frequency of HHV-6A infection increased little with age, thereby indicating that HHV-6A infection remains uncommon into adulthood. This study suggests that HHV-6 variants have different immunobiologic courses and neurotropism.

Diagnosis of human herpesvirus 6B primary infection by polymerase chain reaction in young children with exanthematic disease

“…In the 1990s, several authors proposed that following the primary infection, HHV-6 is shed in saliva chronically or intermittently, in disagreement with the present results that indicated low levels of HHV-6 in the saliva studied [14][15][16] . These low rates of detection lead our group to verify the sensitivity and specificity parameters, in order to compare the PCR performed here to the gold-standard diagnosis assay available: the immunofluorescence assay.…”

Identification and Characterization of U83A Viral Chemokine, a Broad and Potent β-Chemokine Agonist for Human CCRs with Unique Selectivity and Inhibition by Spliced Isoform

“…Both HHV-6A and HHV-6B have cellular tropisms for CD4 ϩ T lymphocytes, and both are neurotropic, although there may be differences in the exact site of latency, given the more disperse detection of HHV-6A where studies have been undertaken. Recent studies further support an enhanced neurotropism of HHV-6A strains, suggesting sequence differences may affect biology and pathogenesis (12)(13)(14). Interestingly, the chemokine encoded by HHV-6 is one of the few hypervariable genes, with up to 15% sequence differences between these strain variant groups and thus would be a major candidate for determining pathogenic differences.…”

“…strains identified to date, for example, in lung and neuronal tissue (12,13,36). The CCR4/CCR8 phenotype of Th2 cells also could contribute to the well-defined cellular tropism of HHV-6 for mature CD4 ϩ T lymphocytes (37) in chemoattracting this cellular population for lytic infection, whereas all of the reactive receptors are present on T lymphocytes.…”

Restriction of human herpesvirus 6B replication by p53

“…However, additional receptors for both HHV-6A and -6B are likely, as the two variants have different tropisms, and also appear to have distinct epidemiological and biological properties (Braun et al, 1997;Donati et al, 2005;Hall et al, 1998;Pedersen & Höllsberg, 2006). Upon infection, HHV-6B blocks host-cell DNA replication (Di Luca et al, 1990) within the first 12 h in T cells (Øster et al, 2005).…”