# HIV Host-Cell Interactions

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $523,059

## Abstract

Project Summary/Abstract
 The human immunodeficiency virus (HIV) is opposed by host cell factors, called “restriction factors”
with the potential to significantly control viral replication and affect disease progression and viral
transmission. Our hypothesis is that the critical balance between the activity of restriction factors and the
ability of the virus to antagonize or evade these factors plays in important role in HIV evolution, and
ultimately, our ability to cure this infection. While some restriction factors are very active against HIV, others
work poorly in humans or are polymorphic in the human population with both active and inactive versions.
In the APOBEC3 locus of restriction factors, APOBEC3H stands out because some humans make active
versions of this protein, while others do not, and a newly discovered polymorphism in APOBEC3C has
increased activity in a subset of humans. Antagonism of all of the APOBEC3 proteins is dependent on the
activity of the HIV-1 Vif protein which itself is polymorphic and must attack multiple host proteins at once.
 We will continue our studies on the interactions of restriction factors against HIV by determining the
consequences of virus going from individuals with differing repertoires of APOBEC3 proteins. We will use
an already established discordant couples cohort to understand the evolution and function of Vif proteins
when virus is transmitted from an individual with one APOBEC3H genotype to a person with a different
APOBEC3H genotype. In parallel, we will also exploit the natural infection of African Green Monkeys
(AGMs) subspecies with divergent SIVs to understand how polymorphism in the APOBEC3 locus affects
the evolution of the lentivirus-host relationship. In addition, we will determine the importance and
mechanism of a gain-of-function polymorphism in APOBEC3C. We will further study the evolutional
potential of Vif-APOBEC3 interactions by determining the steps needed for SIV Vif proteins to adapt to
antagonize the human APOBEC3 repertoire. Finally, we have initiated an innovative and flexible
CRISPR/Cas9 screen for novel restriction factors that will provide further insights into the interactions
between HIV and its host that affect virus replication. Overall, the goal of this proposal is to understand how
the evolution and function of these restriction factors impacts HIV replication in humans.

## Key facts

- **NIH application ID:** 9889015
- **Project number:** 5R01AI030927-29
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Michael Emerman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $523,059
- **Award type:** 5
- **Project period:** 1991-08-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889015

## Citation

> US National Institutes of Health, RePORTER application 9889015, HIV Host-Cell Interactions (5R01AI030927-29). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9889015. Licensed CC0.

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