Human retroviruses and demyelinating diseases.
The consequences of human retroviral infections have had an unprecedented impact on the medical, scientific, and social institutions of the last two decades of this century. The nervous system as an end target organ figures prominently in the constellation of diseases associated with HTLV and HIV infection and numerous syndrome complexes have been recognized that reflect dysfunction of the brain, spinal cord, nerve roots, peripheral nerves, or muscle. HAM/TSP, associated with HTLV-I and rarely with HTLV-II infections, and encephalomyelitis, associated with HIV infection, may present with clinical, laboratory, neuroelectrophysiologic, and neuroimaging features closely resembling MS. A careful systematic search for associated disease processes and review of the medical history, however should raise the suspicion of possible retroviral infection. In the appropriate setting, because of the pleiotropy in disease expression and the high prevalence of retroviral infection in many areas of the United States, clinicians should have a low threshold for ordering diagnostic testing for HIV and HTLV when considering a retroviral cause for a neurologic disorder. The retroviruses are pervasive throughout the vertebrate subphylum and share common elements within their genome that encode for promoters and structural proteins and are distinguished from each other by sets of transactivating and regulating genes. The latter group of genes serve to regulate viral replication by the induction and post-transcriptional and post-translational modification of retrovirally encoded gene products. In addition, the transactivating gene products can activate and upregulate the expression of a variety of host cellular genes, many of which possess immune-related functions. The viral particle or specific components of certain viral structural proteins may be directly toxic to neural tissues. Also, during the replicative phase, retroviruses are recognized by host defense mechanisms, which mount considerable cellular and humoral immune responses. The spectrum of retroviral-associated neurologic diseases therefore may represent a complex interaction among viral antigen-induced immunity, the production of neurotoxic viral peptides, and the abnormal induction and expression of cellular genes with potent bioactivity.
Greenberg
S J
SJ
Department of Neurology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
D015658:HIV Infections / Q000150:complications; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000150:complications; D009103:Multiple Sclerosis / Q000209:etiology*; D009422:Nervous System Diseases / Q000209:etiology*; D012192:Retroviridae Infections / Q000150:complications*