Epstein-Barr virus-driven B cell lymphoma mediated by a direct LMP1-TRAF6 complex

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 10, 2024

Abstract Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) drives viral B cell transformation and oncogenesis. LMP1’s transforming activity depends on its C-terminal activation region 2 (CTAR2), which induces NF-κB JNK by engaging TNF receptor-associated factor 6 (TRAF6). The mechanism of TRAF6 recruitment to LMP1 role in signalling remains elusive. Here we demonstrate that interacts directly with a binding motif within CTAR2. Functional NMR studies supported molecular modeling provide insight into the architecture LMP1-TRAF6 complex, differs from CD40-TRAF6. direct is essential for CTAR2 survival LMP1-driven lymphoma. Disruption complex inhibitory peptides interferes EBV-transformed cells. In this work, identify as critical virus-host interface validate interaction potential therapeutic target EBV-associated cancer.

Language: Английский

---

The cGAS-STING pathway in viral infections: a promising link between inflammation, oxidative stress and autophagy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 15, 2024

The host defence responses play vital roles in viral infection and are regulated by complex interactive networks. immune system recognizes pathogens through the interaction of pattern-recognition receptors (PRRs) with pathogen-associated molecular patterns (PAMPs). As a PRR mainly cytoplasm, cyclic GMP-AMP synthase (cGAS) senses binds virus DNA subsequently activates stimulator interferon genes (STING) to trigger series intracellular signalling cascades defend against invading pathogenic microorganisms. Integrated omic functional analyses identify cGAS-STING pathway regulating various cellular controlling infections. Aside from its most common function inflammation type I interferon, growing body evidence suggests that axis is closely associated responses, such as oxidative stress, autophagy, endoplasmic reticulum which have major impacts on physiological homeostasis. Interestingly, these dual regulation clearance viruses. Here, we outline recent insights into inflammation, autophagy stress discuss their interactions A detailed understanding cGAS-STING-mediated potential antiviral effects contributes revealing pathogenesis certain viruses sheds light effective solutions for therapy.

Language: Английский

---

DNA methylation landscapes before and after Pacific Oyster Mortality Syndrome are different within and between resistant and susceptible Magallana gigas

The Science of The Total Environment, Journal Year: 2025, Volume and Issue: 962, P. 178385 - 178385

Published: Jan. 1, 2025

Language: Английский

---

Epstein-Barr virus-infected nasopharyngeal carcinoma therapeutics: oncoprotein targets and clinical implications

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(3)

Published: Jan. 31, 2025

Language: Английский

---

The role and impact of viruses on cancer development

Periodontology 2000, Journal Year: 2024, Volume and Issue: 96(1), P. 170 - 184

Published: April 20, 2024

Abstract This review focuses on three major aspects of oncoviruses' role in cancer development. To begin, we discuss their geographic distribution, revealing that seven oncoviruses cause 20% all human cancers worldwide. Second, investigate the primary carcinogenic mechanisms, looking at how these oncogenic viruses can induce cellular transformation, angiogenesis, and local systemic inflammation. Finally, possibility SARS‐CoV‐2 infection reactivating latent oncoviruses, which could increase risk further disease. The development oncovirus vaccines holds great promise for reducing burden. Many unanswered questions about host environmental cofactors contribute to prevention remain, ongoing research is attempting address.

Language: Английский

---

The Impact of Oral Microbiome Dysbiosis on the Aetiology, Pathogenesis, and Development of Oral Cancer

Cancers, Journal Year: 2024, Volume and Issue: 16(17), P. 2997 - 2997

Published: Aug. 28, 2024

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Although oral cavity an easily accessible area for visual examination, OSCC more often detected at advanced stage. The global prevalence of around 6%, with increasing trends posing a significant health problem due to increase in morbidity mortality. microbiome has been target numerous studies, findings highlighting role dysbiosis developing OSCC. Dysbiosis can significantly pathobionts (bacteria, viruses, fungi, parasites) that trigger inflammation through their virulence pathogenicity factors. In contrast, chronic bacterial contributes development Pathobionts also have other effects, such as impact on immune system, which alter responses contribute pro-inflammatory environment. Poor hygiene carbohydrate-rich foods risk factors mechanisms are not yet fully understood remain frequent research topic. For this reason, narrative review concentrates issue potential cause OSCC, well underlying involved.

Language: Английский

---

Post-Translational Modifications of cGAS-STING: A Critical Switch for Immune Regulation

Cells, Journal Year: 2022, Volume and Issue: 11(19), P. 3043 - 3043

Published: Sept. 28, 2022

Innate immune mechanisms initiate responses via pattern-recognition receptors (PRRs). Cyclic GMP-AMP synthase (cGAS), a member of the PRRs, senses diverse pathogenic or endogenous DNA and activates innate signaling pathways, including expression stimulator interferon genes (STING), type I interferon, other inflammatory cytokines, which, in turn, instructs adaptive response development. This groundbreaking discovery has rapidly advanced research on host defense, cancer biology, autoimmune disorders. Since cGAS/STING enormous potential eliciting an response, understanding its functional regulation is critical. As most widespread efficient regulatory mode cGAS-STING pathway, post-translational modifications (PTMs), such as covalent linkage groups to amino acid chains, are generally considered mechanism for protein destruction renewal. In this review, we discuss transduction related diseases focus current different modalities PTMs control cGAS-STING-triggered responses.

Language: Английский

---

Epstein–Barr virus LMP1 protein promotes proliferation and inhibits differentiation of epithelial cells via activation of YAP and TAZ

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(20)

Published: May 8, 2023

Latent Epstein–Barr virus (EBV) infection promotes undifferentiated nasopharyngeal carcinomas (NPCs) in humans, but the mechanism(s) for this effect has been difficult to study because EBV cannot transform normal epithelial cells vitro and genome is often lost when NPC are grown culture. Here we show that latent protein, LMP1 (Latent membrane protein 1), induces cellular proliferation inhibits spontaneous differentiation of telomerase-immortalized oral keratinocytes (NOKs) growth factor-deficient conditions by increasing activity Hippo pathway effectors, YAP (Yes-associated protein) TAZ (Transcriptional coactivator with PDZ-binding motif). We demonstrate enhances NOKs both decreasing pathway-mediated serine phosphorylation Src kinase-mediated Y357 YAP. Furthermore, knockdown sufficient reduce promote EBV-infected NOKs. find also required LMP1-induced epithelial-to-mesenchymal transition. Importantly, ibrutinib (an FDA-approved BTK inhibitor blocks through an off-target effect) restores at clinically relevant doses. These results suggest contributes development NPC.

Language: Английский

---

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

Frontiers in Virology, Journal Year: 2023, Volume and Issue: 3

Published: March 6, 2023

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

Language: Английский

---

MOLECULAR AND GENETIC CHARACTERISTICS OF EPSTEIN-BARR VIRUS ISOLATES IN ADULT PATIENTS WITH HIV INFECTION IN NIZHNY NOVGOROD REGION

Russian Journal of Infection and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Abstract Introduction. According to international studies, the Epstein-Barr virus (EBV) isolates from individuals infected with human immunodeficiency (HIV) are characterized by specific molecular genetic features compared immunocompetent individuals. In Russia, no studies have yet been conducted assessing EBV diversity in HIV-patients. The aim of study is assess adult HIV-patients Nizhny Novgorod region. Materials and methods. derived blood leukocytes 138 HIV-infected patients aged 20–69 years (HIV(+) group) 68 HIV-uninfected sex- age-matched (HIV(-) were studied. For differential detection EBV-1/EBV-2, there used PCR variant electrophoretic amplification products agarose gel. Nucleotide sequences C-terminal fragment LMP-1 gene determined Sanger sequencing. Phylogenetic analysis was performed using MEGA X software. Results. typical pattern region adults HIV(-) group, only EBV-1 detected. HIV(+) group rate 88.2±3.4%, EBV-2 – 5.4±2.3%, EBV-1+VEB-2 6.4± 2.6% cases. strain structure based on classification R. Edwards et al. five variants identified: B95-8, China 1, Med-, NC Alaskan, among which B95-8 dominant. However, their frequency did not differ between groups. general, HIV infection, appearance recombinant variants, a wider range deletions, prominent variability tandem repeat presence modified motifs point amino acid substitutions therein noted, 57 described that previously found Conclusion. first time carried out. results obtained build up basis for prospective relationship clinical laboratory characteristics EBV+HIV co-infection heterogeneity population at level types, subvariants.

Language: Английский

---