Search Results (155)

Marek’s disease (MD), induced by the highly contagious Marek’s disease virus (MDV), remains a significant challenge to global poultry health despite extensive vaccination efforts. This study employed integrated transcriptomic and metabolomic analyses to investigate liver responses in naturally MDV-infected Wenchang chickens during late infection stages. RNA sequencing identified 959 differentially expressed genes (DEGs) between the infected and uninfected groups. Functional enrichment analysis demonstrated that these DEGs were primarily associated with canonical pathways related to metabolism and cellular processes, including lipid, carbohydrate, and amino acid metabolism, as well as the p53 signaling pathway, cell cycle, and apoptosis. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) detected 561 differentially expressed metabolites (DEMs), showing near-significant enrichment (p = 0.069) in phenylalanine metabolism. Integrated analysis of transcriptomics and metabolomics data highlighted that critical gene–metabolite pairs such as SGPL1-palmitaldehyde–sphinganine-1-phosphate and ME1-NADP+–malic acid potentially mediate functional crosstalk between sphingolipid metabolism and cellular redox homeostasis during viral oncogenesis. This comprehensive mapping of regulatory networks provides insights into host–virus interactions during MDV pathogenesis, offering potential applications in immunomodulation approaches, targeted therapeutic strategies, and vaccine adjuvant development. Full article

Herpesviruses are DNA viruses that evade the immune response and persist as lifelong infections. Human gamma-herpesviruses Epstein–Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV) are oncogenic; they can lead to cancer. Oncogenic viruses are responsible for 10–15% of human cancer development, which can have poor prognoses. Non-coding RNAs (ncRNAs) are RNAs that regulate gene expression without encoding proteins, and are being studied for their roles in viral immune evasion, infection, and oncogenesis. ncRNAs are classified by their size, and include long non-coding RNAs, microRNAs, and circular RNAs. EBV and KSHV manipulate host ncRNAs, and encode their own ncRNAs, regulating host processes and immune responses. Viral ncRNAs regulate host functions by post-transcriptionally modifying host RNAs, and by serving as mimics of other host RNAs, promoting immune evasion. ncRNAs in gamma-herpesvirus infection are also important for tumorigenesis, as dampening immune responses via ncRNAs can upregulate pro-tumorigenic pathways. Emerging topics such as RNA modifications, target-directed miRNA degradation, competing endogenous RNA networks, and lncRNA/circRNA–miRNA interactions provide new insights into ncRNA functions. This review compares ncRNAs and the mechanisms of viral immune evasion in EBV and KSHV, while also expanding on recent developments in the roles of ncRNAs in immune evasion, viral infection, and oncogenesis. Full article

Oncogenic viruses are infectious agents that can cause cancer in humans and animals. They are estimated to be responsible for approximately 12% of human cancers worldwide. These viruses trigger a series of mechanisms that allow them to insert their genetic material into host cells, disrupting normal cellular processes and leading to uncontrolled growth and tumor formation. This article reviews the literature on the main oncogenic viruses and reports on newly identified viruses potentially associated with cancer development, addressing the mechanisms of oncogenesis and the types of cancers associated. In addition, the article brings together the evidence for preventive strategies, such as vaccination, and therapeutic advances in combating oncogenic viral infections. This review discusses the role of early detection and treatment in managing virus-related cancers globally. This article reviews current prevention and treatment strategies, including HPV and HBV vaccines and antiviral therapies, and mentions future approaches like immunotherapies and CRISPR/Cas9. Therefore, this article underscores the importance of studying the dynamics of co-infection and the role of human microbiota in viral persistence and carcinogenesis, which opens new possibilities for combination therapies and microbiome-based interventions to slow the progression of viral-related tumors. Full article

Background/Objectives: Breast cancer (BC) is the most common source of new cancer diagnoses among women and the second leading cause of cancer-related deaths in this group. The role of viral factors in the etiology, heterogeneity, and pathogenesis of this disease and its subtypes has not been incontrovertibly determined. Thus, in this study we began to address this problem by testing the hypothesis that the oncogenic Epstein–Barr virus (EBV) plays a role in this process. The approach involved determining the differential expression and predicted role of EBV gene sequences present in various subtypes of breast tumors as compared to those in control normal tissues. Methods: We utilized existing deep sequencing RNA-seq datasets derived from seventeen breast tumors and three control normal breast tissue samples to investigate the differential expression of EBV gene sequences. Results: We report three-fold higher levels of normalized total EBV-expressed sequences in tumors as compared to in control breast tissue. We also demonstrate differential expression of EBV gene transcript sequences in four categories of 26 known genes in breast cancer tumors as compared to that in normal breast tissue controls. Tumor-specific expression of EBV gene transcript sequences localized to seventeen genes; of these, tumor-specific EBV gene transcript-expressed sequences localizing to nine genes were strongly differentially expressed in a breast cancer subtype-specific manner. Furthermore, in a proof-of-concept investigation, we report, for the first time, that functional analysis of the differentially expressed integrated EBV transcript sequences demonstrate the capacity of these sequences to generate novel EBV miRNAs. We conclude that these integrated EBV sequences could potentially play a role in the pathogenesis of BC and its most aggressive subtypes. The functional role of these findings is currently under study. Full article

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased substantially over the past three decades, and since 2017, it has been recognized in the AJCC staging system as distinct from its HPV-negative counterpart. The underlying mechanisms of HPV-associated carcinogenesis, tumor microenvironment, and host immune response represent opportunities for therapeutic development. While anti-PD-1 immunotherapy is now part of standard treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in general, there are no established immunotherapeutic strategies specifically for HPV-related HNSCC. In this context, multiple emerging approaches are being actively studied—among these are therapeutic vaccines with or without anti-PD-(L)1 adjuvants, peptide–HLA-based immunotherapeutic platforms, and adoptive cell therapies including tumor-infiltrating lymphocytes (TILs), T-cell receptor (TCR) therapy, and chimeric antigen receptor (CAR) T-cell therapy. Beyond further maturation of these novel immunotherapeutic strategies, additional work is needed to delineate the optimal disease state of application (localized versus recurrent/metastatic), as well as in the development of small molecule inhibitors targeting HPV-specific mechanisms of viral oncogenesis. Full article

Human T-lymphotropic viruses (HTLVs) are deltaretroviruses infecting millions of individuals worldwide, with HTLV-1 and HTLV-2 being the most widespread and clinically relevant types. HTLV-1 is associated with severe diseases such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), while HTLV-2 shows a lower pathogenic potential, with occasional links to neurological disorders. HTLV-3 and HTLV-4, identified in Central Africa, remain poorly characterized but are genetically close to their simian counterparts, indicating recent zoonotic transmission events. HTLVs replicate through a complex cycle involving cell-to-cell transmission and clonal expansion of infected lymphocytes. Viral persistence is mediated by regulatory and accessory proteins, notably Tax and HBZ in HTLV-1, which alter host cell signaling, immune responses, and genomic stability. Integration of proviral DNA into transcriptionally active regions of the host genome may contribute to oncogenesis and long-term viral latency. Differences in viral protein function and intracellular localization contribute to the distinct pathogenesis observed between HTLV-1 and HTLV-2. Geographically, HTLV-1 shows endemic clusters in southwestern Japan, sub-Saharan Africa, the Caribbean, South America, and parts of the Middle East and Oceania. HTLV-2 is concentrated among Indigenous populations in the Americas and people who inject drugs in Europe and North America. Transmission occurs primarily via breastfeeding, sexual contact, contaminated blood products, and, in some regions, zoonotic spillover. Diagnostic approaches include serological screening (ELISA, Western blot, LIA) and molecular assays (PCR, qPCR), with novel biosensor and AI-based methods under development. Despite advances in understanding viral biology, therapeutic options remain limited, and preventive strategies focus on transmission control. The long latency period, lack of effective treatments, and global neglect complicate public health responses, underscoring the need for increased awareness, research investment, and targeted interventions. Full article

This perspective examines the potential oncogenic mechanisms of SARS-CoV-2 through comparative analysis with established cancer-causing viruses, integrating classical virological approaches with artificial intelligence (AI)-driven analysis. The paper explores four key themes: shared oncogenic mechanisms between classical viruses and SARS-CoV-2 (including cell cycle dysregulation, inflammatory signaling, immune evasion, and metabolic reprogramming); the application of AI in understanding viral oncogenesis; the integration of neuroimaging evidence; and future research directions. The author presents novel hypotheses regarding SARS-CoV-2’s potential oncogenic mechanisms, supported by recent PET/FDG imaging studies showing persistent metabolic alterations. The manuscript emphasizes the transformative potential of combining traditional virological methods with advanced AI technologies for better understanding and preventing virus-induced cancers, while highlighting the importance of long-term monitoring of COVID-19 survivors for potential oncogenic developments. Full article

Human viral infections remain a significant global health challenge, contributing to a substantial number of cancer cases worldwide. Among them, infections with oncoviruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) are key drivers of hepatocellular carcinoma (HCC). Despite the availability of an effective HBV vaccine since the 1980s, millions remain chronically infected due to the persistence of covalently closed circular DNA (cccDNA) as a reservoir in hepatocytes. Current antiviral therapies, including nucleos(t)ide analogs and interferon, effectively suppress viral replication but fail to eliminate cccDNA, underscoring the urgent need for innovative therapeutic strategies. Direct-acting antiviral agents (DAAs), which have revolutionized HCV treatment with high cure rates, offer a promising model for HBV therapy. A particularly attractive target is the intrinsically disordered region (IDR) of the HBx protein, which regulates cccDNA transcription, viral replication, and oncogenesis by interacting with key host proteins. DAAs targeting these interactions could inhibit viral persistence, suppress oncogenic signaling, and overcome treatment resistance. This review highlights the potential of HBx-directed DAAs to complement existing therapies, offering renewed hope for a functional HBV cure and reduced cancer risk. Full article

South Africa has the highest HIV prevalence globally, often co-occurring with helminth infections in impoverished regions. The coexistence of these infections leads to immunological interactions, potentially enhancing oncogenesis by upregulating immune checkpoint molecules (ICs) among other effects. Notably, most ICs are overexpressed in cancer and correlated with its progression. Helminth infections trigger Th2-type immunity, increasing immunosuppressive M2 macrophages, regulatory T cells, and associated IC molecules. PD-L2 is reported to contribute to Th2-type immunity induced by helminth infections. Similarly, TIM-3, elevated during chronic viral infections, induces a similar immunosuppressive profile. CTLA-4 and PD-1 impact T-cell function by interacting with CD28, crucial for T-cell function. CD28 is downregulated in chronic infections and cancer. This study investigated the impact of HIV-helminth co-infection on co-stimulatory and co-inhibitory molecule profiles associated with antitumor immunity. Using 78 serum samples collected from March 2020 to May 2021, participants were categorized into uninfected control (no HIV and helminth infections), HIV-infected, helminth-infected, and HIV-helminth co-infected groups. Multiplex immune regulatory molecule assay analysis was conducted. The data were analyzed using multivariate regression analysis and adjusted for confounders (age, gender, BMI, ART, supplements, and other chronic diseases). The uninfected control group was used as the baseline reference group for analysis. HIV-infected individuals had higher PD-1 (adjusted β = 0.12, p = 0.034) and TIM-3 (adjusted β = 23.15, p = 0.052) levels, with the latter showing a trend toward significance. However, lower CD28 levels (adjusted β = −651.95, p = 0.010) were observed. Helminth-infected individuals had higher TIM-3 levels (adjusted β = 20.98, p = 0.020). The co-infected group had higher PD-1 (unadjusted β = 0.18, p = 0.0046) and PD-L2 (adjusted β = 7.95, p = 0.033) levels. A significant decrease in CD28 profile was observed across all infected groups: HIV-infected (adjusted β = −651.95, p = 0.010), helminth-infected (adjusted β = −674.32, p = 0.001), and co-infected (adjusted β = −671.55, p = 0.044). The results suggest that HIV-helminth co-infections alter immune checkpoint markers, potentially increasing cancer risk by promoting an immunosuppressive microenvironment that hinders anti-cancer immunity. CD28’s downregulation underscores immune inefficiency in chronic diseases. Addressing these co-infections is crucial for improving HIV care and potentially reducing cancer risks through targeted strategies. Full article

Leukemia is a hematologic malignancy; acute lymphoblastic leukemia (ALL) is the most prevalent subtype among children rather than in adults. Orthoherpesviridae family members produce proteins during latent infection phases that may contribute to cancer development. One such protein, viral interleukin-10 (vIL-10), closely resembles human interleukin-10 (IL-10) in structure. Research has explored the involvement of human cytomegalovirus (hCMV) in the pathogenesis of ALL. However, the limited characterization of its latent-phase proteins restricts a full understanding of the relationship between hCMV infection and leukemia progression. Studies have shown that hCMV induces an inflammatory response during infection, marked by the release of cytokines and chemokines. Inflammation may, therefore, play a role in how hCMV contributes to oncogenesis in pediatric ALL, possibly mediated by latent viral proteins. The classification of a virus as oncogenic is based on its alignment with cancer’s established hallmarks. Viruses can manipulate host cellular mechanisms, causing dysregulated cell proliferation, evasion of apoptosis, and genomic instability. These processes lead to mutations, chromosomal abnormalities, and chronic inflammation, all of which are vital for carcinogenesis. This study aims to investigate the role of vIL-10 during the latent phase of hCMV as a potential factor in leukemia development. Full article

Despite significant advancements in early diagnosis and treatment, breast cancer (BC) remains a major global health challenge. Ongoing research is essential to identify novel risk factors, implement innovative screening programs, and develop personalized treatment approaches. Among the various risk factors, infection with certain oncogenic viruses has emerged as a potential contributor to BC development. Increasing evidence suggests that bovine leukemia virus (BLV) may contribute to zoonotic infections in humans, with a potential role in BC initiation and progression. This review evaluates clinical and experimental data on BLV presence in both malignant and non-malignant breast tissues, exploring potential mechanisms through which BLV may access human breast tissue and contribute to carcinogenesis. Current data reveal a higher prevalence of BLV infection in BC tissues compared to non-tumor tissues, correlating with an increased risk of BC development. In this context, dairy and meat products from BLV-infected animals have been proposed as potential transmission sources. BLV-encoded proteins disrupt key oncogenic pathways, which support their possible role in breast carcinogenesis. However, the interpretation of these findings is limited by potential confounding factors such as genetic predisposition, environmental exposures, and dietary influences. Further research, including well-controlled epidemiological studies, longitudinal cohorts, and mechanistic investigations into BLV proteins in human breast cells, is necessary to determine its role in BC development. Full article

Breast cancer (BC) remains a significant global health challenge, highlighting the need for continued research into novel risk factors, diagnostic approaches, and personalized treatments. Among emerging risk factors, viral infections have been implicated as potential contributors to breast carcinogenesis and BC progression. Recent evidence suggests that specific oncogenic strains of human cytomegalovirus (HCMV) may have the capacity to transform human mammary epithelial cells. This review assesses clinical data regarding HCMV presence in both tumor and non-tumor breast tissues, examining the role of HCMV oncoproteins in BC development and progression. Current findings indicate a higher prevalence of HCMV infection in breast carcinomas compared to non-tumor tissues, associated with an elevated risk of BC. Additionally, the HCMV-driven breast carcinogenesis model proposed here suggests that HCMV oncoproteins may activate multiple oncogenic pathways, fostering cell proliferation, survival, and tumor development. A deeper understanding of the role of HCMV in BC could enhance risk stratification and support the creation of targeted therapeutic strategies. Full article

Kaposi’s Sarcoma Herpesvirus (KSHV) is the causative agent of several human diseases. There are few effective treatments available to treat infection and KSHV oncogenesis. Disrupting the KSHV infectious cycle would diminish the viral spread. The KSHV lytic phase and production of new virions require efficient copying and packaging of the KSHV genome. KSHV encodes its own lytic DNA replication machinery, including the processivity factor (PF-8), which presents itself as an attractive target for antiviral development. We characterized PF-8 at the single molecule level using transmission electron microscopy to identify key molecular interactions that mediate viral DNA replication initiation. Our results indicate that PF-8 forms oligomeric ring structures (tetramer, hexamer, and/or dodecamer) similar to the related Epstein–Barr virus processivity factor (BMRF1). Our DNA positional mapping revealed high-frequency binding locations of PF-8 within the lytic origin of replication (OriLyt). A multi-variable analysis of PF-8 DNA-binding activity with three mutant OriLyts provides new insights into the mechanisms that PF-8 associates with viral DNA and complexes to form multi-ring-like structures. Collectively, these data enhance the mechanistic understanding of the molecular interactions (protein–protein and protein-DNA) of an essential KSHV DNA replication protein. Full article

Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus and the etiological agent of several diseases. These include the malignancies Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD), as well as the inflammatory disorder KSHV inflammatory cytokine syndrome (KICS). The KSHV lifecycle is characterized by two phases: a default latent phase and a lytic replication cycle. During latency, the virus persists as an episome within host cells, expressing a limited subset of viral genes to evade immune surveillance while promoting cellular transformation. The lytic phase, triggered by various stimuli, results in the expression of the full viral genome, production of infectious virions, and modulation of the tumor microenvironment. Both phases of the KSHV lifecycle play crucial roles in driving viral pathogenesis, influencing oncogenesis and immune evasion. This review dives into the intricate world of the KSHV lifecycle, focusing on the molecular mechanisms that drive its latent and lytic phases, their roles in disease progression, and current therapeutic strategies. Full article

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease with a complex pathogenesis, primarily affecting women. SLE is associated with the presence of autoantibodies, chronic inflammation, and multi-organ dysfunction. Increasing evidence suggests that SLE is linked to a higher risk of malignancies, compared to the general population, though the mechanism behind this phenomenon remains unclear. Malignant tumors are the fourth most common cause of death in SLE patients. SLE is associated with an elevated risk of hematological cancers, as well as cancers of the lungs, thyroid, liver, and bile ducts. The aim of this paper is to review the latest literature on the pathogenesis, epidemiology, and risk factors for malignancies in SLE patients. The mechanisms of oncogenesis in SLE are still not fully understood, and the pathophysiology includes such risk factors as chronic inflammation, immune disorders, therapies used, overlap syndromes of connective tissue diseases, viral infections, and traditional cancer risk factors. Evaluating these factors and understanding the process of oncogenesis are crucial for prevention. Systemic lupus erythematosus may be an independent risk factor for the development of malignancies. It is important to raise awareness among SLE patients about the increased risk of malignancies. Further research is needed to establish guidelines for prevention, including screening recommendations. Full article