HIV-1-INDUCED NEUROPATHY: HIV NEF EXHIBITS STRUCTURAL AND FUNCTIONAL SIMILARITIES TO PEPTIDES TARGETED TO ION CHANNELS (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

HIV-1-INDUCED NEUROPATHY: HIV NEF EXHIBITS STRUCTURAL AND FUNCTIONAL SIMILARITIES TO PEPTIDES TARGETED TO ION CHANNELS (MEETING ABSTRACT)

Fifteenth Symposium of the International Association for Comparative Research on Leukemia and Related Diseases. October 6-11, 1991, Padova/Venice, Italy, p. 103, 1991.. Unique Identifier : AIDSLINE ICDB/92682441
Werner T; Ferroni S; Saermark T; Brack-Werner R; Banati RB; Mager R; Steinaa L; Keutzberg G; Erfle V; GSF-Center for Environmental and Health Res., Munchen, Germany

Abstract: The molecular pathways leading to the HIV-mediated neuropathies are not well understood. Possibilities such as the neuronal killing of gp120 (Brenneman et al, 1990), the secretion of neurotoxic substances by HIV-1-infected macrophages (Giulian et al, 1990) or the neurotoxic activity of HIV-1 tat (Sabatia et al, 1991) imply an active replication of HIV and a destruction of cells in the infected nervous system. Virological and histopathological data do not support this view. In contrast, the overall picture of CNS infection by HIV-1 points more to a functional interference by HIV. In vitro studies with brain cells indicate that replication of HIV-1 is low and without obvious cytotoxic effects. We have demonstrated that the latent infection of brain cells (astrocytes, glial cells) is characterized by expression of the nef protein. Computer analysis of the possible structure of the nef proteins of HIV-1, HIV-2 and SIV has revealed striking structural homologies to peptides targeted to K and Na channels as found in scorpions. This similarity is predominantly in the conserved position of charged amino acids which induce a certain loop structure. The computer prediction could be substantiated by data from the crystal structure of one of the scorpion peptides. Patch-clamp experiments in chicken dorsal root ganglia measuring K channels also demonstrated the functional similarity of HIV-1 nef to these peptides. Thus, the mechanism of HIV neuropathies may be mediated by functional interference of nerve cell conductivity without viral replication and obvious cell destruction in the CNS.

Keywords: Animal Astrocytes Chickens Gene Products, nef/*GENETICS Gene Products, tat Human HIV Envelope Protein gp120 HIV Infections/COMPLICATIONS/*GENETICS/PATHOLOGY HIV-1/*GENETICS/PHYSIOLOGY HIV-2/GENETICS Macrophages/METABOLISM Nervous System Diseases/ETIOLOGY/*GENETICS/PATHOLOGY Neuroglia Potassium Channels Sodium Channels Spinal Nerve Roots SIV/GENETICS Virus Replication ABSTRACT
920830
M9281097

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