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Genetic Pathways of Human Cytomegalovirus Drug Resistance

Award Number: R01AI116635
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: 08/01/2015
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Genetic Pathways of Human Cytomegalovirus Drug Resistance - Project Summary Toxicity and drug resistance limit the efficacy of antiviral therapy for cytomegalovirus (CMV) disease in immunosuppressed hosts such as cancer and transplant recipients. Current therapy includes DNA polymerase inhibitors ganciclovir, foscarnet and cidofovir. The terminase inhibitor letermovir was recently approved for prophylaxis, and the UL97 kinase inhibitor maribavir has completed Phase 3 trial as alternative therapy. In clinical practice, CMV drug resistance cannot be diagnosed by direct phenotypic testing of viral isolates, and instead is dependent on an accurate correlation of detected viral mutations and associated resistance phenotypes. The objective of this research is to determine the genetic mechanisms of CMV drug resistance in order to improve clinical diagnosis and the development of new antivirals. Many resistance mutations and polymorphisms in the CMV UL97 kinase, UL54 DNA polymerase and UL56/UL89/UL51 terminase genes have been and continue to be phenotyped, with diagnostically important new resistance loci being identified during each project period. Technical advances in recombinant phenotyping and whole genome deep sequencing are facilitating this research. In the upcoming project period, new focus areas include the characterization of mutations selected after drug exposure in genes outside of known antiviral targets, and analysis of the effects of baseline viral strain variation on drug susceptibility. Specific aims are (1) study the evolution and phenotypes of CMV mutations that develop after in vitro or in vivo exposure to antiviral compounds and combinations; (2) evaluate the phenotypic significance of genetic changes identified by viral whole genome deep sequencing that are outside of known antiviral target genes, and (3) determine the impact of baseline viral strain on drug susceptibility phenotypes by characterization of alternative viral clones and host cells.


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 = $312,000 )
2025	2025	PORTLAND VA RESEARCH FOUNDATION, INC.	3710 SW US VETERANS HOSPITAL RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	9	3/10/2025	NON-COMPETING CONTINUATION	$312,000
														Subtotal = $312,000

Issue Date FY: 2024 ( Subtotal = $312,000 )
2024	2024	PORTLAND VA RESEARCH FOUNDATION, INC.	3710 SW US VETERANS HOSPITAL RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	002	8	7/16/2024	NON-COMPETING CONTINUATION	$31,200
2024	2024	PORTLAND VA RESEARCH FOUNDATION, INC.	3710 SW US VETERANS HOSPITAL RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	003	8	9/5/2024	NON-COMPETING CONTINUATION	$0
2024	2024	PORTLAND VA RESEARCH FOUNDATION, INC.	3710 SW US VETERANS HOSPITAL RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	8	2/1/2024	NON-COMPETING CONTINUATION	$280,800
2024	2024	PORTLAND VA RESEARCH FOUNDATION, INC.	3710 SW US VETERANS HOSPITAL RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	001	8	4/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $312,000

Issue Date FY: 2023 ( Subtotal = $692,328 )
2023	2023	PORTLAND VA RESEARCH FOUNDATION, INC	3710 SW US VETERANS HOSPITAL RD G218	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	7	1/20/2023	NON-COMPETING CONTINUATION	$312,000
2023	2022	PORTLAND VA RESEARCH FOUNDATION, INC.	3710 SW US VETERANS HOSPITAL RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	001	6	3/6/2023	COMPETING CONTINUATION	$380,328
														Subtotal = $692,328

Issue Date FY: 2022 ( Subtotal = $59,635 )
2022	2022	PORTLAND VA RESEARCH FOUNDATION, INC	3710 SW US VETERANS HOSPITAL RD G218	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	6	1/28/2022	COMPETING CONTINUATION	$130,000
2022	2019	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	001	5	4/22/2022	NON-COMPETING CONTINUATION	-$70,365
														Subtotal = $59,635

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	5	1/13/2021	NON-COMPETING CONTINUATION	$0
2021	2019	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	001	5	8/19/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $315,000 )
2019	2019	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	5	12/21/2018	NON-COMPETING CONTINUATION	$315,000
														Subtotal = $315,000

Issue Date FY: 2018 ( Subtotal = $315,000 )
2018	2018	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	4	1/25/2018	NON-COMPETING CONTINUATION	$315,000
														Subtotal = $315,000

Issue Date FY: 2017 ( Subtotal = $315,000 )
2017	2017	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	3	1/31/2017	NON-COMPETING CONTINUATION	$315,000
														Subtotal = $315,000

Issue Date FY: 2016 ( Subtotal = $315,000 )
2016	2016	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	2	1/13/2016	NON-COMPETING CONTINUATION	$315,000
														Subtotal = $315,000

Issue Date FY: 2015 ( Subtotal = $157,500 )
2015	2015	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	1	7/23/2015	NEW	$157,500
														Subtotal = $157,500

Grand Total All Awards = $2,793,463

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Genetic Pathways of Human Cytomegalovirus Drug Resistance

Award Number: R01AI116635

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: 08/01/2015

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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