# Characterization of Super Restriction Factors and Prediction of Host-HIV Interfaces

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $492,324

## Abstract

The human genome has evolved a constellation of antiviral genes with the potential to target HIV. However,
the efficacy of these antiviral proteins fluctuates dynamically in evolutionary terms; evolution of the viruses
triggers evolution of host components and vice-versa. For instance, HIV has adapted to grow in human cells,
in part, because it has adapted to escape human antiviral inhibition. In this project, the evolutionary signatures
of past interactions of lentiviruses with their primate hosts will be used to guide functional and structural studies
of HIV-host protein interactions.
In particular, this project exploits genetic innovation at the host-virus interface, characterized by signatures of
recurrent Darwinian selection, or positive selection. We use evolutionary signatures of such genetic innovation
to derive “super restriction factors” that are more potent at inhibiting HIV and less susceptible to antagonism by
viral proteins. By testing libraries of host restriction factors with random amino acid changes at the sites of
positive selection, host proteins with novel properties can be derived. Finally, using the criterion of positive
selection, a whole genome catalog will be created that will be used to prioritize candidate host proteins
identified as part of genome-wide genetic screens or protein-protein interaction studies for further biochemical
studies in other Projects in this application by providing a means of assessing if these interactions have been
involved in past evolutionary conflicts with pathogens.

## Key facts

- **NIH application ID:** 9993247
- **Project number:** 5P50AI150476-14
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Michael Emerman
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $492,324
- **Award type:** 5
- **Project period:** 2007-08-27 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993247

## Citation

> US National Institutes of Health, RePORTER application 9993247, Characterization of Super Restriction Factors and Prediction of Host-HIV Interfaces (5P50AI150476-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9993247. Licensed CC0.

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