Apoptotic effects of Human Herpesvirus-6A on glia and neurons as potential triggers for central nervous system autoimmunity

doi:10.1016/S1386-6532(06)70005-1

Journal of Clinical Virology

Volume 37, Supplement 1, December 2006, Pages S11-S16

https://doi.org/10.1016/S1386-6532(06)70005-1 Get rights and content

Abstract

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.

Objectives

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).

Study design

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 (5×10⁴ cells target cells and 2×10⁶ 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.

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Apoptotic effects of Human Herpesvirus-6A on glia and neurons as potential triggers for central nervous system autoimmunity

Abstract

Background

Objectives

Study design

Results

Conclusions

J Biol Chem

Lancet

Lancet

Virology

J Neuroimmunol

Cell

Human herpesvirus 6: An emerging pathogen

Emerg Infect Dis

HHV-6 infects human aortic and heart microvascular endothelial cells, increasing their ability to secrete proinflammatory chemokines

J Med Virol

Plaque-associated expression of human herpesvirus 6 in multiple sclerosis

Proc Natl Acad Sci USA

HHV-6 and multiple sclerosis

Nat Med