Herpesvirus trigger accelerates neuroinflammation in a nonhuman primate model of multiple sclerosis

EC Leibovitch, B Caruso, SK Ha… - Proceedings of the …, 2018 - National Acad Sciences
EC Leibovitch, B Caruso, SK Ha, MK Schindler, NJ Lee, NJ Luciano, BJ Billioux, JR Guy…
Proceedings of the National Academy of Sciences, 2018National Acad Sciences
Pathogens, particularly human herpesviruses (HHVs), are implicated as triggers of disease
onset/progression in multiple sclerosis (MS) and other neuroinflammatory disorders.
However, the time between viral acquisition in childhood and disease onset in adulthood
complicates the study of this association. Using nonhuman primates, we demonstrate that
intranasal inoculations with HHV-6A and HHV-6B accelerate an MS-like neuroinflammatory
disease, experimental autoimmune encephalomyelitis (EAE). Although animals inoculated …
Pathogens, particularly human herpesviruses (HHVs), are implicated as triggers of disease onset/progression in multiple sclerosis (MS) and other neuroinflammatory disorders. However, the time between viral acquisition in childhood and disease onset in adulthood complicates the study of this association. Using nonhuman primates, we demonstrate that intranasal inoculations with HHV-6A and HHV-6B accelerate an MS-like neuroinflammatory disease, experimental autoimmune encephalomyelitis (EAE). Although animals inoculated intranasally with HHV-6 (virus/EAE marmosets) were asymptomatic, they exhibited significantly accelerated clinical EAE compared with control animals. Expansion of a proinflammatory CD8 subset correlated with post-EAE survival in virus/EAE marmosets, suggesting that a peripheral (viral?) antigen-driven expansion may have occurred post-EAE induction. HHV-6 viral antigen in virus/EAE marmosets was markedly elevated and concentrated in brain lesions, similar to previously reported localizations of HHV-6 in MS brain lesions. Collectively, we demonstrate that asymptomatic intranasal viral acquisition accelerates subsequent neuroinflammation in a nonhuman primate model of MS.
National Acad Sciences