Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Structural basis of human cytomegalovirus replication within host cells

Award Number: R01DE028583
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2030

Group Awards By:

View Award Description

Structural basis of human cytomegalovirus replication within host cells - PROJECT SUMMARY/ABSTRACT Human cytomegalovirus (HCMV) is a ubiquitous human herpesvirus found in up to 90% of adults. Active HCMV infection (often referred to simply as CMV by clinicians) can manifest as chronic oral ulcerations and sialadenitis, and is a major viral cause of birth defects and life-threatening conditions in immunosuppressed individuals. HCMV is largely innocuous in healthy adults, but for newborns and the immune-compromised, such as those with AIDS or organ transplant recipients, the dearth of effective HCMV therapies or vaccines poses a grave risk. HCMV, a member of the β-herpesvirus subfamily of the Herpesviridae, is the most structurally and genetically complex herpesvirus (e.g., its genome is twice that of chickenpox-causing varicella zoster virus, an α-herpesvirus). Architecturally similar to other herpesviruses, HCMV virion consists of four concentric, largely pleomorphic layers: a glycoprotein-decorated envelope, a large, ill-defined tegument layer, and a bacteriophage-like icosahedral capsid enclosing a dsDNA genome of 230,000 base pairs. In the current funding cycle, the PI’s group published the cryogenic electron microscopy (cryoEM) and tomography (cryoET) structures of these layers of HCMV and related β-herpesviruses (human herpesvirus 6 and murine cytomegalovirus) in a series of high-impact papers and discovered two live-attenuated mutants through structure-guided mutagenesis with co-I Tang lab (vaccine patent pending). Among them are the first in situ structures of gB and gB-gH/gL complexes on the HCMV envelope, the atomic structures of the genome- translocating portal complex, capsid-associated tegument proteins of HCMV and other herpesviruses, as well as human tRNA bound to the HCMV-specific tegument phosphoprotein, pp150. The renewal application builds on these successes and harness the PI’s machine learning-empowered cryoEM and cryoET technologies, and the co-I’s complementary virology expertise, to determine the native structures of the so-far poorly defined phosphorylated tegument proteins and tRNA interaction in HCMV and to explore their potential roles in CMV infections. Our central hypothes is that HCMV packages a myriad of molecules—including human tRNA and switchable phosphoproteins—and release them to modulate immune systems and promote replication within host cells. First, we will define cell-line specific recruitment of human tRNA by the CMV-specific tegument protein pp150 and explore the roles of virion-containing human tRNA in replication (Aim 1). Second, we will obtain native atomic structures of pp65, pp71 and by structure-guided mutagenesis, elucidate critical interactions within the HCMV tegument, focusing on the phosphoproteins pp150, pp65, and pp71 (Aim 2). Finally, by AI-empowered cellular cryoET, we will define how uncoated HCMV particles with inner tegument proteins undergo microtubule-guided retrograde transport and dock at nuclear pore complexes to facilitate genome ejection into the nucleus (Aim 3). The expected results will elucidate the mechanisms of tegument protein-host interactions governing viral replication and inform efforts to develop anti-HCMV therapies.


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 = $450,254 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	7	5/14/2026	NON-COMPETING CONTINUATION	$450,254
														Subtotal = $450,254

Issue Date FY: 2025 ( Subtotal = $462,635 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	6	8/13/2025	COMPETING CONTINUATION	$462,635
2025	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	001	5	8/18/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $462,635

Issue Date FY: 2023 ( Subtotal = $471,864 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	5	3/23/2023	NON-COMPETING CONTINUATION	$471,864
														Subtotal = $471,864

Issue Date FY: 2022 ( Subtotal = $468,353 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	004	4	4/26/2022	NON-COMPETING CONTINUATION	-$119,513
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	002	4	4/22/2022	SUPPLEMENT FOR EXPANSION	$12,072
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	005	4	9/20/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	001	4	3/28/2022	SUPPLEMENT FOR EXPANSION	$108,649
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	003	4	4/25/2022	NON-COMPETING CONTINUATION	$151,117
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	4	3/24/2022	NON-COMPETING CONTINUATION	$316,028
														Subtotal = $468,353

Issue Date FY: 2021 ( Subtotal = $471,864 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	3	4/19/2021	NON-COMPETING CONTINUATION	$471,864
														Subtotal = $471,864

Issue Date FY: 2020 ( Subtotal = $471,864 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Oral Diseases and Disorders Research	001	2	4/17/2020	SUPPLEMENT FOR EXPANSION	$120,721
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	2	3/31/2020	NON-COMPETING CONTINUATION	$351,143
														Subtotal = $471,864

Issue Date FY: 2019 ( Subtotal = $364,443 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	1	2/15/2019	NEW	$364,443
														Subtotal = $364,443

Grand Total All Awards = $3,161,277

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Structural basis of human cytomegalovirus replication within host cells

Award Number: R01DE028583

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer