# Determining the role of microtubules and motor proteins during early HIV-1 replication

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $242,404

## Abstract

Determining the role of microtubules and motor proteins during early HIV-1 replication
SUMMARY
During HIV-1 infection, viral membrane fuses with the host cell membrane to deliver the HIV-1 virus to the host
cell cytoplasm. Once within the cell, HIV-1 must translocate to the nucleus for the reverse transcribed DNA to
be incorporated into the host genome. Despite 40+ years of research devoted to HIV-1 infection, surprisingly
little is known about how HIV-1 exploits the host cell cytoskeleton to facilitate transport to the nucleus and
accelerate infection. The goal of this proposal is to establish and validate an assay to measure HIV-1
microtubule trafficking in vitro via kinesin and dynein microtubule motor proteins. Recent work has led to the
identification of two host factors - FEZ1 and BicD2 - that serve as cargo adaptors for transport via kinesin-1
and cytoplasmic dynein-1, respectively. To study the role of FEZ1 and BicD2 in the transport of HIV-1, we will
utilize single-molecule total internal reflection fluorescence (TIRF) microscopy to monitor the transport of
fluorescently-labeled virus-motor complexes on reconstituted microtubules (Aim 1). We will use a novel
synthetic icosahedral scaffold derived from encapsulins to validate the assay, which we will use to measure the
motility of motor protein teams bound to viral cargo via cargo adaptors. We will then determine how HIV-1
determines directionality on microtubules (kinesin vs. dynein) by measuring the combined influences of FEZ1,
BicD2, kinesin-1, and dynein (Aim 2). By establishing that microtubule motors are capable of transporting
HIV-1 in vitro, this proposal will provide a new avenue in the study of HIV-1 and provide new targets to block
HIV-1 infection.

## Key facts

- **NIH application ID:** 10161131
- **Project number:** 1R21AI152869-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Michael Cianfrocco
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $242,404
- **Award type:** 1
- **Project period:** 2021-08-18 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10161131

## Citation

> US National Institutes of Health, RePORTER application 10161131, Determining the role of microtubules and motor proteins during early HIV-1 replication (1R21AI152869-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10161131. Licensed CC0.

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