# Single-cell analysis of HIV-1 production and transmission

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $521,970

## Abstract

Project Summary
Single-cell technologies have begun to reveal novel aspects of HIV-1 replication. However, it remains unclear
how cellular heterogeneity influences transmissibility of virus-infected cells. We have developed quantitative
single-cell assays for HIV-1 production and transmission. Our preliminary studies showed substantial cell-to-
cell variations in both virus yield and transmissibility. Such diverse phenotypic outcomes of infection were
unexpected and may offer new paradigms for HIV-1 biology. The major goal of this proposal is to gain
quantitative and mechanistic insights into single-cell heterogeneity in HIV-1 production and transmission. In
addition, a simple and rapid method for single-cell detection of virus-producing cells will be harnessed to
develop novel assays for studying viral latency. In specific aim 1, we will study how virally induced diversity and
cell-intrinsic heterogeneity contribute to cellular differences in productivity and infectiousness of individual
virus-infected cells. A barcoded viral library will be utilized for high-throughput tracking of single-cell infection
events in vitro and in an ex vivo tissue explant model. In specific aim 2, we will investigate how virus-infected
cells shut off virion production during latency establishment to learn temporal changes in the cell fate during
latency establishment. Single-cell detection of virion production will be used for quantification of the size of
latent reservoirs and efficacy evaluation of latency reversal reagents. In specific aim 3, we will analyze single-
cell transcriptome profiles to elucidate the biological basis for cell-to-cell heterogeneity of virus-infected cells by
combining quantitative single-cell assays for virus production and transmission with single-cell RNA
sequencing.

## Key facts

- **NIH application ID:** 10132234
- **Project number:** 5R01AI145570-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Masahiro Yamashita
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $521,970
- **Award type:** 5
- **Project period:** 2019-04-04 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132234

## Citation

> US National Institutes of Health, RePORTER application 10132234, Single-cell analysis of HIV-1 production and transmission (5R01AI145570-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10132234. Licensed CC0.

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