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 (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.
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 (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.
Authors: Clemens Warnke; Til Menge; Hans-Peter Hartung; Michael K Racke; Petra D Cravens; Jeffrey L Bennett; Elliot M Frohman; Benjamin M Greenberg; Scott S Zamvil; Ralf Gold; Bernhard Hemmer; Bernd C Kieseier; Olaf Stüve Journal: Arch Neurol Date: 2010-08
Authors: Til Menge; Martin S Weber; Bernhard Hemmer; Bernd C Kieseier; Hans-Christian von Büdingen; Clemens Warnke; Scott S Zamvil; Aaron Boster; Omar Khan; Hans-Peter Hartung; Olaf Stüve Journal: Drugs Date: 2008 Impact factor: 9.546
Authors: Martin S Weber; Mahdia Benkhoucha; Klaus Lehmann-Horn; Deetje Hertzenberg; Johann Sellner; Marie-Laure Santiago-Raber; Michel Chofflon; Bernhard Hemmer; Scott S Zamvil; Patrice H Lalive Journal: PLoS One Date: 2010-12-30 Impact factor: 3.240