IMMUNOLOGICAL NO SYNTHASE - ELEVATION IN SEVERE AIDS DEMENTIA AND INDUCTION BY HIV-1 GP41

Indirect mechanisms are implicated in the pathogenesis of the dementia associated with human immunodeficiency virus-typo 1 (HIV-1) infection . Proinflammatory molecules such as tumor necrosis factor alpha and ei cosanoids are elevated in the central nervous system of patients with HIV-1-related dementia. Nitric oxide (NO) is a potential mediator of n euronal injury, because cytokines may activate the immunologic (type I I) isoform of No synthase (iNOS). The levels of iNOS in severe HIV-1-a ssociated dementia coincided with increased expression of the HIV-1 co at protein gp41. Furthermore, gp41 induced iNOS in primary cultures of mixed rat neuronal and glial cells and killed neurons through a NO-de pendent mechanism. Thus, gp41-induced NO formation may contribute to t he severe cognitive dysfunction associated with HIV-1 infection.