PMID- 16014907 OWN - NLM STAT- MEDLINE DCOM- 20050818 LR - 20181113 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 79 IP - 15 DP - 2005 Aug TI - Variant-specific tropism of human herpesvirus 6 in human astrocytes. PG - 9439-48 AB - 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. FAU - Donati, Donatella AU - Donati D AD - Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Martinelli, Elena AU - Martinelli E FAU - Cassiani-Ingoni, Riccardo AU - Cassiani-Ingoni R FAU - Ahlqvist, Jenny AU - Ahlqvist J FAU - Hou, Jean AU - Hou J FAU - Major, Eugene O AU - Major EO FAU - Jacobson, Steve AU - Jacobson S LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Virol JT - Journal of virology JID - 0113724 SB - IM MH - Astrocytes/*virology MH - Cells, Cultured MH - Cytopathogenic Effect, Viral MH - Herpesvirus 6, Human/growth & development/*physiology MH - Humans MH - Roseolovirus Infections/*virology MH - Species Specificity MH - Virus Cultivation PMC - PMC1181567 EDAT- 2005/07/15 09:00 MHDA- 2005/08/19 09:00 PMCR- 2005/08/01 CRDT- 2005/07/15 09:00 PHST- 2005/07/15 09:00 [pubmed] PHST- 2005/08/19 09:00 [medline] PHST- 2005/07/15 09:00 [entrez] PHST- 2005/08/01 00:00 [pmc-release] AID - 79/15/9439 [pii] AID - 0252-05 [pii] AID - 10.1128/JVI.79.15.9439-9448.2005 [doi] PST - ppublish SO - J Virol. 2005 Aug;79(15):9439-48. doi: 10.1128/JVI.79.15.9439-9448.2005.