# Characterization of full-lengh CPSF6 and its interaction with HIV capsid

> **NIH NIH F31** · YALE UNIVERSITY · 2024 · $33,950

## Abstract

PROPOSAL SUMMARY / ABSTRACT:
HIV is a retrovirus that achieves infection through integration of its viral DNA into the host genome of non-
dividing cells. To execute this function, HIV must ensure the nuclear import of its reverse-transcribed genetic
material, which is protected inside of a proteinaceous fullerene cone known as the capsid. As the dimensions
of the capsid are larger than the conventionally accepted width of the nuclear-pore-complex (NPC), it was long
thought that disassembly of the capsid in the host cytoplasm was essential for HIV’s genomic material to gain
access to the nucleus. Recent work has demonstrated that the central channel of the NPC is highly dynamic
and able to accommodate an intact HIV capsid; subsequently several groups have directly observed
assembled capsids within the nuclear compartment. Work from the last decade suggests that the cellular
protein CPSF6 (Cleavage and Polyadenylation Specificity Factor 6) governs the nuclear import of viral
genomic material through interactions with the HIV capsid. The work outlined in this proposal, broken into
three independent aims, seeks to provide biochemical and structural understanding of this interaction. In AIM1,
I will use real-time binding techniques to provide insight into the biophysical principles of the CPSF6-capsid
interactions. I hypothesize that CPSF6 has a previously unappreciated binding site at the tri-hexamer interface
of the HIV capsid. In AIM2, I will employ our library of capsid assemblies to determine the structure of CPSF6
bound to the capsid protein and confirm these structural features with functional assays. Finally, in AIM3, I will
employ a DNA origami mimic of the NPC in an in vitro reconstitution dissect CPSF6’s contribution to nuclear
import of the HIV capsid. I hypothesize that CPSF6 can compete with Nup153 and thereby release the capsid
from the nuclear basket.

## Key facts

- **NIH application ID:** 10839022
- **Project number:** 1F31AI181652-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Christian Joseph Freniere
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $33,950
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839022

## Citation

> US National Institutes of Health, RePORTER application 10839022, Characterization of full-lengh CPSF6 and its interaction with HIV capsid (1F31AI181652-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10839022. Licensed CC0.

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