Monday, June 30, 2025 6/30/2025

Identification of evolutionarily conserved pro-viral and anti-viral host factors from worms to mammals

Award Number: R21AI180837
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: 11/17/2023
PERIOD OF PERFORMANCE END DATE: 10/31/2025

Group Awards By:

View Award Description

Identification of evolutionarily conserved pro-viral and anti-viral host factors from worms to mammals - ABSTRACT Viruses are obligate intracellular parasites that have evolved to co-exist with their hosts. As such, they have the ability to both hijack the necessary host machinery to promote viral proliferation as well as to antagonize host immune defenses. Despite extensive research in these areas there are still significant gaps in our knowledge of the repertoire of host genes that function in either pro-viral or anti-viral manner. A novel strategy to identify host genes that are important for mammalian virus infection takes advantage of the model organism C. elegans. Due to its simplicity and the fact that ~40% of its genes (~7500) are conserved with humans, C. elegans has played a key role in many fundamental discoveries in biology. However, its use in the study of virology had been limited by the lack of known viruses capable of naturally infecting C. elegans until the discovery in 2011 of Orsay Virus. Orsay virus is a non-enveloped positive sense RNA virus related to viruses in the families Picorna-, Calici- and Astroviridae, and thus it can serve as a model for many pathogenic mammalian viruses. Several published studies have demonstrated clear proof of concept that the Orsay virus-C. elegans model can be used to identify novel genes important for infection by mammalian viruses. For some genes that are absolutely required for Orsay virus infection in C. elegans, knockouts of the orthologous gene in human cell culture result in up to ~1,000-fold reductions in virus titers for viruses like encephalomyocarditis virus (EMCV) and Coxsackie Virus B3 (CVB3). To systematically identify genes that promote or antagonize Orsay virus infection in C. elegans, a large-scale RNAi screen will be performed. RNAi in C. elegans is both more facile and robust than corresponding siRNA screening in mammalian cells, and it is complementary to CRISPR screens in cell culture. The goals of this project are: (1) To systematically identify host factors that impact Orsay virus infection in C. elegans by performing RNAi against the ~ 7500 C. elegans genes with human orthologs. (2) Determine whether the human orthologs of genes identified in Aim 1 play roles in infection by a panel of mammalian viruses. This study will identify, in an unbiased fashion, novel genes with pro-viral and anti-viral functions.


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 = $226,253 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	2	1/14/2025	NON-COMPETING CONTINUATION	$226,253
														Subtotal = $226,253

Issue Date FY: 2024 ( Subtotal = $194,375 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	1	11/17/2023	NEW	$174,938
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	001	1	9/12/2024	NEW	$19,437
														Subtotal = $194,375

Grand Total All Awards = $420,628

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Identification of evolutionarily conserved pro-viral and anti-viral host factors from worms to mammals

Award Number: R21AI180837

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: 11/17/2023

PERIOD OF PERFORMANCE END DATE: 10/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer