Apoptotic effects of Human Herpesvirus-6A on glia and neurons as potential triggers for central nervous system autoimmunity.
BACKGROUND
Human Herpesvirus type 6 (HHV-6A and/or HHV-6B) has been tentatively associated with multiple sclerosis (MS). However, there is currently no direct proof of pathogenicity.


OBJECTIVE
To determine whether exposure to HHV-6 variants is capable of inducing programmed cell death (apoptosis) in representative cell types of the central nervous system (CNS).


METHODS
HHV-6A and HHV-6B variants were grown on human T cell lines HSB2 and MOLT-3, respectively. Human neuronal (SK-N-SH), astrocytes (CRT), and oligodendrocytes (TC620) cell lines were exposed in vitro to infected T cells in a trans-well system for up to 4 days (5x10(4) cells target cells and 2x10(6) T cells). Apoptosis was measured by a FACS-based method.


RESULTS
Exposure to HHV-6A induced apoptosis in a time-dependent manner, while exposure to HHV-6B did not. Three days after exposure, apoptosis was increased compared to normalized controls, by 239% in neurons, 321% in astrocytes, and 326% in oligodendrocytes, respectively.


CONCLUSIONS
This study provides the demonstration that exposure to immune cells carrying replicating HHV-6A may injure glial cells and neurons by inducing apoptosis, and direct evidence for a causal association between HHV-6A with MS and related disorders.
Gardell
Jennifer L
JL
Department of Neurology, University of California, San Francisco, CA, USA.
Dazin
Paul
P
Islar
Janeen
J
Menge
Til
T
Genain
Claude P
CP
Lalive
Patrice H
PH
D017209:Apoptosis; D015551:Autoimmunity; D002460:Cell Line; D002490:Central Nervous System / Q000473:pathology*; D018920:Coculture Techniques; D005434:Flow Cytometry; D015654:Herpesvirus 6, Human / Q000472:pathogenicity*; D006801:Humans; D009457:Neuroglia / Q000473:pathology / Q000821:virology*; D009474:Neurons / Q000473:pathology / Q000821:virology*; D013601:T-Lymphocytes / Q000821:virology; D013997:Time Factors