AIDS as immune system activation: a model for pathogenesis.
Epidemiological evidence has implicated the human immunodeficiency virus (HIV) as the etiological agent of the acquired immunodeficiency syndrome (AIDS) (Barré-Sinoussi et al., 1983; Sarngadharan et al., 1984; Kitchen et al., 1984; Levy et al., 1984). Primary infection with HIV is accompanied by an acute flu-like illness followed by a relatively long period of asymptomatic infection, the delayed appearance of lymphadenopathy and a progressive decline in immune responsiveness. Eventually, significant reduction in T4 cell number occurs along with susceptibility to a variety of opportunistic infections. It is generally accepted that this lymphotropic retrovirus causes the depletion of the helper class of T lymphocytes (T4) by direct cytopathic effects and/or the induction of autoimmune killing of T cells (Fauci, 1987). Few objections have been raised to this model despite abundant experimental evidence that viraemia and the number of infected T cells are limited and constant throughout disease progression (Levy et al., 1985; Shaw et al., 1984; Harper et al., 1986; Duesberg, 1987). We believe that the current model for HIV-induced pathology is unsatisfactory. A hypothesis is advanced in which progressive immunodeficiency is caused by indirect mechanisms without widespread T cell infection, direct virus-mediated cytopathic effects, or autoimmunity. We propose that the latency of AIDS is not due to delayed viral expression and growth but rather to the accumulation of insults to an immune system with abnormal regulatory mechanisms induced by HIV infection of macrophages.
Ascher
M S
MS
Viral and Rickettsial Disease Laboratory, California Department of Health Services, Berkeley 94704.
Sheppard
H W
HW
D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D006678:HIV / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008954:Models, Biological; D013601:T-Lymphocytes / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
D014765:Viral Vaccines