Herpesvirus trigger accelerates neuroinflammation in a nonhuman primate model of multiple sclerosis
| Autor: | Afonso C. Silva, Breanna Caruso, Nathanael J. Lee, Bridgette Jeanne Billioux, Steven Jacobson, Nicholas J. Luciano, Matthew K. Schindler, Daniel S. Reich, Emily C. Leibovitch, Seung Kwon Ha, Cecil Chern-Chyi Yen, Pascal Sati, Joseph R Guy |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Primates Encephalomyelitis Autoimmune Experimental Multiple Sclerosis Letter viruses Herpesvirus 6 Human Roseolovirus Infections Virus Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Immunology and Inflammation biology.animal medicine Animals Neuroinflammation Inflammation marmoset Multidisciplinary biology business.industry EAE Multiple sclerosis Experimental autoimmune encephalomyelitis Marmoset virus diseases Brain Callithrix Biological Sciences medicine.disease biology.organism_classification Disease Models Animal 030104 developmental biology Immunology Human herpesvirus 6 human herpesvirus 6 Female viral trigger business 030217 neurology & neurosurgery CD8 |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 |
| Popis: | Significance Inflammatory processes drive the autoimmune disease multiple sclerosis (MS). However, what triggers this inflammation remains unknown. Several herpesviruses (HHVs), such as HHV-6 typically acquired during childhood, are associated with MS. The temporal separation between HHV-6 acquisition and MS development complicates its study as a disease trigger. Because rodents are not susceptible to HHV-6 infection, we utilized nonhuman primates to examine the impact of HHV-6 infection on an experimental MS-like disease. The viral infections were asymptomatic; however, the MS-like disease was significantly accelerated in all virally inoculated animals. Our data support the hypothesis that viruses may act as triggers to lower the threshold for autoimmunity, and warrant trials of antiviral interventions in early disease stages. 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. |
| Databáze: | OpenAIRE |
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