Thursday, July 3, 2025 7/3/2025

Viral and Cellular Determinants of HIV-1 Assembly

Award Number: R01AI186611
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/20/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2029

Group Awards By:

View Award Description

Viral and Cellular Determinants of HIV-1 Assembly - The major goal of this application is to define viral interactions with host pathways that are essential for the assembly of infectious HIV-1 particles. We previously identified Rab11-FIP1C (FIP1C) as a key adaptor protein required for HIV-1 envelope protein (Env) trafficking and particle incorporation, a finding that established the model stating that host recycling pathways are required for particle incorporation. Recent work from our laboratory has extended this model, defining the role of KIF16B in Env trafficking and identifying discrete motifs within the Env cytoplasmic tail that are essential for recycling and particle incorporation. Preliminary data presented here now identifies the tubular recycling endosome (TRE) as a major new component of the recycling machinery involved in particle incorporation of Env. TRE components including MICAL-L1 and EHD1 were shown to be essential for Env trafficking and incorporation into particles. Remarkably, disruption of TRE trafficking severely depleted Env from particles, but only in those cells that have been shown to be nonpermissive for incorporation of cytoplasmic tail (CT)-depleted Env. Thus, this pathway holds the key to understanding the contribution of the Env CT to the recycling and particle incorporation of Env. Experiments in Aim 1 will define essential components of the TRE that contribute to Env trafficking, examining EHBP1, Rab10, Syndapin2, and MICAL-L1. In Aim 2, the critical role of EHD1-mediated scission from the TRE in Env trafficking to the PM site of assembly will be defined using cellular/biochemical and imaging approaches. A unique FAP-tagged Env construct will be employed to visualize and quantify Env trafficking from the TRE to the PM in live cells. Aim 3 will determine the mechanisms responsible for cell type- dependence of incorporation of Env, using a novel cell-cell fusion approach combined with identification of host factors that interact with the Env CT. Together, the work outlined here will expand upon a productive line of investigation that seeks to comprehensively define the mechanism of incorporation of Env into HIV-1 particles.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $609,012 )
2025	2025	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	2	4/14/2025	NON-COMPETING CONTINUATION	$609,012
														Subtotal = $609,012

Issue Date FY: 2024 ( Subtotal = $609,012 )
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	002	1	9/4/2024	NEW	$60,901
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	001	1	5/21/2024	NEW	$0
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	1	5/16/2024	NEW	$548,111
														Subtotal = $609,012

Grand Total All Awards = $1,218,024

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Viral and Cellular Determinants of HIV-1 Assembly

Award Number: R01AI186611

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/20/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer