# HARC: HIV accessory and regulatory complexes

> **NIH NIH U54** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $6,603,997

## Abstract

THE HARC CENTER: HIV ACCESSORY AND REGULATORY COMPLEXES
OVERALL SUMMARY
The HARC Center is an interdisciplinary program that aims to improve our understanding of the interactions
between HIV accessory and regulatory proteins and host cellular systems, with the ultimate goal to expand on
therapeutic targets and treatment modalities for HIV/AIDS. The HARC Center will focus its efforts on the
determination of structures of the accessory and regulatory proteins of HIV-1, with a focus on Tat, Vif and Rev,
in complex with their cellular partners, which have not been targets of HIV therapeutic modalities until now. A
better molecular understanding of the functions and mechanisms of virus-host complexes may reveal new
therapeutic strategies for intervention, including strategies of host-directed therapies, which may escape the
limitations of current drug regimens where mutations in the targeted HIV enzymes can diminish drug efficacy.
The HARC Center will determine the structures of these virus-host complexes using an integrated “Systems-to-
Structure” platform that includes (1) Discovery, through novel methods of functional proteomics and genetics
being developed in the HARC Center, (2) Validation through breakthrough CRISPR methods in primary T cells
as well as targeted biochemical and functional assays, and (3) Structure Determination using a synthesis of
innovative structural techniques developed in previous iterations of the HARC Center to address the large,
flexible, heterogeneous and sometimes membrane-associated systems we study.
The proposed Research Projects are centered around three themes that serve the Center’s goal. We will explore
how HIV inhibits Host restriction factors (Theme 1), study the factors regulating HIV transcription and latency
(Theme 2) and investigate virus-host Evolution (Theme 3) across three projects: Structure and evolution of Vif
and APOBEC3 (Project 1), Regulation of HIV transcription and latency (Project 2), and Genetics and
evolution (Project 3). The HARC Center projects are supported by 4 technology cores covering proteomic
approaches (Core 1 - Proteomics), CRISPR screens and endogenous tagging in primary cells to study virus-
host function (Core 2 - Genetics), structural biology using cryo-Electron Microscopy, X-ray screening and
antibody technologies to determine the structures of HIV virus-host complexes (Core 3 - Structural Biology),
and integrative modeling of virus-host complexes (Core 4 - Computational). The overall goals, progress, and
administration as well as outreach activities and communications will be overseen by the Administrative Core
(Core 5). The Developmental Core (Core 6) will provide training opportunities to young investigators and HARC
Center members and award the Collaborative Opportunity Fund to enhance the Center’s overall research theme.

## Key facts

- **NIH application ID:** 10666644
- **Project number:** 5U54AI170792-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Nevan J Krogan
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $6,603,997
- **Award type:** 5
- **Project period:** 2022-07-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10666644

## Citation

> US National Institutes of Health, RePORTER application 10666644, HARC: HIV accessory and regulatory complexes (5U54AI170792-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10666644. Licensed CC0.

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