Kaposi sarcoma (KS) is the most common HIV-associated malignancy worldwide and causes significant morbidity and mortality, particularly in sub-Saharan Africa. Human herpesvirus-8 (HHV-8) is the etiologic agent of KS, but the natural history of progression from asymptomatic HHV-8 infection to KS development is poorly understood. Viral genomic diversity plays an important role in the risk of cancer and response to treatment in some oncogenic viruses, but HHV-8 genomic heterogeneity has been described in only limited regions of the viral genome and the potential contribution of HHV-8 diversity to KS pathogenesis and treatment outcomes is unknown. The overarching goal of this project is to provide the first comprehensive description of HHV-8 genome diversity, at the individual and population level, and to evaluate the association of HHV-8 polymorphisms with disease state and therapeutic response. Using state-of-the-art molecular technologies, we propose to determine sequence diversity over the whole HHV-8 genome in specimens from well-annotated cohorts of HHV-8/HIV-1 co-infected persons with and without KS in Uganda.
In Aim 1, we will comprehensively characterize HHV-8 diversity to define common polymorphisms and phylogenetic groupings across the cohort population.
In Aim 2, we will perform single-genome sequence analysis of polymorphic HHV-8 regions in additional paired oral, plasma and tumor specimens within individuals to determine whether multiple viral variants coexist and whether there is compartmentalization of variants in different anatomic sites.
In Aim 3, we will explore associations of HHV-8 polymorphisms with KS disease state and treatment outcomes to identify polymorphisms with potential biologic significance, which may ultimately serve as predictive or treatment-selective biomarkers or targets of therapy.

Public Health Relevance

The proposed study will define HHV-8 genomic diversity and identify common polymorphisms in HHV-8/HIV-1 co-infected persons with and without KS. This effort will enable the discovery of potential predictive and treatment-selective biomarkers and novel therapeutic targets on HHV-8, and determine the impact of KS treatment on residual virus.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1-RPRB-O (M2))
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Dominguez, Geraldina
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Fred Hutchinson Cancer Research Center
United States
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Beima-Sofie, Kristin; Wamalwa, Dalton; Maleche-Obimbo, Elizabeth et al. (2018) Toll-like receptor 9 polymorphism is associated with increased Epstein-Barr virus and Cytomegalovirus acquisition in HIV-exposed infants. AIDS 32:267-270
Coghill, Anna E; Schenk, Jeannette M; Mahkoul, Zeina et al. (2018) Omega-3 decreases IL-6 levels in HIV and human herpesvirus-8 coinfected patients in Uganda. AIDS 32:505-512
Menon, Manoj P; Coghill, Anna; Mutyaba, Innocent O et al. (2018) Association Between HIV Infection and Cancer Stage at Presentation at the Uganda Cancer Institute. J Glob Oncol :1-9
Bender Ignacio, Rachel; Ghadrshenas, Matine; Low, Daniel et al. (2018) HIV Status and Associated Clinical Characteristics Among Adult Patients With Cancer at the Uganda Cancer Institute. J Glob Oncol :1-10
Phipps, Warren; Kansiime, Rachel; Stevenson, Philip et al. (2018) Peer Mentoring at the Uganda Cancer Institute: A Novel Model for Career Development of Clinician-Scientists in Resource-Limited Settings. J Glob Oncol :1-11
Coghill, Anna E; Schenk, Jeanette M; Mahkoul, Zeina et al. (2017) Omega-3 decreases interleukin-6 levels in HIV and HHV-8 co-infected patients: results from a randomized supplementation trial in Uganda. AIDS :
Okuku, Fred; Krantz, Elizabeth M; Kafeero, James et al. (2017) Evaluation of a Predictive Staging Model for HIV-Associated Kaposi Sarcoma in Uganda. J Acquir Immune Defic Syndr 74:548-554
Low, Daniel; Merkel, Emily C; Menon, Manoj et al. (2017) Chemotherapy Use at the End of Life in Uganda. J Glob Oncol 3:711-719
Casper, Corey; Fitzmaurice, Christina (2016) Infection-related cancers: prioritising an important and eliminable contributor to the global cancer burden. Lancet Glob Health 4:e580-1