Retroviruses and inflammatory myopathies in humans and primates.
The human immunodeficiency virus (HIV), the human T cell lymphotropic virus (HTLV-1), the human foamy retrovirus and the simian immunodeficiency viruses have been associated with the development of an inflammatory myopathy in humans and primates. The myopathy caused by HIV and HTLV-1 is not due to direct infection of the muscle by these viruses, but rather due to an immunopathologic process triggered by the viruses, mediated by autoaggressive CD8+ cells in the context of MHC-class I antigen expression. This has been based on a series of studies utilizing immunocytochemistry, in situ hybridization, polymerase chain reaction, and co-cultivation of human myotubes with the viruses or with HIV-1 and HTLV-1-infected homologous lymphoid cells. Because the clinical, histological and immunological picture of patients with retroviral-associated inflammatory myopathies is identical to that of patients with retroviral-negative inflammatory myopathy, there is a reasonable possibility that retroviruses may be candidate viruses in triggering inflammatory myopathies. In recent years, the antiretroviral drug AZT (Zidovudine), commonly used for the treatment of AIDS, has been shown to cause a distinct mitochondrial myopathy characterized by depletion of the muscle mitochondrial DNA due to AZT's ability to inhibit the gamma-DNA polymerase of the mitochondrial matrix. Distinction of the AZT-myopathy is clinically important because it responds to discontinuation of AZT and to administration of another antiretroviral agent such as ddI or ddC.
Dalakas
M C
MC
Neuromuscular Diseases Section, National Institutes of Health, Bethesda, Maryland 20892.
D015658:HIV Infections / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D015490:HTLV-I Infections / Q000382:microbiology / Q000473:pathology; D006801:Humans; D009220:Myositis / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D012190:Retroviridae; D012192:Retroviridae Infections / Q000188:drug therapy / Q000473:pathology; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
D015215:Zidovudine