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The Role of Type I Interferon in Murine Roseolovirus Induced Autoimmune Gastritis

Award Number: F30AI197461
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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The Role of Type I Interferon in Murine Roseolovirus Induced Autoimmune Gastritis - PROJECT SUMMARY/ABSTRACT. Viral triggers of autoimmune disease remain poorly understood and have been hypothesized to contribute as initial triggers of the immune disturbances that underlie clinical autoimmunity as well as promoters of disease. Human Roseoloviruses, Human Herpesvirus (HHV)-6 and 7, have been associated with several autoimmune diseases notably encephalitis, and multiple sclerosis (MS). Due to high species-specific tropism, human herpesviruses are difficult to study in a controlled environment, and their relationship with the development of these disorders remains elusive. Recently however, the murine roseolovirus (MRV) was identified and found to be a close homolog of HHV-6 and 7. MRV is a thymotropic virus that causes transient, severe thymic atrophy with the most pronounced loss occurring in CD4/CD8 double-positive (DP) and CD4 single-positive (SP) thymocytes. Single-cell RNA sequencing data shows that CD4 SPs, DPs and double negative (DN) thymocytes as well as medullary thymic epithelial cells (mTECs) can support productive infection of MRV. Neonatal infection of mice with MRV causes autoimmune gastritis (AIG) in adulthood. CD4 T cells are both required and sufficient for AIG development in this model. MRV infections also results in loss of AIRE transcripts in mTECs, and development of autoantibodies to several tissue antigens targeting almost all organ systems. Additionally, type I interferon (IFN) signaling is required for development of AIG in neonatally infected mice. The goal of this study is to understand the role of type I IFN signaling in auto-immune gastritis development in the setting of neonatal MRV infection. We hypothesize that type I IFN is a major contributor in the disruption of central tolerance, specifically leading to alterations in T cell selection and development of autoreactive T cells, as well as an aberrant T regulatory cell (Treg) response. I will investigate whether type I IFN is required for the development of autoreactive T cells and whether type I IFN leads to disruptions in Treg development. Using a unique model of virus-induced autoimmunity, our study has the potential to shed light on the infectious triggers of the immune disturbances observed sometimes years prior to clinical symptoms, providing insight into the early mechanisms underlying autoimmune disease onset. As an MD/PhD student, my long-term goal is to become a physician-scientist leading a research lab in dermatology. Completion of this project will equip me with a strong foundation at the intersection of immunology, virology, and autoimmunity, fields that often converge in skin-related clinical presentations. My robust training plan at WashU in St Louis, one of the nation's leading MD/PhD programs integrates strong mentorship, rigorous coursework, independent study, and participation in research meetings ranging from local to international. This tailored approach is designed to support the successful execution of my research proposal and to position me for long-term success in achieving my career goals.


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 = $37,249 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	1	4/1/2026	NEW	$36,673
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	002	1	4/24/2026	NEW	$576
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	1	4/10/2026	NEW	$0
														Subtotal = $37,249

Grand Total All Awards = $37,249

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The Role of Type I Interferon in Murine Roseolovirus Induced Autoimmune Gastritis

Award Number: F30AI197461

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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