# Project 5:  Structural investigation of lentiviral DNA integration

> **NIH NIH P50** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $102,600

## Abstract

P5. Abstract
Retroviral replication depends on integration of reverse transcribed viral DNA into a host cell chromosome. This
process is catalyzed by integrase (IN) in the context of a stable synaptic complex, known as the intasome. The
intasome is the target for IN strand transfer inhibitors (INSTIs), the only class of HIV IN antagonists currently
approved to treat HIV/AIDS. Recent years saw characterization of the intasomes from several retroviral species,
collectively elucidating the conserved intasomal core assembly (CIC) responsible for integration. We have now
established the first lentiviral intasome model based on maedi-visna virus (MVV), which affords detailed
structural studies of lentiviral integration in the absence of solubilizing or hyperactivating mutations in IN. The
preliminary study of the MVV intasome by single particle cryo-EM in the Cherepanov laboratory revealed that it
is much larger than its non-lentiviral counterparts, comprising a hexadecamer (tetramer-of-tetramers) of IN. In
the proposed project we take advantage of the new system to study lentiviral DNA integration into chromatin
and the role of the host cell factor LEDGF/p75 in this process. As a translational component of this project, we
will develop a lentiviral intasome model for structural studies of INSTIs and the mechanisms of drug resistance.

## Key facts

- **NIH application ID:** 9977957
- **Project number:** 5P50AI150481-14
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Peter Cherepanov
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $102,600
- **Award type:** 5
- **Project period:** 2007-08-27 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977957

## Citation

> US National Institutes of Health, RePORTER application 9977957, Project 5:  Structural investigation of lentiviral DNA integration (5P50AI150481-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977957. Licensed CC0.

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