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

Significance

Inflammatory processes drive the autoimmune disease multiple sclerosis (MS).

However, what triggers this inflammation re- mains 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. Be- cause 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.

Abstract

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 non- human 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

http://www.pnas.org/content/early/2018/10/09/1811974115?etoc=