The Viral Oncology Section studies the epidemiology, immune response, and genetics of Kaposi sarcoma–associated herpesvirus (KSHV). Our work extends to related oncogenic viruses and associated malignancies.

Understanding the role of viruses in cancer 

Seven viruses are known to cause about 20% of human cancers. Our studies are primarily focused on KSHV (also called human herpesvirus 8 or HHV8). Infection with KSHV causes Kaposi sarcoma and less common lymphoproliferative diseases. KSHV-related diseases occur frequently among inhabitants of certain areas of sub-Saharan Africa where malaria is common, and worldwide in people living with HIV, as well as in other immunocompromised individuals.  

From the field to the laboratory to the bedside 

Our approach to research encompasses a range of disciplines, starting with epidemiology and clinical virology, which informs the study of basic biological processes in immunology, genetics, and cellular and molecular biology. Through the multidirectional integration of basic and applied research studies, we aim to improve understanding about KSHV infection and associated diseases, with the goal of advancing the prevention and management of risks associated with KSHV infection.  

To achieve our research goals, we developed an extensive network of collaborations with investigators at the National Cancer Institute and extramural partners throughout the United States, Uganda, Cameroon, Kenya, South Africa, and worldwide. 

Collaboration Opportunities

AIDS and Cancer Virus Program research sections and research support cores collaborate with scientists within and outside the National Institutes of Health to address key remaining challenges in the prevention and treatment of HIV infection and associated conditions. We engage with external investigators through partnership mechanisms, including Cooperative Research and Development Agreements (CRADAs), Material Transfer Agreements (MTAs), Technical Service Agreements (TSAs).

Southern U.S. is new KSHV frontier

In the South, KSHV is severely affecting men who have sex with men with HIV

High seroprevalence of KSHV in Texas drives an elevated burden of KSHV-associated diseases.
Sensitive and specific testing

KSHV viral load in CSF is a biomarker for primary effusion lymphoma

Largest study of cerebrospinal fluid involvement in patients with KSHV-associated PEL.

Our capabilities and specializations

Analysis of KSHV immunity  

We developed a systematic multiplexed bead-based assay to detect IgG, IgM, and IgA against KSHV, from a select few antigens to the entire KSHV proteome. Furthermore, KSHV-specific T-cell responses encompassing 86 known KSHV proteins can be assessed. 

  • Detection of anti-KSHV antibodies

  • Multiplexed bead-based assays

  • Detection of KSHV-specific T-cell responses using interferon-γ ELISpot assays 

Detection and characterization of KSHV  

Our KSHV viral load assays are utilized in blood, saliva, and other relevant tissues and compartments to estimate viral replication, for example, to measure virological endpoints in clinical trials.  

  • Quantitation of KSHV DNA via quantitative PCR (qPCR) 

Gene- or genome-level KSHV characterization 

Using different sequencing approaches, KSHV infection can be characterized on a gene or genome level. This allows us to characterize the molecular epidemiology of infection, including recently described multiple infections and recombination. 

  • KSHV genotyping

  • KSHV genome sequencing 

Cells containing rhesus retroperitoneal fibromatosis-associated herpesvirus (RFHV; a homolog to KSHV) viral DNA were primarily detected in lymphoid tissues, within B cell follicles, T cell areas and epithelium. RFHV viral DNA+ cells were also found within sub-capsular areas and connective tissues around lymphoid tissue. Representative images of DNAscope chromogenic approach; left panel: viral DNA in red; center and right panels: multiplex DNAscope + immunofluorescence to phenotype cell harboring DNA.
KSHV-specific T-cell responses

Diverse T-cell responses to KSHV may contribute to viral control

KSHV-specific T-cell responses in healthy people from high-risk populations may inhibit viral replication as individuals without detectable KSHV-specific T-cell responses have higher KSHV viral load.
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What is this? Cells containing rhesus retroperitoneal fibromatosis-associated herpesvirus (RFHV; a homolog to KSHV) viral DNA were primarily detected in lymphoid tissues, within B cell follicles, T cell areas and epithelium. RFHV viral DNA+ cells were also found within sub-capsular areas and connective tissues around lymphoid tissue. Representative images of DNAscope chromogenic approach; multiplex DNAscope + immunofluorescence to phenotype cell harboring DNA.
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Detailed mapping of the positions of single nucleotide variations, insertions and deletions (B ring) as well as linkage disequilibrium analysis (C ring) in the KSHV sequences analyzed from HIV+ participants.
KSHV genome sequencing

Viral genomics of KSHV from KS patients and controls to identify disease risk

We sequenced KSHV genomes from 43 Cameroonian people in a KS case-control study, observing polymorphisms across the entire genome and identifying multiple infections in several individuals. However, we did not find associations between viral sequence variations and disease risk. 
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What is this? Detailed mapping of the positions of single nucleotide variations, insertions and deletions (B ring) as well as linkage disequilibrium analysis (C ring) in the KSHV sequences analyzed from HIV+ participants. Masked repeat regions indicated in red. Graphs created with Circosplot.
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