# Structural Basis of APOBEC Functions and HIV Restriction

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $412,602

## Abstract

Project Summary
Structural Basis of APOBEC Functions and HIV Restriction
 Apolipoprotein B mRNA-editing Enzyme Catalytic polypeptide (APOBEC) family of cytidine
deaminases are capable of deaminating the cytidine to cause mutation to uridine on DNA or RNA.
Human APOBEC deaminases have remarkable diverse cellular functions through specific targeting
to the intended ssDNA or RNA through a combination of regulations including spatial and temporal
distribution and substrate specificity. For example, APOBEC1 (A1) edits certain RNAs with the help
of specific cofactors to regulate cholesterol metabolism; AID has important role in acquired immune
response, it is required for antibody maturation including somatic hypermutation (SHM) and class
switch recombination (CSR); APOBEC2 (A2) is involved in cardiac and skeletal muscle
development; and APOBEC3 proteins (A3s, A3A-H) plays an important role in innate immunity for
anti-viral activity, they can restrict internal and external nucleic acids (such as RNA and DNA
viruses and retroelements) that poses danger to the genome integrity, which include internal
retroelements as well as external retroviruses and other infectious viral pathogens, such as
Hepatitis B Virus (HBV), Human Papillomavirus (HPV), and Human Immunodeficiency Virus (HIV).
Among APOBEC proteins, A3G/A3F/A3D/A3H display strong anti-HIV activity, which are through
deaminase-dependent and -independent mechanisms to inhibit viral replication and infection.
However, retroviruses like HIV-1 can overcome the anti-HIV activity of APOBEC enzymes by its
virus virulent factor (Vif) that specifically recruit cellular Cul5 E3 ligase to target these APOBECs for
ubiquitination and degradation, leading to the viral infection. The deamination activity of APOBECs
can also cause accidental genomic mutations, which can lead to various human diseases such as
immune deficiency and cancer.
 Our long-term scientific goals are to understand the structural/functional relationship for
APOBEC cellular functions and their anti-viral activities. Our specific aims are to understand the
structural basis of APOBEC’s functions and the mechanisms that underlie nucleic acid interactions,
multimerization, functional regulation, and viral restriction, with particular focuses on the double
domain APOBEC3 subfamily members that have strong anti-retroelements and anti-HIV activities.
The outcome of this research will provide valuable information for the fundamental molecular
mechanisms of APOBEC functions and their anti viral activities, which can be used for the potential
drug development to provide therapy for HIV/AIDS, immune disorders, and other diseases such as
cancer.

## Key facts

- **NIH application ID:** 10436802
- **Project number:** 5R01AI150524-11
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** XIAOJIANG S CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $412,602
- **Award type:** 5
- **Project period:** 2009-04-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436802

## Citation

> US National Institutes of Health, RePORTER application 10436802, Structural Basis of APOBEC Functions and HIV Restriction (5R01AI150524-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10436802. Licensed CC0.

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