Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults aged 20 to 40 years, with an estimated 350,000 to 500,000 patients in the United States. The disease is characterized by demyelinating lesions in the brain and spinal cord. The etiology of MS has not been defined, but clearly the lesions represent the final result of an immunopathologic process. One hypothesis proposed to explain the pathogenesis in MS is that a viral infection induces demyelination by eliciting either a direct or indirect immune response within the central nervous system (CNS). Although studies on virus induced demyelination in animals and humans support this hypothesis, attempts to consistently detect infectious virus in MS tissue have failed. However, our preliminary data demonstrate that coronavirus RNA and antigen are detectable in MS brain and that coronaviruses can actively infect the CNS of primates resulting in demyelination. Although the disease spectrum of coronaviruses in other non-primate species is diverse, including elegant models of CNS demyelination and immune system interactions, presently identified roles for coronaviruses in human disease remain limited to upper respiratory infections and enteritis. Our data now suggest that coronaviruses may play a role in induction and/or maintenance of demyelination in MS. The goal of this proposal is to clone coronavirus RNA directly from MS tissue and then to sequence these clones. Classification of these coronaviruses relative to other coronaviruses, based on the sequence of defined viral genes, will be a critical first step in designing future studies on the possible mechanism(s) of coronavirus CNS pathogenesis in humans. In addition, identification of the specific coronavirus(es) that has potential to infect human brain will possibly help in designing diagnostic, prevention and treatment of strategies for MS.
| Murray, R S; Cai, G Y; Soike, K F et al. (1997) Further observations on coronavirus infection of primate CNS. J Neurovirol 3:71-5 |
