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Mechanism of Herpes Simplex Virus (HSV) Induced Membrane Fusion

Award Number: R01AI148478
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: 12/01/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Mechanism of Herpes Simplex Virus (HSV) Induced Membrane Fusion - Herpesviruses are associated with a variety of disease in the human host, ranging from asymptomatic infections to life threatening disease, including encephalitis and cancer. In addition to playing a direct role in cancer genesis, herpesviruses pose an increased risk to cancer patients who may develop debilitating and life- threatening herpesvirus infections. Genital herpes simplex virus (HSV) lesions, even if clinically not apparent, can facilitate the transfer of HIV-infected cells or free virus from one individual to another, and HIV infection and AIDS increase the risks of developing certain kinds of cancer. HSV-1 serves as a prototypic herpesvirus family member and provides an ideal model to understand the requirements for virus infection since it replicates well in cell culture and many reagents have been developed for its study. In particular, the study of HSV-1 entry has proven useful in the understanding the mechanism of Epstein-Bar Virus (EBV)and Kaposi Sarcoma Herpesvirus (KSHV) – two herpesviruses associated with cancer in human infections. Herpesvirus entry into cells requires fusion of the outer envelope of the virus with a cell membrane. Spread of infection can occur via infectious virus or virus-induced cell fusion. The ultimate objective of studies described here is to understand how herpesviruses, specifically HSV-1, induce membrane fusion, the process required for viral entry and cell fusion. Requirements for HSV-induced membrane fusion include the coordinated activities of four HSV glycoproteins (gD, the hererodimeric gHgL complex, and gB) and specific cellular receptors. Our central hypothesis is that gD, present in the viral envelope or on an infected cell surface, binds to a cellular receptor, such as nectin-1, on an uninfected cell and activates gHgL and gB via protein-protein interactions, resulting in fusion mediated by gB. In three aims, we plan to define the sequence requirements and domains of gD, gH/gL and gB that are required to mediate membrane fusion and to investigate means to stabilize gB so that prefusion gB can be studied. The results of these studies will lead to an understanding of the mechanism of herpesvirus-induced membrane fusion and to new approaches for the prevention and treatment of herpesvirus infections.


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 = $0 )
2026	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	5	12/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $546,894 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	001	5	5/16/2024	NON-COMPETING CONTINUATION	$54,689
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	5	11/7/2023	NON-COMPETING CONTINUATION	$492,205
														Subtotal = $546,894

Issue Date FY: 2023 ( Subtotal = $546,894 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	4	11/30/2022	NON-COMPETING CONTINUATION	$546,894
														Subtotal = $546,894

Issue Date FY: 2022 ( Subtotal = $546,894 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	3	11/19/2021	NON-COMPETING CONTINUATION	$546,894
														Subtotal = $546,894

Issue Date FY: 2021 ( Subtotal = $591,741 )
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	2	11/13/2020	NON-COMPETING CONTINUATION	$591,741
														Subtotal = $591,741

Issue Date FY: 2020 ( Subtotal = $555,984 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	1	11/29/2019	NEW	$555,984
														Subtotal = $555,984

Grand Total All Awards = $2,788,407

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Mechanism of Herpes Simplex Virus (HSV) Induced Membrane Fusion

Award Number: R01AI148478

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: 12/01/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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