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Analysis of the mechanism of HCMV cytoplasmic envelopment

Award Number: R01AI130156
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: 07/17/2017
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Analysis of the mechanism of HCMV cytoplasmic envelopment - Although largely asymptomatic, human cytomegalovirus (HCMV) can cause severe and even fatal disease in a subset of susceptible individuals. While great progress has been made in understanding essential stages of HCMV replication, a detailed description of many of these processes is lacking. Of particular interest in this proposal is the maturation of HCMV virions, namely tegument acquisition and cytoplasmic envelopment. To provide a molecular description of these events, it is important to identify the factors involved, both viral and cellular. This proposal will focus on two viral proteins, UL88 and UL71. We have previously published a role for UL88 in packaging a subset of tegument proteins into the virion tegument layer and the absence of UL88 decreases viral fitness. Previous work has identified UL71 as an envelopment factor that potentially mediates membrane scission, as viruses lacking UL71 are trapped at various stages of budding. The experiments in this proposal will seek to elucidate the molecular details of how UL88 and UL71 drive tegument acquisition and envelopment, respectively. This includes a detailed analysis of functional regions on each protein as well as an investigation into additional factors that potentially contribute to each process. We will investigate the role of EEA1+ endosomes in tegument acquisition and for the membrane scission factor DNM1 in cytoplasmic envelopment. This proposal will utilize a novel fluorescence-based envelopment to identify additional cellular proteins that participate in envelopment. Taken together, these studies will further our understanding of the molecular events that drive the late stages of HCMV maturation and identify novel ways in which HCMV assembly can be targeted as a potential intervention.


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 = $472,949 )
2025	2025	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	002	8	1/8/2025	NON-COMPETING CONTINUATION	$472,949
2025	2023	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	001	6	12/17/2024	COMPETING CONTINUATION	$11,640
2025	2021	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	000	5	12/17/2024	NON-COMPETING CONTINUATION	-$11,640
														Subtotal = $472,949

Issue Date FY: 2024 ( Subtotal = $487,577 )
2024	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	000	7	12/8/2023	NON-COMPETING CONTINUATION	$438,820
2024	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	001	7	5/20/2024	NON-COMPETING CONTINUATION	$48,757
														Subtotal = $487,577

Issue Date FY: 2023 ( Subtotal = $487,577 )
2023	2023	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	001	6	1/5/2023	COMPETING CONTINUATION	$487,577
2023	2023	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	002	6	3/24/2023	COMPETING CONTINUATION	$0
2023	2021	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	000	5	12/27/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $487,577

Issue Date FY: 2021 ( Subtotal = $378,312 )
2021	2021	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	000	5	6/17/2021	NON-COMPETING CONTINUATION	$378,312
														Subtotal = $378,312

Issue Date FY: 2020 ( Subtotal = $375,813 )
2020	2020	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY DR C1607	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	000	4	6/25/2020	NON-COMPETING CONTINUATION	$375,813
														Subtotal = $375,813

Issue Date FY: 2019 ( Subtotal = $378,640 )
2019	2019	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY DR C1607	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	000	3	6/12/2019	NON-COMPETING CONTINUATION	$378,640
														Subtotal = $378,640

Issue Date FY: 2018 ( Subtotal = $378,795 )
2018	2018	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY DR C1607	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	000	2	6/13/2018	NON-COMPETING CONTINUATION	$378,795
														Subtotal = $378,795

Issue Date FY: 2017 ( Subtotal = $373,616 )
2017	2017	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY DR C1607	HERSHEY	PA	17033	DAUPHIN	USA	Allergy and Infectious Diseases Research	000	1	7/17/2017	NEW	$373,616
														Subtotal = $373,616

Grand Total All Awards = $3,333,279

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Analysis of the mechanism of HCMV cytoplasmic envelopment

Award Number: R01AI130156

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: 07/17/2017

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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