# HARC Center: HIV Accessory and Regulatory Complexes

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $4,808,425

## Abstract

CENTERS FOR HIV/AIDS-RELATED STRUCTURAL BIOLOGY (P50)
HARC CENTER: HIV ACCESSORY AND REGULATORY COMPLEXES
OVERALL SUMMARY
The HARC Center is an integrated program proposed by investigators whose overarching goal is to improve
understanding of the interactions between HIV accessory and regulatory proteins and host cellular systems to
enable eventual expansion of therapeutic approaches. There are currently no HIV therapeutics targeting any
of the proteins on which the HARC Center is focused (HIV-1 Vif, Vpu, Nef, Tat and Rev proteins and their
interacting viral and cellular partners). The scientific focus of the Center is on determining structures of these
complexes, using an integrated Systems to Structure pipeline 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 in vivo and in vitro functional assays, and
(3) Structure Determination using a synthesis of innovative structural techniques developed in the HARC
Center to address the large, flexible, heterogeneous and sometimes membrane-associated systems we study.
We are focused on two themes aimed at understanding the biological questions surrounding HIV replication
and persistence in the host cell. These include how the virus counteracts host restriction mechanisms (Theme
1: “Counteracting”) and how the virus hijacks host systems for viral transcription and RNA export/trafficking
to ensure continuation of the viral life cycle (Theme 2: “Hijacking”). The seven projects proposed here
include: (1) Structure and Evolution of APOBEC3-Vif Interactions, (2) Regulation of Vif and Rewiring of Host
Pathways, (3) The Multiple Functions of Vpu at the Membrane, (4) Nef Interaction Networks at the Membrane,
(5) Tat-Host Transcription Complexes, (6) Structure and Dynamics of Rev and RNA-Host Complexes, and (7)
Characterization of “Super Restriction Factors” and Prediction of Host-HIV Interfaces. The HARC Center
projects are supported by an administrative core and seven technology cores essential for their completion: (1)
Proteomic Approaches to HIV Function, (2) CRISPR in Primary Cells to Study HIV-Host Function, (3)
Molecular Imaging Using Cryo-Electron Microscopy (EM), (4) Application and Development of Antibody Tools,
(5) Integrative Modeling of HIV-Human Complexes, (6) X-ray Screening and Rapid Structure Determination,
and (7) Membrane Protein Expression/Purification.
We are committed to collaborating with Sister Centers and the HIV research community as well as training the
next generation of investigators. We create and support opportunities including the Technology Training
Residency to bring young investigators to learn in our Center's Cores, and we seed new research through the
Collaborative Opportunity Fund, along with holding events such as seminars and an annual symposium.

## Key facts

- **NIH application ID:** 10229558
- **Project number:** 5P50AI150476-15
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Nevan J Krogan
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $4,808,425
- **Award type:** 5
- **Project period:** 2007-08-27 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229558

## Citation

> US National Institutes of Health, RePORTER application 10229558, HARC Center: HIV Accessory and Regulatory Complexes (5P50AI150476-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10229558. Licensed CC0.

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