February 2000, Volume 6, Issue 1, Pages 51 - 60

Article

Expression of complement inhibitor protein CD59 in human neuronal and glial cell lines treated with HIV-1 gp41 peptides Young Hae Chong & Myung Ju Lee Department of Microbiology, College of Medicine, Division of Molecular Biology and Neuroscience, Medical Research Center, Ewha Womans University, 911-1, Mok-6-dong, Yangcheonku, Seoul, Korea, 158-056     Correspondence to: YH Chong, Department of Microbiology, College of Medicine, Division of Molecular Biology and Neuroscience, Medical Research Center, Ewha Womans University, 911-1, Mok-6-dong, Yangcheonku, Seoul, Korea, 158-056

Keywords

HIV-1 associated dementia;   gp41;   CD59;   protein kinase inhibitor;   proinflammatory cytokines;   antioxidants;   anti-inflammatory agents

Abstract

In attempts to elucidate the pathogenic mechanisms involved in neurodegeneration in AIDS patients with cognitive deficits, the possible effect of HIV-1 transmembrane envelope protein gp41 on expression of the membrane inhibitor of complement mediated cytolysis (CD59) was assessed in human neuronal (SK-N-SH) and astroglial (T98G) cell lines. Western blotting analyses demonstrated that an immunodominant (ID, aa 598 - 613) gp41 peptide as well as the recombinant gp41 protein encompassing this domain markedly reduced CD59 level in a dose dependent manner whereas p24 and control peptide had little effect. RT - PCR showed that ID peptide also elicited a reduction in the expressed CD59 mRNA level. This gp41 peptide apparently down-regulated phorbol 12,13-dibutyrate induced elevation of CD59 at the protein and mRNA levels in a manner similar to that conferred by protein kinase C inhibitor, H-7 or staurosporine in SK-N-SH. Interestingly, proinflammatory cytokines such as IL-1 or IFN- as well as LPS greatly decreased CD59 in SK-N-SH and to a lesser extent in T98G whereas TNF- did not significantly alter it. In contrast, antioxidants and anti-inflammatory agents enhanced CD59 expression reversing gp41 peptide mediated inhibitory effect in SK-N-SH. Our data suggest that high level of gp41 or its metabolites as well as impaired protein kinase response, chronic inflammation or antioxidant depletion within HIV-1 infected brains may be associated with a diminished expression of CD59 which would render neuronal cells to susceptible to indirect bystander lysis in the presence of autologous complement. Journal of NeuroVirology (2000) 6, 51 - 60.

Received 6 April 1999; Revised 27 August 1999; Accepted 9 September 1999

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