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

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 associat...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 115; no. 44; pp. 11292 - 11297
Main Authors Leibovitch, Emily C., Caruso, Breanna, Ha, Seung Kwon, Schindler, Matthew K., Lee, Nathanael J., Luciano, Nicholas J., Billioux, Bridgette J., Guy, Joseph R., Yen, Cecil, Sati, Pascal, Silva, Afonso C., Reich, Daniel S., Jacobson, Steven
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 30.10.2018
Subjects
Animals
Biological Sciences
Brain
Brain - virology
Callithrix
CD8 antigen
Children
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental - virology
Experimental allergic encephalomyelitis
Female
Herpes viruses
Herpesvirus 6, Human - pathogenicity
Inflammation
Inflammation - virology
Lesions
Male
Multiple sclerosis
Multiple Sclerosis - virology
Pathogens
Primates
Primates - virology
Roseolovirus Infections - virology
Viral infections
Viruses
human herpesvirus 6
EAE
marmoset
multiple sclerosis
viral trigger
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Summary: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.
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Edited by Michael B. A. Oldstone, The Scripps Research Institute, La Jolla, CA, and approved September 4, 2018 (received for review July 20, 2018)
Author contributions: E.C.L. and S.J. designed research; E.C.L., B.C., S.K.H., N. J. Lee, N. J. Luciano, B.J.B., J.R.G., C.Y., and P.S. performed research; J.R.G., P.S., and A.C.S. contributed new reagents/analytic tools; E.C.L., S.K.H., M.K.S., N. J. Lee, P.S., D.S.R., and S.J. analyzed data; and E.C.L. and S.J. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1811974115