# Intravacuolar network dense granule protein biology in chronic Toxoplasma infection

> **NIH NIH R21** · DARTMOUTH COLLEGE · 2021 · $246,000

## Abstract

Chronic infection with Toxoplasma gondii will often reactivate and cause life-threatening Toxoplasmic
encephalitis in patients with AIDS or other immune deficiencies. The molecular basis of chronic infection with
Toxoplasma gondii is the tissue cyst that develops and persists in the central nervous system. The elimination
of cysts in infected individuals would prevent Toxoplasmic encephalitis, as well as deteriorating neurocognitive
function that occurs in HIV-positive individuals even prior to AIDS. However, no drug or other therapy exists
that can target the chronic Toxoplasma cyst. Currently, there is a deficit in fundamental biological knowledge
regarding parasite and host biology that controls the development, maintenance, and reactivation of
Toxoplasma cysts. We hypothesize that dense granule (GRA) proteins that associate with the intravacuolar
network (IVN) membrane system play biological roles in manipulating the host CD8+ T cell responses that
control chronic infection, as well as biological roles as structural, signaling, or sensing components of a
membrane system that influences the development of cysts, the maintenance of cysts, and the reactivation of
cysts. This hypothesis for a dual role for IVN associated GRA proteins in chronic infection is supported by our
preliminary data. This exploratory R21 proposal will investigate the role of IVN GRAs in cyst development,
maintenance and reactivation (Aim 1), and in manipulating the host CD8+ T cell responses that determine
whether cysts are maintained, cleared, or reactivated (Aim 2). We anticipate these high impact studies will
expand our fundamental knowledge of the biology that regulates cyst development, maintenance, and
reactivation, and may therefore establish a molecular basis for an intervention that can eradicate chronic
Toxoplasma gondii infection.

## Key facts

- **NIH application ID:** 10084815
- **Project number:** 5R21AI152687-02
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** DAVID J BZIK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $246,000
- **Award type:** 5
- **Project period:** 2020-01-13 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084815

## Citation

> US National Institutes of Health, RePORTER application 10084815, Intravacuolar network dense granule protein biology in chronic Toxoplasma infection (5R21AI152687-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10084815. Licensed CC0.

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