Differential tropism of human herpesvirus 6 (HHV-6) variants and induction of latency by HHV-6A in oligodendrocytes.
Human herpesvirus 6 (HHV-6) is a ubiquitous beta -herpesvirus associated with a number of clinical disorders. Two closely but biologically distinct variants have been described. HHV-6 variant B causes the common childhood disease exhanthem subitum, and although the pathologic characteristics for HHV-6 variant A are less well defined, HHV-6A has been suggested to be more neurotropic. We studied the effect of both HHV-6 variants in an oligodendrocyte cell line (MO3.13). Infection of M03.13 was monitored by cytopathic effect (CPE), quantitative TaqMan PCR for viral DNA in cells and supernatant, reverse transcriptase-polymerase chain reaction (RT-PCR) to detect viral RNA, and indirect immunofluorescence (IFA) to detect viral protein expression. HHV-6A infection induced significantly more CPE than infection with HHV-6B. HHV-6B induced an abortive infection associated with a decrease of the initial viral DNA load over time, early RNA expression, and no expression of viral antigen. In contrast, infection with HHV-6A DNA persisted in cells for at least 62 days. During the acute phase of infection with HHV-6A, intracellular and extracellular viral load increased and cells expressed the viral protein IE-2 and gp116/54/64. No HHV-6A RNA or protein was expressed after 30 days post infection, suggesting that HHV-6A formed a latent infection. These studies provide in vitro support to the hypothesis that HHV-6 can actively infect oligodendrocytes. Our results suggest that HHV-6A and HHV-6B have different tropism in MO3.13 cells and that an initially active HHV-6A infection can develop latency. Differences between HHV-6A and -6B infection in different neural cell types may be associated with different neurological diseases.
Ahlqvist
Jenny
J
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Fotheringham
Julie
J
Akhyani
Nahid
N
Yao
Karen
K
Fogdell-Hahn
Anna
A
Jacobson
Steven
S
D000956:Antigens, Viral / Q000235:genetics; D002460:Cell Line; D018792:Encephalitis, Viral / Q000473:pathology / Q000821:virology; D005077:Exanthema Subitum / Q000473:pathology / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D015654:Herpesvirus 6, Human / Q000235:genetics* / Q000254:growth & development*; D006801:Humans; D009103:Multiple Sclerosis / Q000473:pathology / Q000821:virology; D009836:Oligodendroglia / Q000473:pathology / Q000821:virology*; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology; D017735:Virus Latency
D000956:Antigens, Viral; D012333:RNA, Messenger