^
6d
Associations between salivary microbiota and KSHV infection in people with HIV: a cross-sectional study in ili prefecture, Xinjiang, China. (PubMed, AIDS)
This study suggests the potential role of salivary microbiota in KSHV transmission among PWH. Identified microbial genera offer promising biomarkers for monitoring and managing KSHV in PWH.
Observational data • Journal
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
6d
Senescence of endothelial cells increases susceptibility to Kaposi's sarcoma-associated herpesvirus infection via CD109-mediated viral entry. (PubMed, J Clin Invest)
Furthermore, surface plasmon resonance analysis and confocal microscopy revealed a direct interaction between KSHV virions and CD109 on the cell surface during entry, with recombinant CD109 protein exhibiting an intriguing ability to inhibit infection by blocking virion binding. These findings uncover a previously unrecognized role of cellular senescence in enhancing KSHV infection through upregulation of specific host factors and provide novel insights into the complex interplay between aging and viral pathogenesis.
Journal
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CAV1 (Caveolin 1)
8d
A KSHV RNA-binding protein promotes FOS to inhibit nuclease AEN and transactivate RGS2 for AKT phosphorylation. (PubMed, mBio)
FOS inhibits AEN transcription by binding to the AEN promoter but transactivates RGS2 by binding to a conserved AP-1 site in the RGS2 promoter, thereby enhancing RGS2 expression and phosphorylation of AKT. Thus, KSHV lytic infection controls the expression of a subset of genes for signaling, cell cycle progression, and proliferation to potentially contribute to viral oncogenesis.
Journal
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RGS2 (Regulator Of G Protein Signaling 2)
8d
A KSHV-targeted Small Molecule Efficiently Blocks SARS-CoV-2 Infection via Inhibiting Expression of EGFR and Cyclin A2. (PubMed, Emerg Microbes Infect)
Importantly, Cambogin not only efficiently blocks the replication and virion production of SARS-CoV-2 in vitro and in vivo by reducing the expression of EGFR and Cyclin A2, but also simultaneously inhibits both SARS-CoV-2 infection and the growth of KSHV-induced tumors in vivo using a murine xenograft model. These findings provide an alternative strategy for the potential use of Cambogin in the treatment of SARS-CoV-2 patients, particularly those with KSHV co-infection.
Journal
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EGFR (Epidermal growth factor receptor) • CCNA2 (Cyclin A2)
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EGFR expression
10d
Kaposi Sarcoma Chemotherapy and Research (KS-CARE) (clinicaltrials.gov)
P=N/A, N=180, Recruiting, UNC Lineberger Comprehensive Cancer Center | Not yet recruiting --> Recruiting | N=90 --> 180 | Trial completion date: Jun 2026 --> Jun 2027 | Initiation date: Dec 2024 --> Apr 2023 | Trial primary completion date: Jun 2025 --> Jun 2027
Enrollment open • Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date
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paclitaxel
10d
B-Lymphoblastic Leukemia with BCR::ABL1-like Features After Long-term Lenalidomide Therapy. (PubMed, J Assoc Genet Technol)
Lenalidomide, a derivative of thalidomide, is a type of immunomodulatory drug (IMiD) that has been standard therapy for multiple myeloma (MM) and other hematologic malignancies for almost two decades. In addition, treatment with IMiDs is also associated with an increased risk for myelodysplastic neoplasms (MDS), squamous cell carcinoma of the skin, and, less frequently, acute lymphoblastic leukemia (ALL). We present a case of an elderly male with MM and multiple subsequent skin cancers, who presented with pancytopenia and was diagnosed with B-lymphoblastic leukemia (B-ALL) after 10 years of maintenance lenalidomide therapy.
Journal
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ABL1 (ABL proto-oncogene 1)
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lenalidomide • thalidomide
14d
Facing Clostridioides difficile infection in a resource - Limiting setting. (PubMed, Rev Esp Enferm Dig)
An HIV- positive patient with Kaposi's sarcoma and undergoing chemotherapy, had been on antibiotic therapy for around 14 days with ceftriaxone and imipenem. Oral vancomycin is the treatment of choice, however it was not available in the hospital, so treatment with oral metronidazole was made and the previous antibiotics used were discontinued. The patient progressed with clinical improvement.
Journal
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CD4 (CD4 Molecule)
20d
Hsp70-Hsp90 organising protein (HOP/STIP1) is required for KSHV lytic replication. (PubMed, J Gen Virol)
While the roles for Hsp90 and Hsp70 in KSHV biology have been described, HOP has not previously been studied in this context despite its prominent interaction with both chaperones. Here, we demonstrate a novel function for HOP as a new host factor required for effective lytic replication of KSHV in primary effusion cell lines.
Journal
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HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
22d
Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability. (PubMed, Nat Commun)
We highlight these virus-modified paraspeckles form adjacent to virus replication centres, potentially functioning as RNA processing hubs for viral transcripts during infection. Notably, we reveal that PSP sequestration into virus-modified paraspeckles result in increased genome instability during both KSHV and Epstein Barr virus (EBV) infection, implicating their formation in virus-mediated tumourigenesis.
Journal
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NEAT1 (Nuclear Paraspeckle Assembly Transcript 1)
22d
Retargeting target-directed microRNA-decay sites to highly expressed viral or cellular miRNAs. (PubMed, Nucleic Acids Res)
Surprisingly, inactivation of ZSWIM8, a key mediator of TDMD, did not substantially affect miRNA inhibition by retargeted Cyrano-based inhibitors in 293T or PEL cells. Together, our results demonstrate the feasibility of retargeting natural TDMD sites to highly expressed viral or cellular miRNAs and further define features of effective encoded miRNA inhibitors.
Journal
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MIR155 (MicroRNA 155)
27d
Clinical, demographic and histopathological characteristics of individuals with Kaposi's sarcoma and living with HIV in Mexico (PubMed, Rev Med Inst Mex Seguro Soc)
Our study highlights the need for an early and multidisciplinary approach in the management of KS in HIV-positive patients, underlining the importance of antiretroviral treatment to prevent disease progression. Furthermore, it stresses its complexity and the significant prevalence of opportunistic infections, advocating for comprehensive strategies addressing sarcoma as well as concomitant infections.
Observational data • Retrospective data • Journal
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CD4 (CD4 Molecule)
27d
Early Mortality and Health Care Costs in Patients Recently Diagnosed With Kaposi Sarcoma at the National Cancer Institute, Mexico City. (PubMed, Open Forum Infect Dis)
The total care cost was US $183 947.48, equivalent to a screening program in key populations, which would have allowed the early detection of 1227 cases and saved 8410 disability-adjusted life years. Reinforcement of early HIV infection detection in key population programs should be prioritized to reduce KS-associated deaths and YLL and for rational use of health budgets.
Journal • HEOR
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
1m
Exploring the mechanism of action of Modified Simiao Powder in the treatment of osteoarthritis: an in-silico study. (PubMed, Front Med (Lausanne))
The therapeutic effect of MSMP likely attributed to the modulation of multiple pathways, including lipid metabolism, atherosclerosis, the AGE-RAGE signaling pathway, and the PI3K-Akt signaling pathway, by the active components such as berberine, kaempferol, luteolin, and quercetin. Especially, their actions on target genes like AR and AKT1 contribute to the therapeutic benefits of MSMP observed in the treatment of OA.
Journal
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AR (Androgen receptor) • MAPK1 (Mitogen-activated protein kinase 1) • CASP3 (Caspase 3)
2ms
A LANA peptide inhibits tumor growth by inducing CHD4 protein cleavage and triggers cell death. (PubMed, Cell Chem Biol)
Furthermore, the introduction of the peptide into the cancer cells induced caspase-mediated CHD4 cleavage, triggered cell death, and inhibited tumor growth in a xenograft mouse model. The VGN73 may facilitate cell differentiation therapy.
Journal
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CHD4 (Chromodomain Helicase DNA Binding Protein 4)
2ms
Engineered protein destabilization reverses intrinsic immune evasion for candidate vaccine pan-strain KSHV and SARS-CoV-2 antigens. (PubMed, bioRxiv)
These mice developed robust T cell responses lasting at least 90 days post-injection that recognized native viral protein epitopes. Engineered vaccine candidate antigens can unmask virus-specific CTL responses that are typically suppressed during native viral infection.
Journal
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CD8 (cluster of differentiation 8)
2ms
Modulators of the Hop-HSP90 Protein-Protein Interaction Disrupt KSHV Lytic Replication. (PubMed, ACS Infect Dis)
The inhibitory peptides selectively engaged the HopTPR2A domain in cell lysates and when tethered to a cell-penetrating peptide acted as noncytotoxic inhibitors of KSHV lytic replication by lowering the viral load, preventing the production of infectious virions, and reducing the expression of KSHV lytic genes. In addition to tentative evidence of Hop-HSP90 PPI as a much-needed target for KSHV drug discovery, this study represents an important step in understanding viral interactions with the host proteostasis machinery.
Journal
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HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
2ms
BiP/GRP78 is a pro-viral factor for diverse dsDNA viruses that promotes the survival and proliferation of cells upon KSHV infection. (PubMed, PLoS Pathog)
Notably, inhibition of BiP limits the spread of other alpha- and beta-herpesviruses and poxviruses with minimal toxicity for normal cells. Our work suggests that BiP is a potential target for developing broad-spectrum antiviral therapies against double-stranded DNA viruses and a promising candidate for therapeutic intervention in KSHV-related malignancies.
Journal
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HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5)
2ms
Transcriptome analysis of the cytokine storm-related genes among the subtypes of idiopathic multicentric Castleman disease. (PubMed, J Clin Exp Hematop)
Particularly, upregulated IL33 expression was demonstrated for the first time in iMCD-TAFRO/NOS. Thus, inflammatory signaling, such as JAK-STAT and MAPK, may be enhanced in iMCD-TAFRO/NOS and may be a cytokine storm.
Journal
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JAK2 (Janus kinase 2) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • JAK1 (Janus Kinase 1) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • MAPK1 (Mitogen-activated protein kinase 1) • VEGFC (Vascular Endothelial Growth Factor C) • IL17A (Interleukin 17A) • IL17RA (Interleukin 17 Receptor A) • PDGFA (Platelet Derived Growth Factor Subunit A) • PDGFB (Platelet Derived Growth Factor Subunit B) • STAT1 (Signal Transducer And Activator Of Transcription 1) • STAT6 (Signal transducer and activator of transcription 6) • IL18BP (Interleukin 18 Binding Protein) • IL1R1 (Interleukin 1 receptor, type I) • IL1RAP (Interleukin 1 Receptor Accessory Protein) • NFKBIA (NFKB Inhibitor Alpha 2) • STAT2 (Signal transducer and activator of transcription 2) • IL3 (Interleukin 3) • IL33 (Interleukin 33) • MAPK11 (Mitogen-Activated Protein Kinase 11) • MAPK12 (Mitogen-Activated Protein Kinase 12) • MAPK14 (Mitogen-Activated Protein Kinase 14) • MAPK3 (Mitogen-Activated Protein Kinase 3) • MAPK8 (Mitogen-activated protein kinase 8) • MAPK9 (Mitogen-Activated Protein Kinase 9) • PDGFC (Platelet Derived Growth Factor C) • TNFAIP8 (TNF Alpha Induced Protein 8) • MAPK10 (Mitogen-Activated Protein Kinase 10)
2ms
New P2 trial
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Keytruda (pembrolizumab)
2ms
Insight into structural properties of viral G protein-coupled receptors and their role in the viral infection: IUPHAR Review 41. (PubMed, Br J Pharmacol)
Open reading frame 74 (ORF74; Kaposi's sarcoma-associated herpesvirus) is compared to CXCRs, whereas BILF1 (Epstein-Barr virus) is discussed as a putative lipid receptor. Furthermore, the roles of vGPCRs in latency and lytic replication, reactivation, dissemination and immune evasion are reviewed, together with their potential as drug targets for virus infections and virus-related diseases.
Review • Journal
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CX3CR1 (C-X3-C Motif Chemokine Receptor 1)
2ms
On Vascular Lesions of the Thyroid Gland with Emphasis on Intrathyroidal Hemangioma: Clinicopathologic Characterization of Two Cases and Review of the Literature. (PubMed, Head Neck Pathol)
Prognosis is favorable and surgical resection is considered curative. The occasionally alarming clinical presentation in conjunction with absence of pathognomonic imaging features and limited diagnostic accuracy of FNA cytopathology for such lesions renders surgical intervention necessary for definitive diagnosis of intrathyroidal hemangiomas and exclusion of other epithelial and non-epithelial pathologic entities.
Review • Journal
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CD34 (CD34 molecule) • NKX2-1 (NK2 Homeobox 1) • CD31 (Platelet and endothelial cell adhesion molecule 1) • PAX8 (Paired box 8) • PECAM1 (Platelet And Endothelial Cell Adhesion Molecule 1)
2ms
Classic Kaposi sarcoma: Diagnostics, treatment modalities, and genetic implications - A review of the literature. (PubMed, Acta Oncol)
While advancements in CKS treatment offer hope, further studies on immunotherapy are warranted to broaden the therapeutic options, such as anti-bromodomain or BPTF-targeted therapy.
Review • Journal • IO biomarker
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MDM2 (E3 ubiquitin protein ligase) • BPTF (Bromodomain PHD Finger Transcription Factor)
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Verzenio (abemaciclib)
2ms
Lactylation of RNA m6A demethylase ALKBH5 promotes innate immune response to DNA herpesviruses and mpox virus. (PubMed, Proc Natl Acad Sci U S A)
Our results identify a posttranslational modification of ALKBH5 and its role in regulating antiviral innate immune responses through m6A modification. The finding provides an understanding of innate immunity and offers a potential therapeutic target for HSV-1, KSHV, and MPXV infections.
Journal
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SIRT6 (Sirtuin 6) • ALKBH5 (AlkB Homolog 5, RNA Demethylase) • ESCO2 (Establishment Of Sister Chromatid Cohesion N-Acetyltransferase 2) • IFNB1 (Interferon Beta 1)
2ms
Mapping herpesvirus-driven impacts on the cellular milieu and transcriptional profile of Kaposi sarcoma in patient-derived mouse models. (PubMed, bioRxiv)
The reproducible expansion of KSHV-infected endothelial cells in PDX from multiple donors and recapitulation of a KS tumor gene signature supports the application of patient-derived KS mouse models for studies of pathogenesis and novel therapies. Tumor virus-driven expansion of endothelial cells with a transcriptional signature of Kaposi sarcoma in a large cohort of patient-derived xenografts provides a platform to discover cell communications within the tumor microenvironment.
Preclinical • Journal
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CXCR4 (Chemokine (C-X-C motif) receptor 4) • CXCL12 (C-X-C Motif Chemokine Ligand 12)
2ms
Structural insights into KSHV-GPCR constitutive activation and CXCL1 chemokine recognition. (PubMed, Proc Natl Acad Sci U S A)
The dual activation mechanism employed by KSHV-GPCR represents an evolutionary adaptation for immune evasion and contributes to the pathogenesis of Kaposi's sarcoma. Together with results from functional assays that confirmed the structural models, these findings may help to develop therapeutic strategies for KSHV infection.
Journal
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CXCR2 (Chemokine (C-X-C motif) receptor 2) • CXCL1 (Chemokine (C-X-C motif) ligand 1)
2ms
In vitro and in vivo evidence of the antineoplastic activity of quercetin against endothelial cells transformed by Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. (PubMed, Biochimie)
Notably, neither kidney nor liver damage was observed, as indicated by biochemical parameters in serum. In conclusion, this study suggests for the first time that QUE exhibits antineoplastic activity in both in vitro and in vivo models of KS, marking a starting point for further investigations and protocols for therapeutic purpose.
Preclinical • Journal
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CASP3 (Caspase 3) • ANXA5 (Annexin A5)
3ms
Cancer Immunotherapy Trials Network 12: Pembrolizumab in HIV-Associated Kaposi Sarcoma. (PubMed, J Clin Oncol)
Pembrolizumab yielded a high rate of durable responses in HIV-associated KS. imAEs were successfully managed with standard guidelines.
Journal
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CD4 (CD4 Molecule)
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Keytruda (pembrolizumab)
3ms
Involvement of Sex Hormones and Their Receptors in the Pathogenesis of Classic Kaposi's Sarcoma in Xinjiang. (PubMed, Skin Res Technol)
Sex hormones and their receptors are implicated in the pathogenesis of CKS in Xinjiang. The use of ER antagonists may represent a novel avenue for research and treatment of CKS.
Journal
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ER (Estrogen receptor) • AR (Androgen receptor)
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AR expression
3ms
KSHV ORF20 Promotes Coordinated Lytic Reactivation for Increased Infectious Particle Production. (PubMed, Viruses)
Finally, expression of IL6 and CXCL8, previously shown to be affected by the hCMV UL24 homolog, was relatively low upon reactivation of cells infected with the ORF20-Null virus. These findings suggest that ORF20 protein, with its putative endonuclease motif, promotes coordinated lytic reactivation for increased infectious particle production.
Journal
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IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8)
|
CXCL8 expression • IL6 expression
3ms
Nivolumab and Ipilimumab in Treating Patients With HIV Associated Relapsed or Refractory Classical Hodgkin Lymphoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)
P1, N=95, Terminated, National Cancer Institute (NCI) | Trial completion date: Sep 2025 --> Aug 2024 | Active, not recruiting --> Terminated; Inadequate accrual rate
Trial completion date • Trial termination
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CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule)
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • ABP 206 (nivolumab biosimilar)
3ms
Nivolumab and Ipilimumab in Treating Patients With HIV Associated Relapsed or Refractory Classical Hodgkin Lymphoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)
P1, N=95, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | Trial completion date: Aug 2024 --> Sep 2025 | Trial primary completion date: Aug 2024 --> May 2024
Enrollment closed • Trial completion date • Trial primary completion date • Surgery • Metastases
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CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule)
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Opdivo (nivolumab) • Yervoy (ipilimumab) • ABP 206 (nivolumab biosimilar)
3ms
Methylation of KSHV vCyclin by PRMT5 contributes to cell cycle progression and cell proliferation. (PubMed, PLoS Pathog)
Remarkably, knockdown or pharmaceutical inhibition (using EPZ015666) of PRMT5 inhibited the cell cycle progression and cell proliferation of KSHV latently infected tumor cells...We also show that the methylation of vCyclin by PRMT5 positively regulates the phosphorylate retinoblastoma protein (pRB) pathway. Taken together, our findings reveal an important regulatory effect of PRMT5 on vCyclin that facilitates cell cycle progression and proliferation, which provides a potential therapeutic target for KSHV-associated malignancies.
Journal
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IL6 (Interleukin 6) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • PRMT5 (Protein Arginine Methyltransferase 5)
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EPZ015666
3ms
Survival Following Diagnosis of HIV-Associated Kaposi Sarcoma Among Adults in East Africa in the "Treat-All" Era. (PubMed, medRxiv)
Among PLWH with newly diagnosed KS in East Africa in the "Treat All" era, survival was poor and related to mucocutaneous extent of KS. The findings emphasize the need for better control of KS in Africa, including novel approaches for earlier detection, better linkage to oncologic care, and more potent therapy.
Journal
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CD4 (CD4 Molecule)
4ms
A Viral-Encoded Homologue of IPS-1 Modulates Innate Immune Signaling During KSHV Lytic Replication. (PubMed, bioRxiv)
Additionally, expression of v-IPS-1 leads to decreased antiviral responses indicating a blot to type I interferon induction during viral infection. Taken together, v-IPS-1 is the first described viral homologue of IPS-1 and this viral protein leads to reprogramming of innate immunity through modulation of type I interferon signaling during KSHV lytic replication.
Journal
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TLR3 (Toll Like Receptor 3)
4ms
The cellular paraspeckle component SFPQ associates with the viral processivity factor ORF59 during lytic replication of Kaposi's Sarcoma-associated herpesvirus (KSHV). (PubMed, Virus Res)
Interestingly, when we tested other human herpesvirus processivity factors (EBV BMRF1, HSV-1 UL42, and HCMV UL44) by transfection of each expression plasmid followed by co-immunoprecipitation, we found a conserved association with SFPQ. These are limited studies that remain to be done in the context of infection but suggest a potential association of SFPQ with processivity factors across multiple herpesviruses.
Journal
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NEAT1 (Nuclear Paraspeckle Assembly Transcript 1)
4ms
Enrollment open
|
CRP (C-reactive protein)
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Vonjo (pacritinib)
4ms
LKB1 suppresses KSHV reactivation and promotes primary effusion lymphoma progression. (PubMed, J Virol)
Compound C, a potent AMPK inhibitor, induced KSHV reactivation and efficiently inhibited PEL progression in vivo. Thus, our work revealed that LKB1 is a potential therapeutic target for KSHV-associated cancers.
Journal
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STK11 (Serine/threonine kinase 11)
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dorsomorphin (Compound C)
4ms
ORF48 is required for optimal lytic replication of Kaposi's sarcoma-associated herpesvirus. (PubMed, PLoS Pathog)
However, the loss of ORF48 in our iSLK-based lytic system failed to induce IFNβ production, suggesting a redundant role of ORF48 on STING signaling during the KSHV lytic phase. Thus, ORF48 is required for optimal KSHV lytic replication through additional mechanisms that need to be further explored.
Journal
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IFNB1 (Interferon Beta 1)
4ms
Kaposi sarcoma and vertebral involvement in people with HIV: a case report and systematic literature review. (PubMed, HIV Res Clin Pract)
Despite progresses in treatment, late presentation of KS, especially with spine involvement may have a poor prognosis. More efforts are needed to promote access to HIV testing, especially when indicating conditions are present.
Review • Journal
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CD4 (CD4 Molecule)
4ms
STARKAP: Preliminary Assessment of Safety and Tolerability of Dostarlimab in Combination Antiretroviral Therapy (cART) Refractory HIV Associated Kaposi Sarcoma (clinicaltrials.gov)
P1, N=20, Recruiting, Imperial College London | Trial completion date: Sep 2025 --> Apr 2026 | Trial primary completion date: May 2024 --> Apr 2026
Trial completion date • Trial primary completion date
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CD4 (CD4 Molecule)
|
Jemperli (dostarlimab-gxly)
4ms
Lobular Capillary Hemangioma: A Rare Bleeding Entity in the GI Tract (ACG 2024)
Although only a handful cases of gastric PG have been reported in the literature, we believe the incidence is higher as they are frequently mistaken for hyperplastic polyps. Figure: Figure 1 & 2
Cologuard®
4ms
Evaluation of PRAME immunohistochemistry in cutaneous vascular neoplasms reveals frequent expression in primary and post-irradiation cutaneous angiosarcomas. (PubMed, J Cutan Pathol)
In this study, we have demonstrated frequent nuclear PRAME expression in cutaneous AS. PRAME immunohistochemistry may serve as a valuable additional marker in selected clinical settings.
Journal
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PRAME (Preferentially Expressed Antigen In Melanoma)