Variant-specific tropism of human herpesvirus 6 in human astrocytes.
Though first described as a lymphotropic virus, human herpesvirus 6 (HHV-6) is highly neuropathogenic. Two viral variants are known: HHV-6A and HHV-6B. Both variants can infect glial cells and have been differentially associated with central nervous system diseases, suggesting an HHV-6 variant-specific tropism for glial cell subtypes. We have performed infections with both viral variants in human progenitor-derived astrocytes (HPDA) and monitored infected cell cultures for cytopathic effect (CPE), intra- and extracellular viral DNA load, the presence of viral particles by electronic microscopy, mRNA transcription, and viral protein expression. HHV-6A established a productive infection with CPE, visible intracellular virions, and high virus DNA loads. HHV-6B-infected HPDA showed no morphological changes, intracellular viral particles, and decreasing intra- and extracellular viral DNA over time. After long-term passage, HHV-6B-infected HPDA had stable but low levels of intracellular viral DNA load with no detectable viral mRNA. Our results demonstrate that HHV-6A and HHV-6B have differential tropisms and patterns of infection for HPDA in vitro, where HHV-6A results in a productive lytic infection. In contrast, HHV-6B was associated with a nonproductive infection. These findings suggest that HHV-6 variants might be responsible for specific infection patterns in glial cells in vivo. Astrocytes may be an important reservoir for this virus in which differential tropism of HHV-6A and HHV-6B may be associated with different disease outcomes.
Donati
Donatella
D
Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Martinelli
Elena
E
Cassiani-Ingoni
Riccardo
R
Ahlqvist
Jenny
J
Hou
Jean
J
Major
Eugene O
EO
Jacobson
Steve
S
D001253:Astrocytes / Q000821:virology*; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D015654:Herpesvirus 6, Human / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D019349:Roseolovirus Infections / Q000821:virology*; D013045:Species Specificity; D014776:Virus Cultivation