Aug 2026· Journal of Neurovirology· Vol 32· 0 citations· 76 references
Medicine
TL;DR
This review highlights how neurotropic viruses co-opt epigenetic pathways to drive neurodegeneration and explores biomarker-driven strategies for personalized interventions in neurodegenerative disorders thus emphasizing potential epigenetic editing tools to restore neuronal homeostasis.
Circular RNAs (circRNAs) represent a class of highly stable, covalently closed RNA molecules increasingly recognized as important regulators of brain aging and neurodegenerative disease. Growing evidence also implies circRNAs in viral infection, suggesting a potential intersection between viral neuropathogenesis and neurodegeneration. However, no studies have yet directly integrated circRNAs, neurotropic viral infections, and neurodegenerative disorders within a single mechanistic framework. To date, specific circRNAs have been linked to the progression of Alzheimer’s disease and Parkinson’s disease, where they regulate central pathological processes including amyloid-β clearance, neuroinflammation, synaptic plasticity, neuronal apoptosis, and oxidative stress. Moreover, it has been established that both host cells and viruses produce circRNAs during infection. Virus-derived circRNAs can enhance viral replication, promote immune evasion, and support latency. In contrast, host circRNAs contribute to antiviral defense by acting as microRNA sponges, interacting with viral proteins, or encoding peptides with antiviral activity, mechanisms particularly explored in viral oncogenesis. In this review, we will evaluate the most updated research evidence on the role of circRNAs in major neurodegenerative diseases and neurotropic viral infections. Considering the growing concern regarding the long-term neurological consequences of viral infections, including chronic neuroinflammation, viral reactivation, and post-viral syndromes, dysregulated circRNAs may represent a mechanistic link between viral infection and associated neurodegenerative processes. Finally, we will discuss future directions for identifying circRNAs-based biomarkers and developing circRNAs-targeted therapeutic strategies for age-related and virus-associated neurological disorders.
Finley Medina, Anna Bellizzi· Journal of Neurovirology· 0 citations
The DNA damage response (DDR) network maintains genomic integrity, functions as a signaling hub that viruses exploit to drive pathogenesis, and constitutes a central interface between viral infection and host cell fate. This review discusses the molecular mechanisms by which viruses subvert host DDR pathways, with an emphasis on viral replication, latency, immune evasion, and host genomic instability. Representative examples include PARP1-dependent cccDNA stabilization by hepatitis B virus (HBV), MRN complex sequestration by herpes simplex virus type 1 (HSV-1) for immune evasion, ATM signaling modulation by human immunodeficiency virus (HIV) to maintain viral latency, and DDR activation triggered by RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus (ZIKV), and influenza A virus (IAV) via oxidative stress. We evaluate emerging DDR-targeted antiviral strategies, including restoring intrinsic host restriction, exploiting synthetic lethality of dysregulated DDR kinases, and therapeutically modulating DDR-innate immune crosstalk to restore antiviral surveillance (e.g., by stabilizing MRE11 or inhibiting PARP7). Bridging molecular insights with clinical translation, this review positions DDR targeting as a mechanism-driven, host-directed antiviral paradigm.
Cancer hallmarks are characterized by wide-scale changes in gene expression programs. Pioneering studies showed how viral oncogenes target regulatory pathways, but little is known about tumorigenic mechanisms of non-viral pathogens. Theileria annulata is an intracellular parasite (related to apicomplexa parasites causing malaria) which remarkably transforms bovine leukocytes, hijacking host signaling pathways to induce cancer phenotypes, akin to human leukemias. While some host genes contribute to the proliferative or invasive hallmark phenotypes, there is still limited comprehensive understanding of the impact of Theileria infection on host transcription and transformation. We performed a multi-omics meta-analysis to investigate the effect of Theileria infection on cancer hallmarks in bovine B lymphocytes. Combining transcriptomic, proteomic and epigenomic analysis across multiple datasets, we show that Theileria infection suppresses host immune pathways. Specifically, genes encoding innate and adaptive immune mediators are repressed in T. annulata-infected B cells (and in T. parva infected T cells), including downregulation of genes for Toll-like receptors (TLR), inflammasome components of the guanylate binding protein (GBP) family and major histocompatibility complex class (MHC) II genes. Treatment with distinct theilericidal drugs could partially rescue immune gene expression. Mechanistically, we describe alterations in the host epigenome, including loss of activating histone modifications (e.g., H3K18ac, H3K4me3, H3K27ac) on the promoters of repressed immune genes, and enrichment of silencing marks (H3K27me3) on promoters of the BOLA genes and the gene encoding CIITA, the master transcriptional regulator of MHC class II gene expression. Our results suggest that intracellular T. annulata and T. parva parasites could drive an immune evasion cancer hallmark in host lymphocytes by epigenetic silencing of genes for innate and adaptive immunity.
Marisol Giacomini, Aristeidis Panagiotou, Steve G. Odette et al.· PLoS Pathogens· 0 citations
Viral infections are a major contributor to global cancer incidence and mortality. However, integrative reviews that connect viral classification, carcinogenic mechanisms, tumor microenvironment remodeling, and translational strategies remain limited. This review summarizes the classification and epidemiological characteristics of major oncogenic viruses, including human papillomavirus (HPV), Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Merkel cell polyomavirus (MCPyV), human T-lymphotropic virus type 1 (HTLV-1), Kaposi’s sarcoma-associated herpesvirus (KSHV), and human immunodeficiency virus (HIV), as well as emerging viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We then discuss the molecular basis of virus-associated carcinogenesis, including viral oncogenes, viral DNA integration, epigenetic remodeling, aberrant host signaling, and metabolic dysregulation. We further examine how chronic inflammation and fibrosis create oncogenic niches within the tumor microenvironment (TME), how viruses promote tumor progression through immune evasion and immune exhaustion, and how infected cells interact with stromal and immune components of the TME. At the preventive and therapeutic levels, we discuss antiviral therapies, vaccines, biomarker-based precision diagnostics, and prognostic strategies, with particular attention to the synergistic potential of emerging therapeutic approaches such as immune checkpoint inhibitors (ICIs), CAR-T therapy, and oncolytic viruses (OVs). Finally, we highlight how multi-omics approaches, single-cell transcriptomics, spatial transcriptomics, organoid models, and artificial intelligence can advance mechanistic studies and translational innovation in virus-associated cancers. Overall, this review provides an integrated framework for understanding, preventing, and treating virus-associated tumorigenesis.
Persistent infection with high-risk human papillomavirus (HR-HPV) is the primary driver of cervical cancer; however, viral presence alone is insufficient to induce malignancy. The progression from initial infection to invasive carcinoma requires a coordinated series of alterations in both the viral genome and the host cell's regulatory machinery. This review focuses on three principal mechanisms by which HR-HPV bypasses host regulatory controls: epigenetic modifications, immune evasion, and endocrine signaling. Specifically, we describe how the viral oncoproteins E6 and E7 recruit host DNA methyltransferases—particularly DNMT1, DNMT3A, and DNMT3B—to silence tumor suppressor genes such as CCNA, hTERT, and E-cadherin via promoter hypermethylation. Beyond DNA methylation, HPV disrupts histone acetylation and methylation patterns through interactions with p300/CBP, the NuRD complex, and Polycomb group proteins, while simultaneously dysregulating non-coding RNAs and specific microRNAs to reinforce this transcriptionally silenced state. The review further details how HPV escapes immune clearance by driving a Th1-to-Th2 cytokine shift, downregulating MHC class I expression, and recruiting myeloid-derived suppressor cells and regulatory T cells to the cervical microenvironment. Additionally, we discuss the role of cofactors, focusing on the synergistic interaction between estradiol and HPV oncogenes; this interaction promotes local immunosuppression via estrogen receptor alpha signaling on stromal fibroblasts and infiltrating immune cells. We also examine the contribution of high parity as a key epidemiological risk factor. A comparative analysis of patient data across three distinct studies is presented to illustrate how demographic and reproductive variables correlate with cervical lesion severity in different populations. Ultimately, cervical carcinogenesis stems from multi-pathway interactions where viral oncogenes, epigenetic changes, immune escape, and hormonal factor
Anindita Kundu, B. Chaudhuri, P. Guchhait et al.· East African Scholars Journa...· 0 citations
The Epstein-Barr virus (EBV) has evolved complex mechanisms to manipulate the host immune system and epigenetic machinery, enabling it to establish lifelong latent infection within host cells. Emerging evidence strongly indicates that the EBV acts as a main epigenetic manipulator by silencing host regulatory genes, altering host chromatin landscapes and exploiting B-cell biology. Key mechanisms include viral-mediated recruitment of host DNA methyltransferases and histone-modifying enzymes; modulation of host non-coding RNAs and chromatin architectural factors; and targeted disruption of interferon signaling through RNA methylation and restructuring of host chromatin. These integrated processes allow EBV to maintain a lifelong infection in humans, evade both innate and adaptive immunity, and respond to reactivation signals. Understanding the virus-host epigenetic interplay offers new opportunities for therapeutic interventions targeting epigenetic regulators in EBV-associated diseases.
Sanaz Baghban Rahimi, Ahmad Hosseinzadeh Adli, Hossein Bannazadeh Baghi et al.· Clinical Epigenetics· 0 citations
