Human Herpesviruses: Kaposi’s Sarcoma and Other Malignancies

Sarid, Ronit; Dünn-Kittenplon, Daniela; Calabrò, Maria Luisa

doi:10.1007/978-1-4939-9544-8_39-1

Cited by 1 publication

(1 citation statement)

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“…The prevalence of KSHV infection varies greatly, with <10% in most parts of Europe, the United States, and Asia, as opposed to over 90% in some countries of sub‐Saharan Africa 1,2 . In Israel, the seroprevalence of KSHV is estimated to be <10% in the majority of the population, with the exception of relatively high prevalence in people of Ethiopian descent, 3 yet the overall incidence of KS has declined over the years 4 . KSHV infection is necessary, yet not sufficient, for KS development.…”

Section: Introductionmentioning

confidence: 99%

A role of BPTF in viral oncogenicity delineated through studies of heritable Kaposi sarcoma

Yogev,

Schaffer,

Shlapobersky

et al. 2024

Journal of Medical Virology

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Kaposi sarcoma (KS), caused by Herpesvirus‐8 (HHV‐8; KSHV), shows sporadic, endemic, and epidemic forms. While familial clustering of KS was previously recorded, the molecular basis of hereditary predilection to KS remains largely unknown. We demonstrate through genetic studies that a dominantly inherited missense mutation in BPTF segregates with a phenotype of classical KS in multiple immunocompetent individuals in two families. Using an rKSHV.219‐infected CRISPR/cas9‐model, we show that BPTFI2012T mutant cells exhibit higher latent‐to‐lytic ratio, decreased virion production, increased LANA staining, and latent phenotype in viral transcriptomics. RNA‐sequencing demonstrated that KSHV infection dysregulated oncogenic‐like response and P53 pathways, MAPK cascade, and blood vessel development pathways, consistent with KS. BPTFI2012T also enriched pathways of viral genome regulation and replication, immune response, and chemotaxis, including downregulation of IFI16, SHFL HLAs, TGFB1, and HSPA5, all previously associated with KSHV infection and tumorigenesis. Many of the differentially expressed genes are regulated by Rel‐NF‐κB, which regulates immune processes, cell survival, and proliferation and is pivotal to oncogenesis. We thus demonstrate BPTF mutation‐mediated monogenic hereditary predilection of KSHV virus‐induced oncogenesis, and suggest BPTF as a drug target.

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Section: Introductionmentioning

confidence: 99%