Human endogenous retroviruses in the aetiology of MS.

ABSTRACT

Several lines of investigation have provided strong indications for an association between the immune-mediated, neurologic disease multiple sclerosis (MS) and human endogenous retroviruses (HERVs). Whether the relationship is causal is yet to be established. Endogenous retroviruses are pathogenic-in other species than the human. Several aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been documented, both for cells in the periphery and in the central nervous system. Specific HERV-encoded genes and certain gene products (envelope proteins, Envs) appear strongly associated with the disease and have pathogenic potential. Most HERV sequences are non-functional, whereas some HERV loci have coding potential but remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, de-repression, and also involvement of retroviral restriction factors, is emerging. Disease intervention by means of antiretrovirals has potential as a novel therapeutic strategy in MS treatment; this is compounded by the apparently reduced risk of MS in HIV infection as a consequence of therapy. Extensive studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are needed.