# Project 2 - Identification of the source of viral rebound using SIV proviral genome analysis

> **NIH NIH P01** · JOHNS HOPKINS UNIVERSITY · 2021 · $337,770

## Abstract

Abstract
 The key to developing successful strategies to delay and ultimately prevent viral rebound
upon treatment interruption is to identify the source and mechanisms of viral rebound. Ongoing
debates regarding the source of rebound include 1) whether CD4+ T cells or tissue macrophages
are the dominant source of rebound, 2) whether ongoing cycles of replication in the lymphoid
tissue contribute to rebound, 3) whether HIV-1 infection may actively drive the clonal expansion
of infected cells through integration into proliferation-related genes. We propose here to explore
these issues in collaborative studies in the SIV model using a new technology developed by our
group. Using full length, single genome sequencing of HIV-1 proviruses, we have recently shown
that the vast majority (>95%) of HIV-1 proviruses in patient cells are defective. This discovery
greatly complicates analysis of issues such as the source of rebound viremia, the possibility of
ongoing viral evolution during treatment, and the role of clonal expansion in viral persistence. In
preliminary studies, we have shown that most SIV proviruses are also defective. By focusing on
those proviruses that are not defective, we will be able to better understand the cellular sources
of viral rebound and to address controversies regarding ongoing viral replication during treatment
and reservoir expansion through proliferation of infected cells. This studies will be carried out in
conjunction with Hopkins colleagues who will employ other novel assays for replication-competent
SIV in the cohorts of treated macaques described in the application. Together these studies
should provide new insights into the sources of viral rebound.

## Key facts

- **NIH application ID:** 10174709
- **Project number:** 5P01AI131306-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ROBERT F SILICIANO
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $337,770
- **Award type:** 5
- **Project period:** 2017-06-23 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174709

## Citation

> US National Institutes of Health, RePORTER application 10174709, Project 2 - Identification of the source of viral rebound using SIV proviral genome analysis (5P01AI131306-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10174709. Licensed CC0.

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