# Viral and Cellular Determinants of HIV-1 Assembly

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $357,750

## Abstract

The major goal of this competing renewal is to define viral interactions with host pathways that are essential
for the assembly of infectious HIV-1 particles. HIV-1 particle assembly occurs on the plasma membrane of
infected cells. A major finding from this project was the identification of Rab11-FIP1C (FIP1C) as a key adaptor
protein required for HIV-1 envelope protein (Env) trafficking and particle incorporation. FIP1C-dependent
trafficking underlies the cell type-specific incorporation of Env, as disruption of a key motif in the cytoplasmic
tail (CT) involved in FIP1C translocation led to a loss of Env incorporation in cell types that was nearly identical
to that of CT-deleted viruses. Our recent data establish that Env traverses the endosomal recycling
compartment, where it meets FIP1C in a step required for subsequent outward trafficking and particle
incorporation of relevant primary isolate Envs. Simian Immunodeficiency Virus (SIV) Envs and a subset of
HIV Envs, in contrast, do not follow FIP1C-dependent trafficking in human cells. This competing renewal will
fully define the viral and host determinants of Env trafficking pathways. Experiments here will identify
additional members of the HIV-1 Env trafficking complex, including the essential kinesin mediating outward
sorting of Env. Experiments in this application will define the sequential steps in Env trafficking that lead to
the production of infectious viral particles, using a novel imaging strategy. FIP1C-mediated trafficking will be
characterized in primary monocyte-derived macrophages, where membrane dynamics and the intracellular
virus-containing compartment may introduce unique features. The essential role of FIP1C in the formation of
the virological synapse and in macrophage-to-T cell transmission events will then be delineated.

## Key facts

- **NIH application ID:** 9856444
- **Project number:** 8R01AI150486-23
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** PAUL W. SPEARMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,750
- **Award type:** 8
- **Project period:** 1997-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856444

## Citation

> US National Institutes of Health, RePORTER application 9856444, Viral and Cellular Determinants of HIV-1 Assembly (8R01AI150486-23). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856444. Licensed CC0.

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