Search Results (182)

Nucleic acid-based gene interfering and editing molecules, such as antisense oligonucleotides, ribozymes, small interfering RNAs (siRNAs), and CRISPR-Cas9-associated guide RNAs, are promising gene-targeting agents for therapeutic applications. Cancer’s heterogeneous and diverse nature demands gene-silencing technologies that are both specific and adaptable. RNase P ribozymes, called M1GS RNAs, are engineered constructs that link the catalytic M1 RNA from bacterial RNase P to a programmable guide sequence. This guide sequence directs the M1GS ribozyme to base-pair with a target RNA, inducing it to fold into a structure resembling pre-tRNA. Catalytic activity can be enhanced through in vitro selection strategies. In this review, we will discuss the application of M1GS ribozymes in targeting cancer-associated RNAs, focusing on the BCR-ABL transcript in leukemia, the internal ribosome entry site (IRES) of hepatitis C virus (HCV), and the replication and transcription activator (RTA) of Kaposi’s sarcoma-associated herpesvirus (KSHV). Together, these examples highlight the versatility of M1GS ribozymes across both viral and cellular oncogenic targets, underscoring their potential as a flexible synthetic biology platform for cancer therapy. Full article

Kaposi’s sarcoma (KS), an AIDS-defining illness, is caused by Kaposi’s sarcoma-associated herpesvirus (KSHV). A member of the human herpesvirus family, designated as human herpesvirus 8 (HHV-8), KSHV is also linked to other oncogenic manifestations such as primary effusion lymphoma (PEL). The current dearth of available compounds against KSHV necessitates development of effective antiviral treatments. As with other herpesviruses, KSHV can result in both lytic and latent infections. KSHV pathogenesis and the development of KS have been associated with the expression of KSHV genes and transcripts during viral infections. The transcriptome of KSHV heavily intersects with regulatory pathways and mechanisms involved with a multitude of diseases in humans. Circular RNAs (circRNAs) have recently been discovered to be expressed by KSHV. Research endeavors on KSHV circRNAs have focused on the roles they play throughout latent and lytic infection. Understanding the specific functions and interactions of KSHV circRNAs with the viral and host transcriptomes, as well as how they are identified and analyzed, will be the primary focus of this review. Overall, recent advances in KSHV circRNA research have deepened our understanding of the KSHV transcriptome and pathogenesis and are paving the way for the development of circRNA-based antiviral therapies. Full article

Background: Kaposi sarcoma (KS) is a human herpesvirus-8-associated vascular malignancy with four subtypes. Although several local therapies are available for cutaneous lesions, no standard treatment exists. Laser therapy is a minimally invasive treatment option; however, its efficacy and safety remain unclear. Objectives: To systematically review and analyze the available literature on the efficacy and safety of laser-based treatment protocols for cutaneous KS lesions. Methods: A comprehensive literature search was conducted up to August 2025 to identify randomized controlled trials, observational studies, and case series with ≥3 patients who received laser therapy for cutaneous KS. Data on patient and disease characteristics, laser protocols, outcomes and adverse events were extracted from the included studies. Results: Eight studies involving 79 patients with 371 treated lesions were included in this systematic review. The reported outcome rates varied greatly between different modalities, with inconsistent outcome definitions. No recurrence was reported in seven studies, whereas the condition in all cases in the eighth study recurred. Overall, laser therapy was well tolerated with minimal adverse effects, including mild atrophic scarring, transient post-inflammatory changes, and hyperpigmentation. Six studies were eligible for meta-analysis, yielding a pooled significant response rate of 88% (95% CI: 44.1–98.6%, I² = 86.3%). Conclusions: Available data indicate that laser therapy may represent a safe and effective option for cutaneous KS, particularly Nd:YAG, which demonstrated good efficacy with low recurrence rates; however, further research is required to define its efficacy more precisely and to standardize treatment protocols. Full article

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma (KS) and several lymphoproliferative diseases. As with all herpesviruses, KSHV replicates in a biphasic manner, with the establishment of a latent, persistent infection from which reactivation occurs, resulting in the completion of the temporal lytic replication cycle and production of infectious virions. Herein, we discuss the impact of KSHV lytic replication on the host cell nucleus and nuclear-related pathways. We highlight the dramatic remodelling of the nuclear architecture driven by the formation of viral replication and transcription centres (vRTCs), and the implications for sub-nuclear organelles, and how pathways involved in DNA damage, ribosomal biogenesis and epitranscriptomic regulation are disrupted or modified during KSHV replication. These changes foster an environment favourable for KSHV replication and may provide novel targets and strategies for therapeutic intervention. Full article

Kaposi’s sarcoma (KS) is a tumor that primarily affects the skin, caused by a multifactorial pathogenesis mediated through immune dysfunction, often leading to increased morbidity and mortality in Sub-Saharan Africa (SSA). Human herpesvirus-8, also known as Kaposi’s sarcoma-associated herpesvirus (KSHV), induces an infection that can facilitate the pathogenesis of KS and other conditions. All KSHV subtypes depend on the expression of specific markers, such as K1 proteins, which play critical roles in their life cycles. The infection is unevenly scattered worldwide, with individuals infected with human immunodeficiency virus (HIV) and pregnant women being among the most vulnerable groups. HIV infection and related effectors, such as TAT proteins, have substantial impacts on KSHV infectiousness, angiogenesis, various signaling pathways, and KS pathogenesis. Africa endures the heaviest burden of KS, which affects both men and women, sometimes from an early age. KS’s pathogenesis and underlying mechanisms remain unclear; this study aims to highlight the dynamics to be considered in managing and mitigating the burden of KS in SSA. In that region, certain infections are endemic and can cause intermediate health damage leading to KS tumorigenesis, highlighting the link between non-communicable and communicable diseases. Full article

Kaposi sarcoma (KS) is an intermediate-grade vascular tumour that has undergone major treatment and diagnostic breakthroughs following the discovery of Human herpesvirus 8 (HHV8). Whilst classically described in Eastern European populations, the endemic and epidemic forms of KS have facilitated its association with AIDS. This was led by the detection of HHV8 by PCR, and thereafter, immunohistochemically. This not only enabled the recognition and diagnosis of complex histopathological KS subtypes but also facilitated distinction from its mimickers, including acroangiodermatitis and pyogenic granuloma. Recent advances in the viral genomics of HHV8 have expanded the diagnostic landscape of KS clinically and molecularly. The latent phase of replication in the HHV8 lifecycle reveals numerous angiogenic and inflammatory factors. Novel therapies targeting these viral–human molecular interactions may prove useful. However, this is highly dependent on the clonal nature of KS. Conflicting research outcomes demonstrate varying viewpoints on the clonal (monoclonal/oligoclonal/polyclonal) nature of KS, heightening the tumoural versus inflammatory pseudoneoplastic controversy. Understanding the clinical context of KS is fundamental to understanding its clonality, and a dearth of this clinical information in recent studies appears to be the critical factor in determining the true clonal nature of KS. The current molecular landscape, histopathology, treatment options, and opinions on clonality are critically reviewed. Full article

Human herpesvirus-8 (HHV-8)-associated multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder with systemic and cutaneous manifestations that can be diagnostically challenging, especially in immunocompromised patients. We report the case of a 68-year-old man with HIV and biopsy-proven Kaposi sarcoma (KS), who developed progressive fevers, night sweats, weight loss, and fatigue, accompanied by diffuse lymphadenopathy, splenomegaly, and new erythematous and hyperpigmented lesions shortly after intravenous immunoglobulin therapy for Guillain–Barré syndrome. A laboratory evaluation revealed that the patient had elevated total protein and polyclonal hypergammaglobulinemia, without monoclonality. Imaging demonstrated widespread lymphadenopathy and splenomegaly. A core lymph node biopsy showed polytypic plasmacytosis, but was non-diagnostic. Given the ongoing symptoms, an excisional biopsy was performed, revealing regressed germinal centers with increased interfollicular vascularity, mantle zone “onion skinning,” and HHV-8 LANA-1 nuclear positivity, establishing the diagnosis of HHV-8-associated MCD. Rituximab monotherapy was initiated, resulting in clinical improvement, resolution of the constitutional symptoms, and stabilization of ascites. This case highlights the importance of maintaining a high index of suspicion for MCD in patients with KS who develop new systemic or cutaneous findings, the limitations of a core biopsy, and the value of a timely excisional biopsy in guiding diagnosis and treatment. Full article

Background/Objectives: Angioimmunoblastic T-cell lymphoma (AITL) is a rare peripheral T-cell lymphoma of follicular helper T-cell (TFH) origin, often associated with immune dysregulation and EBV-positive B-cell proliferation. Kaposi sarcoma (KS) is a vascular neoplasm caused by human herpesvirus 8 (HHV-8), typically arising in immunocompromised individuals. The synchronous occurrence of AITL and KS in HIV-negative patients is exceptionally rare, with only three cases previously reported worldwide. Case Presentation: We describe an 81-year-old HIV-negative Korean woman presenting with progressive generalized edema and dyspnea. Imaging revealed multifocal lymphadenopathy. Excisional biopsy of the inguinal lymph node showed two distinct but adjacent neoplastic processes. The AITL component demonstrated a polymorphous infiltrate of atypical TFH cells expressing CD3, CD4, CD10, PD-1, and Bcl-6, with monoclonal TCR-γ rearrangement and TET2 and RHOA mutations. The KS component comprised spindle cells with slit-like vascular spaces, red blood cell extravasation, and immunoreactivity for HHV-8, CD31, CD34, and ERG. The findings were consistent with a collision tumor. Despite supportive care, the patient’s condition deteriorated, and she was discharged with palliative care. Discussion: The coexistence of AITL and KS in an HIV-negative setting raises important pathogenetic considerations. AITL is characterized by profound immune dysregulation, with depletion of normal T-cell subsets, abnormal B-cell activation, and cytokine milieu changes that may favor latent viral reactivation. This immunologic environment may permit HHV-8 reactivation, thereby facilitating the development of KS even in the absence of overt immunodeficiency due to HIV infection. Our findings support the hypothesis that AITL-related immune dysfunction may create a permissive niche for HHV-8-driven neoplasia. Conclusions: This is the first reported case in Asia and the fourth worldwide of a collision tumor comprising AITL and KS in an HIV-negative patI dient. The case suggests that AITL-associated immune dysregulation may facilitate HHV-8 reactivation and KS development even in the absence of HIV infection. Awareness of this association is critical for accurate diagnosis and optimal patient management. Full article

Castleman disease and Kaposi sarcoma (KS) are both associated with infection by human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). This virus plays a critical role in the pathogenesis of both conditions, particularly in immunocompromised individuals, such as those with HIV/AIDS. Multicentric Castleman disease (MCD) generally presents with systemic inflammatory symptoms, lymphadenopathy, and organ dysfunction, while Kaposi sarcoma typically appears as vascular tumors on the skin, with occasional involvement of mucous membranes or internal organs. We present four clinical cases, with concurrent KS and MCD, treated with chemotherapy and rituximab, with a satisfactory response. We highlighted the essential role of prompt investigation of systemic or inflammatory manifestations (fever, vital parameter alterations such as palpitation, high breath frequency, edema, and kidney impairment) as underlined in our case series, which might underscore possible complications. Multiorgan failure, opportunistic infections, or rapid clinical deterioration might occur if the diagnosis is not adequately assessed. Therefore, this paper emphasizes the importance of timely diagnosis, as it enables the prompt initiation of appropriate antiviral, immunomodulatory, or oncologic therapies—interventions that can significantly improve outcomes and may be life-saving in advanced or aggressive disease presentations. Full article

Porcine lymphotropic herpesviruses -1, -2, and -3 (PLHV-1, PLHV-2, and PLHV-3) are gammaherpesviruses that are widespread in pigs. These viruses are closely related to the human pathogens Epstein–Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), both of which are known to cause severe diseases in humans. To date, however, no definitive association has been established between PLHVs and any disease in pigs. With the growing interest in xenotransplantation as a means to address the shortage of human organs for transplantation, the safety of using pig-derived cells, tissues, and organs is under intense investigation. In preclinical trials involving pig-to-nonhuman primate xenotransplantation, another porcine herpesvirus—porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV)—was shown to be transmissible and significantly reduced the survival time of the xenotransplants. In the present study, we examined donor pigs and their respective baboon recipients, all of which were part of preclinical pig heart xenotransplantation studies, for the presence of PLHV. PLHV-1, PLHV-2, and PLHV-3 were detected in nearly all donor pigs; however, no evidence of PLHV transmission to the baboon recipients was observed. Full article

Oncoviruses, such as Epstein–Barr virus (EBV), human papillomavirus (HPV), and Kaposi sarcoma-associated herpesvirus (KSHV), have been widely discussed for their oncogenic risk. Initially, the oral cavity was disregarded. In recent years, orientation has shifted to the importance of the oral cavity and cancer-related issues via Handbook 19 titled “Oral Cancer Prevention” by the International Agency for Research on Cancer, the WHO Global Oral Health Status Report 2022, and multiple other actions focused on reducing the oversight of this neglected area. Oncoviruses play a significant role in oral cavity malignancies by establishing persistent infections, evading host immune responses, and inducing cellular transformation through the disruption of normal regulatory pathways. Molecular biology and microbiome research have advanced our understanding of the complex interplay between oncoviruses and oral microbiota, demonstrating how coinfections and dysbiosis can enhance viral oncogenic potential. These findings improve the understanding of virus-induced oral cancers and support the development of novel diagnostic and therapeutic strategies. This narrative review focuses on the relationship between oncoviruses and the oral cavity by focusing on how a specific virus triggers tumorigenesis for each of the described viruses and how it affects oral cavity cancer development. Finally, we describe recent advances and future perspectives including vaccines and/or treatment. Full article

AIDS-related malignant lymphomas (ARLs) are the lymphomas that develop in association with HIV infection. According to the introduction of combination antiretroviral therapy (cART), the life expectancy of People Living with HIV (PLWH) has markedly improved; however, approximately one-third of PLWH have passed away from the complications of malignancies, even in well-controlled PLWH. HIV itself is not tumorigenic, and most of these tumors are due to co-infection with oncogenic viruses. γ-herpes viruses (Epstein–Barr virus: EBV and Kaposi sarcoma-associated herpesvirus: KSHV) are the most significant risk factors for ARLs. Immunodeficiency, chronic inflammation, accelerated aging, and genetic instability caused by HIV infection, as well as HIV accessory molecules, are thought to promote lymphomagenesis. The prognosis of ARLs is comparable to that of non-HIV cases in the cART era. Intensive chemotherapy with autologous stem cell transplantation is also available for relapsed/refractory ARLs. Since the early stage of HIV infection has no symptoms, significant numbers of HIV-infected individuals have not noticed HIV infection until the onset of AIDS (so-called Ikinari AIDS). Since the ratio of these patients is more than 30% in Japan, hematologists should carefully consider the possibility of HIV infection in cases of lymphoma. Even in an era of cART, ARL remains a critical complication in PLWH, warranting continuous surveillance. Full article

Although efficiently managed by cART, chronic HIV infection remains associated with a high incidence of malignant lymphomas. This diverse group of tumors presents considerable challenges in research, diagnosis, and treatment due to their complex pathogenesis, heterogeneous tumor microenvironment, and frequently aggressive clinical behavior. In this review, we examine the multifactorial pathogenesis of lymphomas arising in people living with HIV (PLWH), encompassing both direct and indirect oncogenic mechanisms. We summarize the key histopathological features and microenvironmental characteristics that may influence therapeutic responses. Current treatment strategies approved for the treatment of lymphomas in PLWH are showing outcomes comparable with those observed in patients without HIV. Notably, the immune reconstitution achieved through cART has renewed interest in immunotherapeutic approaches for HIV-associated lymphomas, with several strategies under clinical investigation. However, progress in the diagnosis and management of these malignancies is hindered by fragmented research efforts and the frequent exclusion of PLWH from pivotal clinical trials. Coordinated efforts are essential to overcome these barriers, reduce lymphoma incidence, and improve survival outcomes in this vulnerable population. Full article

Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, is regulated by key mediators including glutathione peroxidase 4 (GPX4) and nuclear factor erythroid 2-related factor 2 (Nrf2). Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes latency-associated nuclear antigen (LANA), a multifunctional protein critical for viral persistence. Although studies reported that KSHV infection enhanced cellular resistance to ferroptosis, the specific role of LANA in this process remains unexplored. Here, we demonstrate that LANA unexpectedly promotes ferroptosis. In KSHV-positive iSLK.219 cells, LANA knockdown significantly attenuated RSL-3-induced ferroptosis, whereas LANA overexpression sensitized HeLa cells to ferroptotic death. Quantitative analysis revealed that LANA-depleted cells exhibited significantly elevated ROS accumulation (p < 0.01), whereas LANA-overexpressing cells maintained reduced ROS levels during challenge with the ferroptosis inducer RSl-3. Mechanistically, LANA suppressed glutathione peroxidase 4 (GPX4) expression, reduced nuclear factor erythroid 2-related factor 2 (Nrf2) expression and impaired its nuclear translocation, and upregulated mouse double minute 2 homolog (MDM2) expression. Pharmacological inhibition of Nrf2 (ML385) or MDM2 (nutlin3a) reversed the ferroptotic effects of LANA knockdown or overexpression, respectively. These findings reveal a pro-ferroptotic role of LANA via Nrf2/GPX4 suppression and MDM2 activation. Full article

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic double-stranded DNA virus. There are no vaccines or antiviral therapies for KSHV. Identifying the cellular metabolic pathways that KSHV manipulates can broaden the knowledge of how these pathways contribute to sustaining lytic infection, which can be targeted in future therapies to prevent viral spread. In this study, we performed an untargeted metabolomic analysis of KSHV infected telomerase-immortalized gingival keratinocytes (TIGK) cells at 4 h post-infection compared to mock-infected cells. We found that the metabolomic landscape of KSHV-infected TIGK differed from that of the mock. Specifically, a total of 804 differential metabolic features were detected in the two groups, with 741 metabolites that were significantly upregulated, and 63 that were significantly downregulated in KSHV-infected TIGK cells. The differential metabolites included ornithine, arginine, putrescine, dimethylarginine, orotate, glutamate, and glutamine, and were associated with pathways, such as the urea cycle, polyamine synthesis, dimethylarginine synthesis, and de novo pyrimidine synthesis. Overall, our untargeted metabolomics analysis revealed that KSHV infection results in marked rapid alterations in the metabolic profile of the oral epithelial cells. We envision that a subset of these rapid metabolic changes might result in altered cellular functions that can promote viral lytic replication and transmission in the oral cavity. Full article