# HOST-VIRUS INTERACTIONS IN HIV-INDUCED SICCA SYNDROME

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 1993 · $365,202

## Abstract

In the current grant period while studying Reiter's syndrome in HIV+
patients we encountered an entity often presenting as a rheumatic disease
associated with a sicca syndrome that was designated diffuse infiltrative
lymphocytosis syndrome, or DILS. The accumulated findings led to the view
that genetic differences in the host immune recognition structures
influence the course and outcome of HIV infection in those developing DILS
towards a diminished tendency to develop impaired CD4 T-cell function and
opportunistic infections through a massive lymphocytic response of CD8 T-
cells and lesser proportions of CD4 T-cells. This response also appears to
mediate the pathogenesis of the rheumatic disorder.  These T-cell are
characterized by a restriction in their alpha-betaTCR expression
suggesting that there is an underlying common antigen recognition event in
DILS. Because of the importance of the consequences of these recognition
events to the general question of HIV infection, and particularly because
DILS is a model for understanding the pathogenesis of idiopathic Sjogren's
syndrome, the decision was made to focus this proposal on gaining a better
understanding of the fundamental mechanisms underlying DILS. The specific
aims include: development of an improved understanding of the natural
history of adult and pediatric DILS.  Characterization of HIV strain
diversity in DILS at the functional and structural level. Obtaining an
explanation for the preponderant localization of HIV in monocytes and why
the evolution to T-tropic strains occurs at low frequency and then very
late in the course of HIV infection in DILS.  Delineation of genetic
determinants of susceptibility to the development of DILS with emphasis on
understanding the physico-chemical basis of the positive association with
two structurally related MHC class II alleles, DRB1 *1102 and DRB1 *1301,
and the conformationally determined pattern of strong positive and
negative association with several class I alleles. Exploring the
significance of the striking mimetic homology between the 3rd diversity
region of the class II susceptibility alleles and a segment of the HIV-1
V3 loop involved in determining M-tropism that suggests individuals with
DILS exhibit either tolerance of M-tropic strains, or more likely enhanced
autologous reactivity against these strains through molecular mimicry
which prevents evolution of HlV-1 to functional T-tropic strains.
Initiation of a comprehensive analysis of the nature of the responding T-
cell population and search for the antigenic determinant(s) driving this
response using the over-utilized alpha-beta TCR elements as markers with
the objective of understanding its significance in the outcome of the
host-virus interactions.

## Key facts

- **NIH application ID:** 3159812
- **Project number:** 2R01AR039626-06
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **SAM.gov UEI:** F4N1QNPB95M4
- **Principal Investigator:** Robert J Winchester
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $365,202
- **Award type:** 2
- **Project period:** 1991-09-30 → 1998-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159812

## Citation

> US National Institutes of Health, RePORTER application 3159812, HOST-VIRUS INTERACTIONS IN HIV-INDUCED SICCA SYNDROME (2R01AR039626-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159812. Licensed CC0.

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