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Elucidation of genetic networks of HSV-1 virion proteins and discovery of their functions in the morphogenesis of the infectious virus particle

Award Number: R01AI137365
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Herpesviruses are human pathogens that cause life-long persistent infections and result in clinical manifestations that range from a mild cold sore to cancer. Herpes simplex virus (HSV) is among the most frequently encountered virus by the general population. Infection with HSV-1 often results in orolabial disease but it can also cause ocular disease (keratitis) that can lead to blindness or encephalitis, which can be fatal. Type-2 infections are characterized by genital ulcerative disease and infections of the newborn. Thus, infections due to HSV are a major public health concern and understanding the biology of this virus is important in the development of efficacious treatments of these infections. The HSV-1 virion is comprised of four structural elements: a large double-stranded DNA molecule in the central core; an icosahedral capsid, which encloses the genome; a layer that immediately surrounds the capsid termed the tegument; and an outer membrane or envelope, which encloses the whole structure and in which are embedded the viral glycoproteins The tegument is one of the most complex and diverse structures of the virion, both in terms of protein composition and the functions encoded by the constituents of this structure. Of this large and diverse group of virion proteins, not all are classified as being essential for replication in a laboratory cell culture system. What are the functions of all the “non-essential” proteins for virion maturation and egress? These “accessory” gene products likely play important roles in the infected host but an in-depth discovery of their functions has not been accomplished in a comprehensive manner. Using a genome assembly line coupled with synthetic genomics methods, we can elucidate the functions of these proteins by creating “synthetic lethality” in a mutant virus. Our working hypothesis posits that by phenotypic investigation of synthetic lethals, we can then begin to formulate pathways in which these “redundant” virion proteins participate, as well as, their spatial/temporal roles during HSV-1 virion morphogenesis. The outcome of the proposed studies is expected to further our understanding of the roles of these multitude virion proteins and the importance of their interactions for infectious particle formation. The Specific Aims proposed to achieve these goals are: Specific Aim 1: Genetic interaction networks of the conserved tegument genes: Pivotal role of pUL21. Specific Aim 2: Elucidate the phenotypes of “synthetic lethals” that are centered around the abundant tegument protein, VP22 to determine pathways that lead to virus maturation and envelopment.


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: 2025 ( Subtotal = $0 )
2025	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	5	11/27/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $646,707 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	5	12/22/2023	NON-COMPETING CONTINUATION	$582,037
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	001	5	5/20/2024	NON-COMPETING CONTINUATION	$64,670
														Subtotal = $646,707

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	4	12/22/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $646,707 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	4	1/21/2022	NON-COMPETING CONTINUATION	$646,707
														Subtotal = $646,707

Issue Date FY: 2021 ( Subtotal = $646,707 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	3	12/17/2020	NON-COMPETING CONTINUATION	$646,707
														Subtotal = $646,707

Issue Date FY: 2020 ( Subtotal = $646,707 )
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	2	12/18/2019	NON-COMPETING CONTINUATION	$646,707
														Subtotal = $646,707

Issue Date FY: 2019 ( Subtotal = $662,644 )
2019	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	1	1/10/2019	NEW	$662,644
														Subtotal = $662,644

Grand Total All Awards = $3,249,472

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Elucidation of genetic networks of HSV-1 virion proteins and discovery of their functions in the morphogenesis of the infectious virus particle

Award Number: R01AI137365

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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