Whole-genome sequencing of Kaposi sarcoma-associated herpesvirus (KSHV/HHV8) reveals evidence for two African lineages

Moorad, Razia; Juarez, Angelica; Landis, Justin T.; Pluta, Linda; Perkins, Megan; Cheves, Avery; Dittmer, Dirk P.

doi:10.1016/j.virol.2022.01.005

Cited by 9 publications

(10 citation statements)

References 86 publications

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“…This assured us that there was no contamination across samples. This is consistent with other studies documenting similar population variance of KSHV in KS endemic regions ( 37 – 39 ).…”

Section: Resultssupporting

confidence: 93%

Pediatric HIV+ Kaposi sarcoma exhibits clinical, virological, and molecular features different from the adult disease

Caro-Vegas,

Peng,

Juarez

et al. 2023

JCI Insight

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BACKGROUND Kaposi sarcoma (KS) is among the most common childhood cancers in Eastern and Central Africa. Pediatric KS has a distinctive clinical presentation compared with adult KS, which includes a tendency for primary lymph node involvement, a considerable proportion of patients lacking cutaneous lesions, and a potential for fulminant disease. The molecular mechanisms or correlates for these disease features are unknown. METHODS This was a cross-sectional study. All cases were confirmed by IHC for KS-associated herpesvirus (KSHV) LANA protein. Baseline blood samples were profiled for HIV and KSHV genome copy numbers by qPCR and secreted cytokines by ELISA. Biopsies were characterized for viral and human transcription, and KSHV genomes were determined when possible. RESULTS Seventy participants with pediatric KS were enrolled between June 2013 and August 2019 in Malawi and compared with adult patients with KS. They exhibited high KSHV genome copy numbers and IL-6/IL-10 levels. Four biopsies (16%) had a viral transcription pattern consistent with lytic viral replication. CONCLUSION The unique features of pediatric KS may contribute to the specific clinical manifestations and may direct future treatment options. FUNDING US National Institutes of Health U54-CA-254569, PO1-CA019014, U54-CA254564, RO1-CA23958.

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“…This assured us that there was no contamination across samples. This is consistent with other studies documenting similar population variance of KSHV in KS endemic regions ( 37 – 39 ).…”

Section: Resultssupporting

confidence: 93%

Pediatric HIV+ Kaposi sarcoma exhibits clinical, virological, and molecular features different from the adult disease

Caro-Vegas,

Peng,

Juarez

et al. 2023

JCI Insight

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“…The variability of oncogenic and pathogenic KSHV potential was indicated to be dependent on KSHV different subtypes [ 42 ]. Overall, discovering distinct viral strains will adjust the different adopted approaches to tumor diagnosis, prognosis, prevention, advanced treatment, as well as therapy monitoring and will enrich potential vaccine studies [ 21 , 26 , 49 ]. Likewise, the diversity of HCMV strains was validated by our data and the previously published data in which only few clinical HCMV strains conserve the potential to transform HMECs [ 6 ] and fit with a “blastomere-like” model of oncogenesis [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

“…Various Epstein–Barr virus (EBV) strains are associated with properties that influence their transforming capacities and the type of induced tumor [ 22 , 23 ]. Additionally, Kaposi’s sarcoma-associated herpesvirus (KSHV) isolates were identified in patients of different geographical regions, indicating the importance of these newly isolated strains [ 24 , 25 ] in developing better diagnostic procedures and novel treatment approaches in the context of KSHV-associated malignancies as well as enriching potential vaccine studies [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Oncogenic and Stemness Signatures of the High-Risk HCMV Strains in Breast Cancer Progression

Baba

Pasquereau

Ahmad

et al. 2022

Cancers

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Background: Human cytomegalovirus (HCMV) oncomodulation, molecular mechanisms, and ability to support polyploid giant cancer cells (PGCCs) generation might underscore its contribution to oncogenesis, especially breast cancers. The heterogeneity of strains can be linked to distinct properties influencing the virus-transforming potential, cancer types induced, and patient’s clinical outcomes. Methods: We evaluated the transforming potential in vitro and assessed the acquired cellular phenotype, genetic and molecular features, and stimulation of stemness of HCMV strains, B544 and B693, isolated from EZH2HighMycHigh triple-negative breast cancer (TNBC) biopsies. Therapeutic response assessment after paclitaxel (PTX) and ganciclovir (GCV) treatment was conducted in addition to the molecular characterization of the tumor microenvironment (TME). Findings: HCMV-B544 and B693 transformed human mammary epithelial cells (HMECs). We detected multinucleated and lipid droplet-filled PGCCs harboring HCMV. Colony formation was detected and Myc was overexpressed in CMV-Transformed-HMECs (CTH cells). CTH-B544 and B693 stimulated stemness and established an epithelial/mesenchymal hybrid state. HCMV-IE1 was detected in CTH long-term cultures indicating a sustained viral replication. Biopsy B693 unveiled a tumor signature predicting a poor prognosis. CTH-B544 cells were shown to be more sensitive to PTX/GCV therapy. Conclusion: The oncogenic and stemness signatures of HCMV strains accentuate the oncogenic potential of HCMV in breast cancer progression thereby leading the way for targeted therapies and innovative clinical interventions that will improve the overall survival of breast cancer patients.

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“…Human herpesvirus-8 or Kaposi sarcoma-associated herpesvirus HHV-8 genomic organization and protein products HHV-8 is a double-stranded DNA virus of approximately 140 kilobases. Its genome is structured like other herpesviruses, with a single long unique region flanked by GC-rich terminal repeats at both the 3' and 5' ends (314). While the central region of the genome is highly conserved, both ends demonstrate significant variability.…”

Section: Future Directionsmentioning

confidence: 99%

Malignancy and viral infections in Sub-Saharan Africa: A review

Diakité

Shaw‐Saliba²,

Lau³

2023

Front. Virol.

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The burden of malignancy related to viral infection is increasing in Sub-Saharan Africa (SSA). In 2018, approximately 2 million new cancer cases worldwide were attributable to infection. Prevention or treatment of these infections could reduce cancer cases by 23% in less developed regions and about 7% in developed regions. Contemporaneous increases in longevity and changes in lifestyle have contributed to the cancer burden in SSA. African hospitals are reporting more cases of cancer related to infection (e.g., cervical cancer in women and stomach and liver cancer in men). SSA populations also have elevated underlying prevalence of viral infections compared to other regions. Of 10 infectious agents identified as carcinogenic by the International Agency for Research on Cancer, six are viruses: hepatitis B and C viruses (HBV and HCV, respectively), Epstein-Barr virus (EBV), high-risk types of human papillomavirus (HPV), Human T-cell lymphotropic virus type 1 (HTLV-1), and Kaposi’s sarcoma herpesvirus (KSHV, also known as human herpesvirus type 8, HHV-8). Human immunodeficiency virus type 1 (HIV) also facilitates oncogenesis. EBV is associated with lymphomas and nasopharyngeal carcinoma; HBV and HCV are associated with hepatocellular carcinoma; KSHV causes Kaposi’s sarcoma; HTLV-1 causes T-cell leukemia and lymphoma; HPV causes carcinoma of the oropharynx and anogenital squamous cell cancer. HIV-1, for which SSA has the greatest global burden, has been linked to increasing risk of malignancy through immunologic dysregulation and clonal hematopoiesis. Public health approaches to prevent infection, such as vaccination, safer injection techniques, screening of blood products, antimicrobial treatments and safer sexual practices could reduce the burden of cancer in Africa. In SSA, inequalities in access to cancer screening and treatment are exacerbated by the perception of cancer as taboo. National level cancer registries, new screening strategies for detection of viral infection and public health messaging should be prioritized in SSA’s battle against malignancy. In this review, we discuss the impact of carcinogenic viruses in SSA with a focus on regional epidemiology.

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Whole-genome sequencing of Kaposi sarcoma-associated herpesvirus (KSHV/HHV8) reveals evidence for two African lineages

Cited by 9 publications

References 86 publications

Pediatric HIV+ Kaposi sarcoma exhibits clinical, virological, and molecular features different from the adult disease

Pediatric HIV+ Kaposi sarcoma exhibits clinical, virological, and molecular features different from the adult disease

Oncogenic and Stemness Signatures of the High-Risk HCMV Strains in Breast Cancer Progression

Malignancy and viral infections in Sub-Saharan Africa: A review

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