# The Vif-APOBEC Nexus

> **NIH NIH K99** · UNIVERSITY OF MINNESOTA · 2020 · $102,152

## Abstract

THE VIF-APOBEC NEXUS
ABSTRACT: The discovery of the antiviral APOBEC3 (A3) enzymes is one of the most therapeutically promising
breakthroughs in HIV/AIDS molecular virology because of the direct and potent nature of their virus restriction
activities. Four different A3 enzymes have the ability to package into nascent HIV-1 particles and restrict the
virus by physically interfering with the progression of reverse transcription and deaminating viral cDNA cytosines
to uracils. A3 catalysis of C-to-U lesions in minus strand viral cDNA is the defining hallmark of A3-mediated
restriction, explaining genomic plus strand G-to-A mutations in patient-derived viral sequences. However, the
virus deploys a counteraction strategy that utilizes the virus encoded “virion infectivity factor” (Vif) to
polyubiquitinate and degrade the A3s through a cellular E3-ubiquitin ligase complex. Here, I will use robust and
unbiased experimental approaches to 1) delineate the molecular surfaces used by Vif to recognize and degrade
the restrictive A3s and 2) define the cellular mechanisms that regulate anti-HIV-1 activity of the A3s. My studies
will utilize both hypothesis- and technology-driven approaches and a combination of fundamental virology,
genetics/genome engineering, cell biology, and biochemistry techniques. I anticipate that a better understanding
of the Vif/A3 surfaces and the underlying cellular mechanisms that govern A3 antiviral activity has the potential
to lead to novel strategies to boost the anti-HIV-1 activities of these enzymes and contribute to the overall NIAID
priority of “supporting innovative strategies for treating or curing HIV infection.”

## Key facts

- **NIH application ID:** 9989775
- **Project number:** 5K99AI147811-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Daniel James Salamango
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $102,152
- **Award type:** 5
- **Project period:** 2019-08-06 → 2021-04-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989775

## Citation

> US National Institutes of Health, RePORTER application 9989775, The Vif-APOBEC Nexus (5K99AI147811-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989775. Licensed CC0.

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