Association of a Novel Retrovirus in Multiple Sclerosis?
ABSTRACT & COMMENTARY
Source: Perron H, et al. Molecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis. Proc Nat Acad Sci 1997;97:7583-7588.
Perron et al have published their latest report further identifying a novel retrovirus isolated from leptomeningeal, choroid plexus, and transformed B-cell lines from MS patients. Extracellular viral particles were characterized using reverse transcriptase-PCR (RT-PCR) methods. The viral RNA sequences could be detected in five out of 10 samples of MS cerebrospinal fluid but in none of the 10 control patients with other neurological disease. In four out of the five MS patients negative for the retrovirus, the patients had received previous immunosuppressive treatment with corticosteroids or cyclophosphamide.
The MS-associated retrovirus (MSRV) sequences showed a 75% homology to a previously described human endogenous retroviral sequence (ERV9). Many retroviral sequences have integrated into the human host DNA over millions of years of evolution and now comprise up to 5% of the mammalian genome. The investigators were unable to exclude the possibility that the MSRV was truly an exogenous retrovirus vs. an endogenous retrovirus producing extracellular virions.
COMMENTARY
Despite recent therapeutic advances in MS through the empiric application of interferons, the primary cause(s) and pathogenesis of this inflammatory demyelinating disease remain obscure. Perron et al have presented a preliminary case for a novel retroviral sequence that can be associated with MS. Certainly there is precedent for several characterized mammalian retroviruses that cause a variety of neurological and oncological disease (e.g., HTLV-I associated myelopathy in humans).
These findings will require independent confirmation by other labs with a larger blinded series of MS patients and controls before a more specific association can be made. Previous reports implicating human herpes viruses having a role in MS (Neuro Alert 1996;14:51-52) may also be relevant, as Perron et al note that herpes gene regulatory proteins may play an important role in MSRV activation. If MSRV is determined to be an etiologic factor in MS, an understanding of the primary disease pathology may be at hand. In addition to interferon, which has general antiviral properties, specific antiviral strategies against MSRV, both pharmacologic and gene therapies, can then be tested to potentially control the course of MS much more so than in current clinical practice. ba
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