AIDS and its dementia as a neuropeptide disorder: role of VIP receptor blockade by human immunodeficiency virus envelope.

The CD4 molecule was originally described as a marker for a subset of lymphocytes; however, recent work has shown that a similar, if not identical, molecule is present on human brain. We have realized that this cell-surface recognition molecule is normally modulated by vasoactive intestinal peptide (VIP), one of the 50 or more neuropeptides that compose a shared intercellular network joining the brain, glands, and immune system. Human immunodeficiency virus (HIV), the etiological agent of acquired immunodeficiency syndrome (AIDS), has been found to mimic VIP binding via peptide T (4-8), a pentapeptide sequence present in approximately the same region of all 20 HIV isolates whose sequences are currently known. AIDS dementia results from interference of gp120, present on the HIV envelope protein, with normal VIP-ergic neurotrophic effects, and effects on cerebral blood flow.