# Structurally dissecting APOBEC3's for HIV-1 restriction and beyond

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $674,415

## Abstract

Structurally dissecting APOBEC3s for HIV-1 restriction and beyond
The human immune system protects us against pathogens but can cause problems when
the system goes awry. Implicated in both innate and adaptive immunity, the AID/APOBEC
family of enzymes are cytidine deaminases with differential roles of still limited
understanding. A subset of APOBEC3s (A3s) were initially discovered to potently restrict
HIV-1, including A3G, A3F and A3H. These restrictive enzymes are so potent that HIV
evolved the “virion infectivity factor” protein Vif to counter this restriction by hijacking an E3
ubiquitin ligase and specifically targeting A3s for degradation. Subsequent research has
revealed that A3’s ability to respond and restrict viral infection is by inducing
hypermutations in the viral genome, which is not limited to HIV but extends to other
retroviruses and retrotransposons. A3s also restrict DNA viruses, including nuclear
replicating ssDNA viruses such as adeno-associated virus and dsDNA viruses such as
hepatitis B virus, herpes viruses and HPV. However, A3 activity can be a double-edged
sword. If not properly regulated, DNA-editing APOBECs that also have access to the
nucleus can deaminate self-genomes, potentially instigating cancer. When overexpressed,
A3A, A3B and A3H have been described as a major endogenous source for mutations in
various types of human cancer, such as breast, bladder, head and neck, cervical, and lung
cancer. We hypothesize that A3s have unrealized therapeutic potentials, both as anti-viral
targets through reactivating the natural anti-HIV function by blocking Vif binding and as
targets for chemotherapy to restrict the genome diversity within tumors. In this proposal we
are leveraging our complementary strengths through a multi-disciplinary approach combining
structural biology, biophysics, enzymology, chemistry and virology, to characterize the
molecular interactions and differential specificities of A3s to nucleic acids and HIV-1 Vif, which
will provide epitopes that once characterized will be target sites for future therapeutic
development.

## Key facts

- **NIH application ID:** 10167632
- **Project number:** 5R01AI150478-06
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Celia A. Schiffer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $674,415
- **Award type:** 5
- **Project period:** 2016-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167632

## Citation

> US National Institutes of Health, RePORTER application 10167632, Structurally dissecting APOBEC3's for HIV-1 restriction and beyond (5R01AI150478-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10167632. Licensed CC0.

---

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