Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Investigation of a novel mycovirus and its impacts on the biology and pathogenesis of Cryptococcus neoformans

Award Number: R21AI199262
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: 06/05/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2028

Group Awards By:

View Award Description

Investigation of a novel mycovirus and its impacts on the biology and pathogenesis of Cryptococcus neoformans - ABSTRACT. Cryptococcus neoformans is a significant human fungal pathogen that causes fatal cryptococcal meningoencephalitis, in both immunocompromised and immunocompetent patients. It has been designated a critical priority fungal pathogen by the World Health Organization due to its high mortality and treatment challenges. Our recent studies have revealed that loss of RNA interference (RNAi), a conserved genome defense system, is a relatively common event in C. neoformans. Yet the consequences of RNAi loss in natural populations remain poorly understood. Viruses that infect fungi (mycoviruses) are widespread in the fungal kingdom and have been found to alter fungal virulence, fitness, and gene expression. While mycoviruses have been extensively studied in the model yeast Saccharomyces cerevisiae and plant pathogens such as Cryphonectria parasitica, none had previously been identified in C. neoformans. We recently discovered the first known mycovirus in two C. neoformans RNAi-deficient clinical isolates. This virus belongs to double-stranded RNA totivirus (CnTV1), is of ~4.6 kb in length, and can be eliminated from the cells upon RNAi restoration, indicating that it is actively controlled by the fungal RNAi machinery. In this R21 application, we propose to define the molecular and functional impact of CnTV1 infection in C. neoformans. In Aim 1, we will characterize the sequence, structure, and localization of CnTV1 and identify fungal factors involved in its regulation. These include RNAi-dependent and -independent pathways such as the SKI complex and the exoribonuclease Xrn1. We will apply a combination of long-read RNA sequencing, Rapid Amplification of cDNA Ends (RACE), transmission electron microscopy, cryogenic electron microscopy, immunofluorescence, CRISPR genome editing, and RT-qPCR to dissect viral features and fungal control mechanisms. In Aim 2, we will determine how CnTV1 infection affects fungal virulence and host-pathogen interactions. Using isogenic strain pairs with and without the mycovirus CnTV1 (CnTV1+ and CnTV10), we will assess virulence in a murine model and evaluate immune responses through cytokine profiling in macrophage infection assays. Additionally, RNA-seq of both fungal and host cells will be conducted to define transcriptomic signatures associated with viral infection. These studies will reveal how CnTV1 contributes to fungal pathogenesis and immune modulation. This work will establish C. neoformans as a novel model for studying virus–fungus–host dynamics and provide fundamental insights into how mycoviruses shape the biology of human fungal pathogens. Findings from this project have the potential to uncover previously unrecognized determinants of fungal virulence and inform new strategies for antifungal therapeutic strategies.


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: 2026 ( Subtotal = $242,250 )
2026	2026	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	1	6/9/2026	NEW	$242,250
														Subtotal = $242,250

Grand Total All Awards = $242,250

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigation of a novel mycovirus and its impacts on the biology and pathogenesis of Cryptococcus neoformans

Award Number: R21AI199262

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: 06/05/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer