Kaposi Sarcoma

Human Herpesvirus 8-associated multicentric Castleman disease is predominantly observed in HIV-positive patients, but there is evidence of its occurrence in human immunodeficiency virus-negative individuals, presenting distinct epidemiological and pathological characteristics. Early and precise diagnosis is essential, as the disease can progress rapidly and may lead to severe or fatal outcomes.

By integrating locus-specific chromatin proteomics with functional and mechanistic analyses, our work reveals how an RNA-binding protein HNRNPA2B1 recruits a histone-modifying enzyme to control EBV reactivation. These findings provide new insights into host-virus interactions that control EBV latency and reactivation and highlight the role of RNA-binding proteins in chromatin regulation that may be broadly relevant to other latent DNA viruses.

Notably, the E3 ubiquitin ligase TRIM37 (tripartite motif containing 37) facilitates the polyubiquitination of lysine residues at position 116 of PFN1, which serves as a critical recognition motif for the cargo receptor SQSTM1/p62 (sequestosome 1), which is pivotal for the subsequent autophagic degradation of ORF44. Overall, our findings revealed a previously uncharacterized antiviral function of PFN1, highlighting its potential as a novel therapeutic avenue for the treatment of KSHV-associated malignancies.

Immediate ART initiation significantly reduces infection-related cancer risk in PWH that persists long-term.

The phenotype arises independently of viral DNA replication, indicating early host remodeling. A screen of EBV early genes identifies BRRF1 as a key driver: through a CIY(Y/E) motif conserved in KSHV ORF49, BRRF1 engages the nuclear CCR4-NOT complex through its CNOT9 and CNOT1 subunits, hijacking this canonically cytoplasmic deadenylation hub for nuclear disruption of host splicing.

KDR was found to promote lytic replication, stimulate the release of pro-inflammatory cytokines, and upregulate cancer signaling pathways. As such, we propose a model in which elevated KDR in KS lesions supports a lytic program to ensure maintenance and spread of infected cells while also promoting the tumor microenvironment.

Proteomic analysis identified unique protein candidates altered in MZ-1- and SIM-1-treated KSHV-infected immortalized endothelial cells compared with (+)-JQ1-treated cells. In summary, our study develops an effective strategy against KSHV-infected immortalized endothelial cells using selective BRD PROTACs, which may help improve therapeutic outcomes for KSHV-related malignancies in the future.

Among PWH with cancer, cancer-specific mortality increased with lower CD4 counts, including for solid tumors not associated with HIV, e.g., prostate and lung cancer. These results highlight the role of immunity in control of cancer.

Consistently, the responsiveness of LCLs to diABZI aligned with STING pathway competence, with minimal effects on growth and viability when STING expression was low or deficient. Overall, this work links STING pathway competence to both antiviral control of KSHV reactivation and reduced lymphoma growth, suggesting a potential new approach to limit KSHV pathogenesis.

spatiAlytica outperformed strong agentic baselines, while using less time and tokens. Case studies across Kaposi's sarcoma, colorectal cancer, and ovarian cancer recapitulated known spatial patterns and uncovered progressive CD8 T-cell dysfunction during KS progression.

Reanalysis of the enzymes that can modulate DNA methylation, a process that regulates L1 expression, revealed upregulation of DNMT3A and TET2 in both mouse KSHV tumor models and human KS. Altogether, our findings establish the L1 activation as a hallmark of KSHV-driven oncogenesis.

The development of nanoparticle delivery systems addresses critical limitations such as miRNA instability and ensures targeted delivery, representing a significant advance in therapeutic design. This review examines the multifaceted role of miRNAs in KS pathogenesis and explores innovative miRNA-based therapeutic interventions to combat this malignancy effectively.