# Diverse Functions of HIV-1 Capsid During Postentry Events

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $449,461

## Abstract

Project Summary
The HIV-1 capsid, which encloses viral and host components essential for establishing infection, influences
every post-entry step, including reverse transcription, nuclear entry and integration targeting. These capsid-
mediated events are governed by HIV-1 uncoating, a process in which the conical core sheds viral capsid
proteins (CA) and transforms into reverse transcription complexes and then pre-integration complexes.
Uncoating of the viral capsid is regulated by both core stability and capsid-binding host cofactors. Much
remains to be learned about how the uncoating process is coordinated to facilitate viral propagation. Temporal
deviations from the normal course of capsid disassembly (delayed or accelerated uncoating) by antiviral
factors or pharmacological manipulation can severely impair viral infectivity. However, it still remains unclear
precisely how intrinsic core stability affects capsid disassembly and downstream events. Our preliminary
studies have identified a natural HIV-1 strain that appears to alter core stability without compromising viral
fitness. In Aim 1, we will characterize a broad range of biological properties of this unique variant and also
exploit core-destabilizing activity of capsid-targeting antivirals as a tool to study capsid stability. Current models
posit that core disassembly impacts innate sensing of HIV-1 DNA but mechanistic details have yet to be
elucidated. In Aim 2, we propose to examine how perturbation of uncoating by manipulating core stability and
capsid interactions with host proteins affects innate immune responses. Capsid uncoating also plays roles in
nuclear events, such as nuclear import and integration targeting. In Aim 3, we will address how these events
are functionally linked and contribute to optimal viral growth by using various experimental approaches,
including novel high-throughput single-cell assays.

## Key facts

- **NIH application ID:** 9979730
- **Project number:** 5R01AI100720-10
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Masahiro Yamashita
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $449,461
- **Award type:** 5
- **Project period:** 2012-04-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979730

## Citation

> US National Institutes of Health, RePORTER application 9979730, Diverse Functions of HIV-1 Capsid During Postentry Events (5R01AI100720-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9979730. Licensed CC0.

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