# APOBEC3 Proteins in HIV Restriction

> **NIH NIH R37** · UNIVERSITY OF MINNESOTA · 2021 · $458,762

## Abstract

The discovery of the antiviral APOBEC3 (A3) proteins is regarded as one of the most therapeutically
promising breakthroughs in HIV/AIDS molecular virology. Four different A3 proteins have the capacity
to restrict HIV replication by incorporating into assembling viral particles, physically interfering with the
progression of reverse transcription, and deaminating viral cDNA cytosines to uracils. The latter
antiviral activity is the defining hallmark of A3-mediated restriction, explaining the genomic strand G-
to-A mutations that are frequently observed in patient-derived viral sequences. In the next phase of
this ongoing project, we will focus on addressing two related questions, which are regarded as major
“black boxes” in the field. Namely, how are the HIV-1 restrictive A3s regulated post-translationally, and
how do these regulatory mechanisms effect the RNA-mediated process of encapsidation, which is an
essential step in the overall virus restriction mechanism? These questions will be answered by
combining comprehensive proteomics, genetics, and next- generation sequencing datasets to identify
specific and shared A3 regulatory factors. A combination of genetics, cell biology, virology,
biochemistry, and bioinformatics approaches will be used to delineate underlying molecular
mechanisms. These studies are anticipated to lead to novel strategies to therapeutically boost the
anti-HIV-1 activities of these enzymes and potentially contribute to a longer-term virus eradication
plan.
RELEVANCE (See instructions):
HIV/AIDS is still a pandemic problem. Targeted innate immune therapies have yet to be developed
against this virus. Fundamental research on molecular mechanisms regulating the antiviral APOBEC3
enzymes will stimulate the development of innovative HIV/AIDS therapeutics that work by leveraging
this innate immune defense system to extinguish virus replication.

## Key facts

- **NIH application ID:** 10077255
- **Project number:** 5R37AI064046-16
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Reuben S Harris
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $458,762
- **Award type:** 5
- **Project period:** 2004-12-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077255

## Citation

> US National Institutes of Health, RePORTER application 10077255, APOBEC3 Proteins in HIV Restriction (5R37AI064046-16). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10077255. Licensed CC0.

---

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