Search Results (23)

Oncogene-induced senescence (OIS) is a form of cellular senescence triggered by oncogenic signaling and, potentially, by infection with oncogenic viruses. The role of senescence, along with its associated secretory phenotype, in the development of cervical cancer remains unclear. Additionally, the expression of the senescence-associated secretory phenotype (SASP) has not yet been explored in cervical premalignant lesions infected by the Human Papilloma Virus (HPV). This study aimed to investigate the expression of OIS and SASP markers in HPV-infected cervical precancerous lesions. We used a set of patient-derived precancerous (n = 32) and noncancerous (chronic cervicitis; n = 10) tissue samples to investigate the gene expression of several OIS (LMNB1, CDKN2A, CDKN2B, and CDKN1A), and SASP (IL1A, CCL2, TGFB1, CXCL8, and MMP9) biomarkers using qRT-PCR. OIS status was confirmed in precancerous lesions based on Lamin B1 downregulation by immunohistochemical staining. HPV status for all precancerous lesions was tested. Most of the noncancerous samples showed high Lamin B1 expression, however, precancerous lesions exhibited significant Lamin B1 downregulation (p < 0.001). Fifty-five percent of the precancerous samples were positive for HPV infection, with HPV-16 as the dominant genotype. Lamin B1 downregulation coincided with HPV E6 positive expression. CDKN2A and CDKN2B expression was higher in precancerous lesions compared to noncancerous tissue, while LMNB1 was downregulated. The SASP profile of premalignant lesions included elevated CXCL8 and TGFB1 and reduced IL1A, CCL2, and MMP9. this work shall provide an opportunity to further examine the role of OIS and the SASP in the process of malignant cervical transformation. Full article

Infectious agents, notably viruses, can cause or increase the risk of cancer occurrences. These agents often disrupt normal cellular functions, promote uncontrolled proliferation and growth, and trigger chronic inflammation, leading to cancer. Approximately 20% of all cancer cases in humans are associated with an infectious pathogen. The International Agency for Research on Cancer (IARC) recognizes seven viruses as direct oncogenic agents, including Epstein–Barr Virus (EBV), Kaposi’s Sarcoma-associated herpesvirus (KSHV), human T-cell leukemia virus type-1 (HTLV-1), human papilloma virus (HPV), hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus type 1 (HIV-1). Most viruses linked to increased cancer risk are typically transmitted through contact with contaminated body fluids and high-risk behaviors. The risk of infection can be reduced through vaccinations and routine testing, as well as recognizing and addressing risky behaviors and staying informed about public health concerns. Numerous strategies are currently in pre-clinical phases or undergoing clinical trials for targeting cancers driven by viral infections. Herein, we provide an overview of risk factors associated with increased cancer incidence in people living with HIV (PLWH) as well as other chronic viral infections, and contributing factors such as aging, toxicity from ART, coinfections, and comorbidities. Furthermore, we highlight both antibody- and cell-based strategies directed against virus-induced cancers while also emphasizing approaches aimed at discovering cures or achieving complete remission for affected individuals. Full article

This study aims to describe the natural history of and identify the risk factors associated with oral human papillomavirus (HPV) infections in an Australian Indigenous cohort. A longitudinal cohort study design, with baseline (2018), 12-month, and 24-month data obtained from Indigenous Australians aged 18+ years in South Australia, was performed. Face-to-face interviews were conducted, and saliva samples for HPV testing were collected at each time point. Basic descriptive analyses were conducted to calculate prevalence, incidence, persistence, clearance, and incidence proportions of any HPV infection. Multivariable logistic regression analyses with adjusted prevalence ratios (PRs) were conducted to identify risk factors associated with oral HPV infection. Among 993 participants with valid saliva samples, 44 HPV types were identified. The prevalence of infection with any oral HPV infection was 51.3%, high-risk HPV was 11%, and types implicated in Heck’s disease (HPV 13 or 32) was 37.4%. The incidence, persistence, and clearance of any and high-risk HPV infections were 30.7%, 11.8% and 33.3% vs. 9.3%, 2.8%, and 9%, respectively. Our findings indicate that the prevalence, incidence, and persistence of oral HPV infection in a large sample of Indigenous Australians were high, and clearance was low. Oral sex behaviours and recreational drug use were risk factors associated with incident high-risk HPV infection. Full article

Interaction between infectious agents and liver tissue, as well as repeated and extreme biological events beyond adaptive capacities, may result in pathological conditions predisposing people to development of primary liver cancers (PLCs). In adults, PLCs mainly comprise hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Various infectious agents in the hepatic microenvironment can destabilize normal liver cell functions by modulating the Wnt/β-catenin pathway components. Among them, hepatotropic viruses B, C, and D are involved in Wnt/β-catenin signaling dysregulation. Other microbial agents, including oncogenic viruses such as Epstein–Barr virus (EBV) and human papilloma virus (HPV), bacteria, e.g., Mycoplasma hyorhinis and Salmonella Typhi, the protozoan parasite Toxoplasma gondii, the fungus Aspergillus flavus, and liver flukes such as Clonorchissinensis or Opisthorchis viverrini, may induce malignant transformation in hepatocytes or in target cells of the biliary tract through aberrant Wnt signaling activation. This review focuses on new insights into infectious agents implicated in the deregulation of Wnt signaling and PLC development. Since the Wnt/β-catenin pathway is a driver of cancer following viral and bacterial infections, molecules inhibiting the complex axis of Wnt signaling could represent novel therapeutic approaches in PLC treatment. Full article

Vaginal dysbiosis is characterized by a decrease in the relative abundance of Lactobacillus species in favor of other species. This condition facilitates infections by sexually transmitted pathogens including high risk (HR)-human papilloma viruses (HPVs) involved in the development of cervical cancer. Some vaginal dysbiosis bacteria contribute to the neoplastic progression by inducing chronic inflammation and directly activating molecular pathways involved in carcinogenesis. In this study, SiHa cells, an HPV-16-transformed epithelial cell line, were exposed to different representative vaginal microbial communities. The expression of the HPV oncogenes E6 and E7 and the production of relative oncoproteins was evaluated. The results showed that Lactobacillus crispatus and Lactobacillus gasseri modulated the basal expression of the E6 and E7 genes of SiHa cells and the production of the E6 and E7 oncoproteins. Vaginal dysbiosis bacteria had contrasting effects on E6/E7 gene expression and protein production. The expression of the E6 and E7 genes and the production of the relative oncoproteins was increased by strains of Gardnerella vaginalis and, to a lesser extent, by Megasphaera micronuciformis. In contrast, Prevotella bivia decreased the expression of oncogenes and the production of the E7 protein. A decreased amount of p53 and pRb was found in the cultures of SiHa cells with M. micronuciformis, and accordingly, in the same cultures, a higher percentage of cells progressed to the S-phase of the cell cycle compared to the untreated or Lactobacillus-stimulated cultures. These data confirm that L. crispatus represents the most protective component of the vaginal microbiota against neoplastic progression of HR-HPV infected cells, while M. micronuciformis and, to a lesser extent, G. vaginalis may directly interfere in the oncogenic process, inducing or maintaining the production of viral oncoproteins. Full article

Senescence represents a unique cellular stress response characterized by a stable growth arrest, macromolecular alterations, and wide spectrum changes in gene expression. Classically, senescence is the end-product of progressive telomeric attrition resulting from the repetitive division of somatic cells. In addition, senescent cells accumulate in premalignant lesions, in part, as a product of oncogene hyperactivation, reflecting one element of the tumor suppressive function of senescence. Oncogenic processes that induce senescence include overexpression/hyperactivation of H-Ras, B-Raf, and cyclin E as well as inactivation of PTEN. Oncogenic viruses, such as Human Papilloma Virus (HPV), have also been shown to induce senescence. High-risk strains of HPV drive the immortalization, and hence transformation, of cervical epithelial cells via several mechanisms, but primarily via deregulation of the cell cycle, and possibly, by facilitating escape from senescence. Despite the wide and successful utilization of HPV vaccines in reducing the incidence of cervical cancer, this measure is not effective in preventing cancer development in individuals already positive for HPV. Accordingly, in this commentary, we focus on the potential contribution of oncogene and HPV-induced senescence (OIS) in cervical cancer. We further consider the potential utility of senolytic agents for the elimination of HPV-harboring senescent cells as a strategy for reducing HPV-driven transformation and the risk of cervical cancer development. Full article

Viruses are dependent on host factors in order to efficiently establish an infection and replicate. Targeting the interactions of such host factors provides an attractive strategy to develop novel antivirals. Syntenin is a protein known to regulate the architecture of cellular membranes by its involvement in protein trafficking and has previously been shown to be important for human papilloma virus (HPV) infection. Here, we show that a highly potent and metabolically stable peptide inhibitor that binds to the PDZ1 domain of syntenin inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by blocking the endosomal entry of the virus. Furthermore, we found that the inhibitor also hampered chikungunya infection and strongly reduced flavivirus infection, which is completely dependent on receptor-mediated endocytosis for their entry. In conclusion, we have identified a novel broad spectrum antiviral inhibitor that efficiently targets a broad range of RNA viruses. Full article

Human papillomaviruses (HPV) are a large group of DNA viruses that infect the basal cells of the stratified epithelium at different anatomic locations. In the ocular adnexal region, the mucosa of the conjunctiva and the lacrimal drainage system, as well as the eyelid skin, are potential locations for HPV-related neoplasia. The role of HPV in squamous cell neoplasia of the ocular adnexa has been debated for several decades. Due to the rarity of all these tumors, large studies are not available in the scientific literature, thereby hampering the precision of the HPV prevalence estimates and the ability to conclude. Nevertheless, increasing evidence supports that defined subsets of conjunctival papillomas, intraepithelial neoplasia, and carcinomas develop in an HPV-dependent pathway. The role of HPV in squamous cell tumors arising in the lacrimal drainage system and the eyelid is still uncertain. Further, the potential of HPV status as a diagnostic, prognostic, or predictive biomarker in these diseases is a topic for future research. Full article

Persistent infection with High Risk-Human Papilloma Viruses (HR-HPVs) is a primary cause of cervical cancer worldwide. Vaginal-dysbiosis-associated bacteria were correlated with the persistence of HR-HPVs infection and with increased cancer risk. We obtained strains of the most represented bacterial species in vaginal microbiota and evaluated their effects on the survival of cervical epithelial cells and immune homeostasis. The contribution of each species to supporting the antiviral response was also studied. Epithelial cell viability was affected by culture supernatants of most vaginal-dysbiosis bacteria, whereas Lactobacillus gasseri or Lactobacillus jensenii resulted in the best stimulus to induce interferon-γ (IFN-γ) production by human mononuclear cells from peripheral blood (PBMCs). Although vaginal-dysbiosis-associated bacteria induced the IFN-γ production, they were also optimal stimuli to interleukin-17 (IL-17) production. A positive correlation between IL-17 and IFN-γ secretion was observed in cultures of PBMCs with all vaginal-dysbiosis-associated bacteria suggesting that the adaptive immune response induced by these strains is not dominated by T_H1 differentiation with reduced availability of IFN-γ, cytokine most effective in supporting virus clearance. Based on these results, we suggest that a vaginal microbiota dominated by lactobacilli, especially by L. gasseri or L. jensenii, may be able to assist immune cells with clearing HPV infection, bypasses the viral escape and restores immune homeostasis. Full article

Cancer arises from the accumulation of genetic and epigenetic alterations. Even in the era of precision oncology, carcinogens contributing to neoplastic process are still an important focus of research. Comprehensive genomic analyses have revealed various combinations of base substitutions, referred to as the mutational signatures, in cancer. Each mutational signature is believed to arise from specific DNA damage and repair processes, including carcinogens. However, as a type of carcinogen, tumor viruses increase the cancer risk by alternative mechanisms, including insertional mutagenesis, viral oncogenes, and immunosuppression. In this review, we summarize virus-driven carcinogenesis to provide a framework for the control of malignant cell proliferation. We first provide a brief overview of oncogenic viruses and describe their implication in virus-related tumors. Next, we describe tumor viruses (HPV, Human papilloma virus; HBV, Hepatitis B virus; HCV, Hepatitis C virus; EBV, Epstein–Barr virus; Kaposi sarcoma herpesvirus; MCV, Merkel cell polyoma virus; HTLV-1, Human T-cell lymphotropic virus, type-1) and tumor virus-related cancers. Lastly, we introduce emerging tumor virus candidates, human cytomegalovirus (CMV), human herpesvirus-6 (HHV-6) and adeno-associated virus-2 (AAV-2). We expect this review to be a hub in a complex network of data for virus-associated carcinogenesis. Full article

Viruses are infectious agents that hijack the host cell machinery in order to replicate and generate progeny. Viral infection is initiated by attachment to host cell receptors, and typical viral receptors are cell-surface-borne molecules such as proteins or glycan structures. Sialylated glycans (glycans bearing sialic acids) and glycosaminoglycans (GAGs) represent major classes of carbohydrate receptors and have been implicated in facilitating viral entry for many viruses. As interactions between viruses and sialic acids have been extensively reviewed in the past, this review provides an overview of the current state of structural knowledge about interactions between non-enveloped human viruses and GAGs. We focus here on adeno-associated viruses, human papilloma viruses (HPVs), and polyomaviruses, as at least some structural information about the interactions of these viruses with GAGs is available. We also discuss the multivalent potential for GAG binding, highlighting the importance of charged interactions and positively charged amino acids at the binding sites, and point out challenges that remain in the field. Full article

Infections that are triggered by the accompanying immunosuppression in patients with burn wounds are very common regardless of age. Among burn patients, the most frequently diagnosed infections include the bacterial ones primarily caused by Pseudomonas aeruginosa or Klebsiella pneumonia, as well as fungal infections with the etiology of Candida spp. or Aspergillus spp. Besides, burn wounds are highly susceptible to viral infections mainly due to the impaired immune responses and defective functions of the immune cells within the wound microenvironment. The most prevalent viruses that invade burn wounds include herpes simplex virus (HSV), cytomegalovirus (CMV), human papilloma virus (HPV), and varicella zoster virus (VZV). Likewise, less prevalent infections such as those caused by the orf virus or Epstein–Barr Virus (EBV) might also occur in immunosuppressed burn patients. Viral infections result in increased morbidity and mortality rates in severely burned patients. Additionally, a positive correlation between the hospitalization duration and the severity of the viral infection has been demonstrated. Viral infections trigger the occurrence of various complications, ranging from mild symptoms to even fatal incidents. Accurate detection of viral infection is of great clinical importance because of the possibility for a quicker introduction of proper treatment therapy and shortening of hospitalization time. The aim of this paper is to provide a comprehensive review of the literature and summarize the findings regarding the most common viral infections in immunosuppressed burn patients. Full article

Vaccination is arguably the most cost-effective preventative measure against infectious diseases. While vaccines have been successfully developed against certain viruses (e.g., yellow fever virus, polio virus, and human papilloma virus HPV), those against a number of other important public health threats, such as HIV-1, hepatitis C, and respiratory syncytial virus (RSV), have so far had very limited success. The global pandemic of COVID-19, caused by the SARS-CoV-2 virus, highlights the urgency of vaccine development against this and other constant threats of zoonotic infection. While some traditional methods of producing vaccines have proven to be successful, new concepts have emerged in recent years to produce more cost-effective and less time-consuming vaccines that rely on viral vectors to deliver the desired immunogens. This review discusses the advantages and disadvantages of different viral vaccine vectors and their general strategies and applications in both human and veterinary medicines. A careful review of these issues is necessary as they can provide important insights into how some of these viral vaccine vectors can induce robust and long-lasting immune responses in order to provide protective efficacy against a variety of infectious disease threats to humans and animals, including those with zoonotic potential to cause global pandemics. Full article

Recent reports have pointed to the link between persistent inflammation, oxidative stress, and carcinogenesis; however most of the studies concerning the role of viruses in head and neck cancer (HNC) are focused mainly on one type of virus. Our present study aimed to study the relationship between Epstein–Barr virus/human papilloma virus (EBV/HPV) coinfection and glutathione peroxidase (GPx) and superoxide dismutase (SOD) level in oropharyngeal cancer. Fresh-frozen tumor tissue samples were collected from 128 patients with oropharyngeal cancer infected with EBV or HPV or with EBV/HPV coinfection. After DNA extraction, EBV and HPV DNA was detected using a polymerase chain reaction (PCR) assay. GPx and SOD activity was determined in homogenates of cancer tissue using diagnostic kits produced by Randox Laboratories. Both GPx and SOD activity was statistically lower in patients with EBV/HPV coinfection than in a single EBV or HPV infection. Analysis of GPx and SOD activity in relation to histological grading and tumor, node (TN) classification revealed that in poorly-differentiated tumors, the level of antioxidant enzymes was lower compared with well-differentiated lesions and in cases with greater tumor dimensions and lymph-node involvement, both GPx and SOD activity was decreased. Further studies are necessary to clarify the influence of interplay between EBV, HPV, and oxidative stress on malignant transformation of upper aerodigestive tract epithelial cells. Full article

Recent developments in bioinformatics technologies have led to advances in our understanding of how oncogenic viruses such as the human papilloma virus drive cancer progression and evade the host immune system. Here, we focus our review on understanding how these emerging bioinformatics technologies influence our understanding of how human papilloma virus (HPV) drives immune escape in cancers of the head and neck, and how these new informatics approaches may be generally applicable to other virally driven cancers. Indeed, these tools enable researchers to put existing data from genome wide association studies, in which high risk alleles have been identified, in the context of our current understanding of cellular processes regulating neoantigen presentation. In the future, these new bioinformatics approaches are highly likely to influence precision medicine-based decision making for the use of immunotherapies in virally driven cancers. Full article