FUNCTIONAL EVOLUTION OF SIV VARIANT VIRUSES

  • Poss, Mary (PI)

Project: Research project

Project Details

Description

Genetic variation in the envelope gene and slow onset of clinical disease
characterize lentivirus infections. Variants isolated late in infection
are generally cytopathic in vitro and, in animal experiments, more
pathogenic in vivo than the parent virus. Many defects in immune cell
function are evident, however, during asymptomatic periods and may be
essential factors in overall disease progression. At these early time
points post-infection, virus is sequestered and replicating in lymph nodes
but not in peripheral blood lymphocytes. Lymph nodes may, therefore,
harbor a population of variant viruses functionally significant to viral
pathogenesis. In this proposal, variants from lymph nodes and peripheral
blood lymphocytes of preclinical SIVMne infected macaques will be analyzed
and the functional properties conferred on gp120 by env mutations of these
variants determined. Identification of early variant viruses with
specific functional capabilities will be valuable in designing therapeutic
intervention for early seroconverters. The specific aims are as follows:

AIM 1: To determine the temporal relationship between SIV variants
arising in lymph node to those found in PBMC of macaques infected
with a molecular clone of SIVMne.
DNA from lymph node and peripheral blood lymphocytes of SIV-
infected macaques will be analyzed by PCR cloning of env.

AIM 2: To construct chimeric viruses containing representative early
variant gp120.
Variant env sequences that are specific to lymph node or
peripheral blood lymphocytes or that arise early in infection will
be used to construct variant env-SIVMne chimeras.

AIM 3: To determine the effect of env mutations on functional activity of
gp120.
Env-specific chimeras will be evaluated for the functional
properties of receptor binding, cell activation and cell protein
co-localization.
StatusFinished
Effective start/end date9/30/948/31/95

Funding

  • National Institute of Allergy and Infectious Diseases

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