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Journal of Virology, August 2005, p. 9439-9448, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9439-9448.2005

Variant-Specific Tropism of Human Herpesvirus 6 in Human Astrocytes

Donatella Donati ,^1,, Elena Martinelli,^1, Riccardo Cassiani-Ingoni,¹ Jenny Ahlqvist,^1, Jean Hou,² Eugene O. Major,² and Steve Jacobson^1*

Viral Immunology Section,¹ Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland²

Received 4 February 2005/ Accepted 20 April 2005

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.

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* Corresponding author. Mailing address: Bldg. 10, Room 5N214, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Phone: (301) 496-0519. Fax: (301) 402-0373. E-mail: jacobsons{at}ninds.nih.gov.

D.D. and E.M. equally contributed to this work.

Present address: Struttura Complessa di Microbiologia e Virologia, Azienda Ospedaliera Universitaria Senese, Siena, Italia.

Present address: Division of Neurology, Neurotec Department, Karolinska Institute at Karolinska University Hospital in Huddinge, Stockholm, Sweden.

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Journal of Virology, August 2005, p. 9439-9448, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9439-9448.2005

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