Herpes virus induces demyelination in rats

[frodo]

Nothing to do with EAE

Herpes Simplex Virus 1 induces brain inflammation and multifocal demyelination in cotton rats Sigmodon hispidus

https://jvi.asm.org/content/early/2019/ ... 9.abstract

ABSTRACT

Demyelinating CNS disorders like multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) have been difficult to study and treat due to the lack of understanding of their etiology. Numerous cases point to the link between HSV infection and multifocal CNS demyelination in humans, however, convincing evidence from animal models has been missing. In this work we found that HSV-1 infection of cotton rats Sigmodon hispidus via a common route (lip abrasion) can cause multifocal CNS demyelination and inflammation. Remyelination occurred shortly after demyelination in HSV-1-infected cotton rats, but could be incomplete, resulting in “scars”, further supporting an association between HSV-1 infection and multifocal demyelinating disorders. Virus was detected sequentially in the lip, trigeminal ganglia, and the brain of infected animals. Brain pathology developed primarily on the ipsilateral side of the brainstem, in the cerebellum, and contralateral side of the forebrain/midbrain, suggesting that the changes may ascend along the trigeminal lemniscus pathway. Neurologic defects occasionally detected in infected animals (e.g., defective whisker touch and blink responses, compromised balance) could be representative of the brainstem/cerebellum dysfunction. Immunization of cotton rats with a split HSV-1 vaccine protected animals against viral replication and brain pathology, suggesting that vaccination against HSV-1 may protect against demyelinating disorders.

IMPORTANCE

Our work demonstrates for the first time a direct association between infection with herpes simplex virus 1, a ubiquitous human pathogen generally associated with facial cold sores, and multifocal brain demyelination in an otherwise normal host, cotton rat Sigmodon hispidus. For a long time demyelinating diseases were considered to be autoimmune in nature and were studied by indirect methods, such as immunizing animals with myelin components or feeding them toxic substances that induce demyelination. Treatment against demyelinating diseases has been elusive, partially because of their unknown etiology. This work provides the first experimental evidence for the role of HSV-1 as the etiologic agent of multifocal brain demyelination in a normal host and suggests that vaccination against HSV-1 can help to combat demyelinating disorders.