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Defining the role of plasma cells in the establishment of KSHV infection in human tonsil

Award Number: R01CA264913
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Defining the role of plasma cells in the establishment of KSHV infection in human tonsil - Abstract/Project Summary Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic human herpesvirus, which causes Kaposi sarcoma (KS) as well as B cell lymphoproliferative disorders in the absence of adequate immune control. KSHV- associated tumors are a significant cause of morbidity and mortality in transplant patients and individuals with HIV- disease. The oral cavity is an important site for KSHV biology because saliva is believed to be the primary mode of person-to-person transmission for the virus. The tonsil and other oral lymphoid tissues represent a logical anatomical site for early infection events because they are in contact with saliva and are rich in target cell types for KSHV infection including endothelial cells and B lymphocytes. Despite this, the biology of KSHV in the human tonsil remains poorly understood. We have developed an extensive library of human tonsil specimens and a robust ex vivo infection model KSHV in tonsil-derived lymphocytes. Using these tools, we have recently discovered that mature plasma cells are highly targeted early in KSHV infection and that KSHV-infected plasma cells display a mixture of latent and lytic infection cycles. The current proposal will test several hypotheses: (1) plasma cell infection serves as an amplification step which is important for the overall establishment of infection in tonsil lymphocytes, (2) the KSHV-encoded cytokine vIL-6 is critical for establishment of KSHV infection in lymphocytes via manipulation of plasma cell biology and (3) the T cell-derived cellular cytokine IL-21 supports KSHV dissemination by driving differentiation of plasma cells, and can partially replace the function of vIL-6 in early infection. The results of this research will provide critical mechanistic details that will enhance our understanding of early events in KSHV transmission and the establishment of KSHV infection in the lymphocyte compartment.


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: 2024 ( Subtotal = $104,855 )
2024	2024	CHAPMAN UNIVERSITY	1 UNIVERSITY DR	ORANGE	CA	92866	ORANGE	USA	Cancer Biology Research	000	4	8/27/2024	NON-COMPETING CONTINUATION	$104,855
														Subtotal = $104,855

Issue Date FY: 2023 ( Subtotal = $345,000 )
2023	2023	CHAPMAN UNIVERSITY	1 UNIVERSITY DR	ORANGE	CA	92866	ORANGE	USA	Cancer Biology Research	000	3	8/18/2023	NON-COMPETING CONTINUATION	$345,000
														Subtotal = $345,000

Issue Date FY: 2022 ( Subtotal = $345,000 )
2022	2022	CHAPMAN UNIVERSITY	1 UNIVERSITY DR	ORANGE	CA	92866	ORANGE	USA	Cancer Biology Research	000	2	8/14/2022	NON-COMPETING CONTINUATION	$345,000
														Subtotal = $345,000

Issue Date FY: 2021 ( Subtotal = $341,200 )
2021	2021	CHAPMAN UNIVERSITY	ONE UNIVERSITY DR	ORANGE	CA	92866	ORANGE	USA	Cancer Biology Research	000	1	9/20/2021	NEW	$341,200
														Subtotal = $341,200

Grand Total All Awards = $1,136,055

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Defining the role of plasma cells in the establishment of KSHV infection in human tonsil

Award Number: R01CA264913

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/20/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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