# Elucidating the structural adaptation of HIV-1 capsids during critical host-factor interactions

> **NIH AI F31** · FLORIDA STATE UNIVERSITY · 2026 · $42,065

## Abstract

PROJECT SUMMARY
The HIV-1 capsid provides a protective conical enclosure for the transport of the viral genome to its integration
sites inside the nucleus. The capsid must uncoat to release the newly formed vDNA and to establish a permanent
infection of target cells. When? where? and how? capsids are uncoated remain unclear and hotly debated in the
field. This is especially relevant, as new highly active antiretrovirals such as the clinically approved drug
Lenacapavir are being developed to combat virus infection. For infection to proceed, the core must cross the
nuclear pore complex (NPC) to deliver the viral DNA (vDNA) to integration sites in the nucleus. This process
requires structural remodeling of the capsid, which adapts through elastic deformation to penetrate the NPC’s
~64 nm channel. However, the mechanisms underlying capsid remodeling remain poorly understood. My
preliminary evidence suggests that the phase separation properties of the host factor CPSF6 stabilize capsid
structures in vitro and facilitates capsid trafficking in the nucleus of living cells to nuclear speckles, which are
actively transcribing chromatin compartments favored for HIV-1 integration. Disruption of these processes,
including with capsid-targeting drugs, impairs nuclear entry and viral infectivity, highlighting their biological
relevance. This proposal has two specific aims. AIM-1 will resolve how CPSF6 influences HIV-1 capsid
morphology in vitro. Using affinity captured virus particles, correlative light and electron microscopy (CLEM), and
cryo-electron tomography (cryo-ET), I will reconstruct CPSF6-bound capsid structure and test the morphological
adaptations of the HIV-1 core by host-factor interactions. AIM-2 will extend these findings to infected cells. I will
use live-cell imaging, and a CLEM-guided cryo-focused ion beam milling (FIB) of cells and cryo-ET of a lamella
prepared at the location of HIV-1 cores to capture capsid structures at multiple stages of entry, from the
cy

## Key facts

- **NIH application ID:** 11328424
- **Project number:** 1F31AI197983-01
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Jonathan Rene Andino Moncada
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $42,065
- **Award type:** 1
- **Project period:** 2026-05-01T00:00:00 → 2029-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11328424

## Citation

> US National Institutes of Health, RePORTER application 11328424, Elucidating the structural adaptation of HIV-1 capsids during critical host-factor interactions (1F31AI197983-01). Retrieved via AI Analytics 2026-06-30 from https://api.ai-analytics.org/grant/nih/11328424. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*