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Hepatitis B virus e antigen in viral persistence

Award Number: R37AI129540
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: 02/20/2017
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Hepatitis B virus e antigen in viral persistence - Abstract Hepatitis B virus (HBV) is one of the most important human pathogens. There are approximately 300 million chronic HBV carriers in the world, resulting in nearly 1 million deaths every year. Most chronic HBV carriers acquired the virus from their infected mother early in life. HBV has a very narrow host range, which has greatly hampered its research. By crossing female hemizygous HBV transgenic mice that carry the 1.3mer overlength HBV genome to male naïve mice, we had developed a mouse model to study the mechanism of HBV persistence. We found that the persistence of HBV in mice was dependent on the HBV e antigen (HBeAg) and Kupffer cells, the resident macrophages of the liver. The requirement of HBeAg for HBV persistence is consistent with the clinical observation that the HBV persistence in babies is dependent on the HBeAg-positivity of their mothers. Our recent studies revealed an interesting interplay between HBeAg and hepatic macrophages. This interplay can either promote the HBV persistence or HBV clearance. In this application, we will continue to study this interplay between HBeAg and macrophages to understand the mechanism of HBV persistence. We had recently discovered that HBeAg could reprogram the metabolism of macrophages to promote the oxidative phosphorylation (OXPHOS). This metabolic reprogramming by HBeAg appears to be important for the attenuation of pro-inflammatory activities of Kupffer cells. We will therefore continue to study how HBeAg reprograms the metabolism of macrophages and study the implication of this reprogramming in the anti-HBV response. Our preliminary results also indicated that the toll-like receptor 4 (TLR4) mediated the effects of HBeAg on Kupffer cells. Thus, we will also investigate whether TLR4 serves as the receptor of HBeAg and its role in HBV persistence. Finally, we will determine whether HBeAg by itself is sufficient to promote HBV persistence and whether HBeAg can train Kupffer cells in utero to promote HBV persistence. Our proposed studies will provide important information for us to understand the mechanism of HBV persistence and help to improve the treatments for chronic HBV patients.


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 = $495,000 )
2026	2026	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	9	1/28/2026	NON-COMPETING CONTINUATION	$495,000
														Subtotal = $495,000

Issue Date FY: 2025 ( Subtotal = $495,000 )
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	8	2/28/2025	NON-COMPETING CONTINUATION	$495,000
														Subtotal = $495,000

Issue Date FY: 2024 ( Subtotal = $676,548 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Allergy and Infectious Diseases Research	002	7	5/23/2024	NON-COMPETING CONTINUATION	$49,500
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	7	1/17/2024	NON-COMPETING CONTINUATION	$445,500
2024	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	6	2/9/2024	COMPETING CONTINUATION	$181,548
														Subtotal = $676,548

Issue Date FY: 2023 ( Subtotal = $495,000 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	6	2/3/2023	COMPETING CONTINUATION	$495,000
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	6	8/1/2023	COMPETING CONTINUATION	$0
														Subtotal = $495,000

Grand Total All Awards = $2,161,548

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Hepatitis B virus e antigen in viral persistence

Award Number: R37AI129540

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: 02/20/2017

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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