ROLES(S) OF GLYCOSPHINGOLIPIDS IN NEURAL AIDS

Project: Research project

Project Details

Description

Description (Adapted from Applicant's abstract): Glycospingolipids (GSLs) have
been implicated as fusion co-factors for human immunodeficiency virus (HIV) the
causative agent of AIDS. The overall goal of the proposed research is to
determine the role(s) of GSLs in the interaction of HIV-1-associated gp120 with
different cell types of the central nervous system (CNS) or models thereof, and
to use that information to develop possible inhibitors of that interaction.
Emphasis is placed on CNS cells or possible models thereof because many
individuals infected with HIV-1 eventually develop HIV-1-associated dementia
(HAD) in the absence of opportunistic infection. The specific aims of this
proposal are to: 1) identify which GSL(s) is/are the ligand(s) for
HIV-1-associated gp120. Experiments will be done to confirm that GSLs are
necessary for HIV-1 entry and, in those instances where they are necessary, the
GSLs adhered to by HIV-1 will be identified. 2) determine the contribution of
the GSL saccharide and ceramide moieties to interactions with HIV-1-associated
gp120. Experiments will be carried out to determine whether the saccharide
portion of each GSL adhered to by HIV-1 can inhibit HIV-1 adherence to the GSL
immobilized on plastic or whether a "multivalent" saccharide or the ceramide
portion per se is needed. 3) determine whether the inhibitor of HIV-1
associated gp120-mediated adherence to a GSL is able to inhibit gp120-mediated
entry of the virus into cells expressing the GSL. The effectiveness of the
inhibitor identified in the 2nd aim at blocking infection will be monitored
using microglia and asrtrocytes. The effectiveness of the virus at inducing
apoptosis in neuroblastoma cells in the presence and absence of inhibitor will
also be ascertained. The results should indicate the portion of the GSL(s)
recognized by HIV-1. They may also provide the basis for development of an
inhibitor able to block adherence of HIV-1 to its GSL fusion co-factor thereby
blocking its entry into the cell.
StatusFinished
Effective start/end date4/1/003/31/01

Funding

  • National Institute of Neurological Disorders and Stroke: $226,611.00

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