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Coxiella burnetii effector CBU1198 inhibits JAK1 to downregulate interferon signaling during infection

Award Number: F30AI194824
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 11/09/2026
PERIOD OF PERFORMANCE END DATE: 11/08/2027

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Coxiella burnetii effector CBU1198 inhibits JAK1 to downregulate interferon signaling during infection - Project Summary Coxiella burnetii (Cb), an obligate intracellular gram-negative pathogen, is the causative agent of ﬂu-like syndrome Q fever. Typically transmitted by inhalation route, Cb preferentially infects alveolar macrophages (AM) before disseminating to secondary sites like the liver, heart, and spleen. Occasionally, infected individuals develop chronic Q fever presenting as endocarditis, osteomyelitis, or hepatitis. Notably, Cb releases over 100 eﬀector proteins, each with unique roles in the manipulation of the intracellular environment to maximize bacterial replication and minimize immune surveillance. The proposed studies will investigate the role of hypothetical eﬀector CBU1198 inhibiting interferon signaling in AM, the natural Cb infective niche. While there are many diﬀerent types of interferon, Types I and II are commonly associated with the viral response in mammalian cells. More recently, literature shows that intracellular bacteria, including Cb, are also negatively regulated through the stimulation of these pathways. Given the unique ability of Cb to inhibit multiple components of the innate immune signaling pathway, the interferon signaling cascade is a reasonable but yet unpublished target for Cb eﬀectors. Speciﬁcally, Type I and II Interferon share a protein, Janus Kinase 1 (JAK1), as a critical component of their receptors that potentiates downstream STAT1/2 phosphorylation and therefore nuclear localization. The proposed studies will investigate the role of Cb eﬀector CBU1198 as an inhibitor of JAK1 and more broadly intracellular interferon signaling. Preliminary studies indicate eﬀector-dependent inhibition of STAT1 phosphorylation and CBU1198-dependent downregulation of iNos transcript in murine AM (mAM), and pulldown experiments in constitutively expressing CBU1198 RAW 264.7 indicate JAK1 as a potential binding partner for CBU1198. The hypothesis is that CBU1198 inhibition of JAK1 activity is critical to Cb intracellular replication and that this observation is maintained in both a virulent Cb strain and in human AM (hAM) studies. Aim 1: Demonstrate the role of CBU1198 as a JAK1 inhibitor to downregulate Type I/II Interferon signaling during Cb infection Aim 2: Test the impact of CBU1198 on interferon signaling in hAM during Cb infection Aim 3: Analyze role of CBU1198 in virulent Cb strains using in vitro and in vivo models These experiments will deﬁne the activity of CBU1198 as well as its proposed binding to JAK1 using primary mouse and human cells as well as examine the impact of the eﬀector protein in a virulent Cb model. The training plan focuses on providing opportunities to learn pulmonology procedures, gaining insight into the ﬁeld, and joining those experiences with a clinically relevant model in an understudied pulmonary pathogen, all of which align with the student’s goal of pursuing a physician-scientist career in pulmonology.


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 = $38,708 )
2026	2026	TEXAS A & M UNIVERSITY SYSTEM HEALTH SCIENCE CENTER	6003 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	000	1	5/11/2026	NEW	$38,708
														Subtotal = $38,708

Grand Total All Awards = $38,708

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Coxiella burnetii effector CBU1198 inhibits JAK1 to downregulate interferon signaling during infection

Award Number: F30AI194824

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 11/09/2026

PERIOD OF PERFORMANCE END DATE: 11/08/2027

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