# HIV-1 Preintegration Trafficking and Nuclear Localization

> **NIH NIH R01** · DANA-FARBER CANCER INST · 2021 · $499,291

## Abstract

SUMMARY
Intensive efforts in recent years have been devoted to the discovery of a widely applicable anti-HIV/AIDS
vaccine or functional cure. Though these efforts continue, the hope of reaching either goal in the near future
seems dim. By contrast, combination antiretroviral therapy has over the past 20 years in large part kept HIV-1
in check from running rampant worldwide. Despite this medical milestone, significant numbers of new
infections each year initiate from drug resistant viral strains, and many of the utilized drugs have unwanted side
effects. New combinatorial formulations are therefore required to stay ahead of the virus for the foreseeable
future. A vast repertoire of largely untapped drug targets stem from the multitude of specific interactions the
virus must make with the host cell in order to support its replication. After HIV-1 enters a new cell, the viral
RNA genome is converted into a linear DNA molecule by reverse transcription. The resulting preintegration
complex, which is composed of the viral DNA as well as viral and host proteins, traffics along microtubules to
the cell nucleus, where it is transported into the nucleus in an energy-dependent manner. Once inside, the
preintegration complex traffics to active genes, which are the sites of preferential HIV-1 integration. Using a
variety of molecular biology, virology, biochemistry, cell biology, and bioinformatic approaches, this basic
science grant will discover and characterize virus-host interactions that are critical for the steps of
preintegration complex nuclear import and subsequent intranuclear trafficking to the sites of viral DNA
integration. Such information will critically inform downstream programs that aim to target these essential steps
of the HIV-1 replication cycle for drug discovery.

## Key facts

- **NIH application ID:** 10101602
- **Project number:** 5R01AI052014-19
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Alan N. Engelman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $499,291
- **Award type:** 5
- **Project period:** 2003-01-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101602

## Citation

> US National Institutes of Health, RePORTER application 10101602, HIV-1 Preintegration Trafficking and Nuclear Localization (5R01AI052014-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10101602. Licensed CC0.

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