Abstract
Oncoviruses, known as cancer-causing viruses, are typically involved in cancer progression by inhibiting tumor suppressor pathways and uncontrolled cell division. Myeloid cells are the most ...frequent populations recruited to the tumor microenvironment (TME) and play a critical role in cancer development and metastasis of malignant tumors. Tumor-infiltrating myeloid cells, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), tumor-associated dendritic cells (TADCs), and tumor-associated neutrophils (TANs) exert different states from anti-tumorigenic to pro-tumorigenic phenotypes in TME. Although their role in the anti-tumorigenic state is well introduced, their opposing roles, pro-tumorigenic activities, such as anti-inflammatory cytokine and reactive oxygen species (ROS) production, should not be ignored since they result in inflammation, tumor progression, angiogenesis, and evasion. Since the blockade of these cells had promising results against cancer progression, their inhibition might be helpful in various cancer immunotherapies. This review highlights the promoting role of tumor-associated myeloid cells (TAMCs) in the pathophysiology of human virus tumorigenesis.
It is evidenced that 20% of all tumors in humans are caused by oncoviruses, including human papilloma viruses, Epstein‐Barr virus, Kaposi sarcoma virus, human polyomaviruses, human T‐lymphotrophic ...virus‐1, and hepatitis B and C viruses. Human immunodeficiency virus is also involved in carcinogenesis, although not directly, but by facilitating the infection of many oncoviruses through compromising the immune system. Being intracellular parasites with the property of establishing latency and integrating into the host genome, these viruses are a therapeutic challenge for biomedical researchers. Therefore, strategies able to target nucleotide sequences within episomal or integrated viral genomes are of prime importance in antiviral or anticancerous armamentarium. Recently, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) has emerged as a powerful genome editing tool. Standing out as a precise and efficient oncoviruses method, it has been extensively applied in recent experimental ventures in the field of molecular medicine, particularly in combating infections including tumor inducing viruses. This review is aimed at collating the experimental and clinical advances in CRISPR/Cas9 technology in terms of its applications against oncoviruses. Primarily, it will focus on the application of CRISPR/Cas9 in combating tumor viruses, types of mechanisms targeted, and the significant outcomes till date. The technical pitfalls of the CRISPR/Cas9 and the comparative approaches in evaluating this technique with respect to other available alternatives are also described briefly. Furthermore, the review also discussed the clinical aspects and the ethical, legal, and social issues associated with the use of CRISPR/Cas9.
Approximately 15-20% of global cancer cases are attributed to virus infections. Oncoviruses employ various molecular strategies to enhance replication and persistence. Human cytomegalovirus (HCMV), ...acting as an initiator or promoter, enables immune evasion, supporting tumor growth. HCMV activates pro-oncogenic pathways within infected cells and direct cellular transformation. Thus, HCMV demonstrates characteristics reminiscent of oncoviruses. Cumulative evidence emphasizes the crucial roles of EZH2 and Myc in oncogenesis and stemness. EZH2 and Myc, pivotal regulators of cellular processes, gain significance in the context of oncoviruses and HCMV infections. This axis becomes a central focus for comprehending the mechanisms driving virus-induced oncogenesis. Elevated EZH2 expression is evident in various cancers, making it a prospective target for cancer therapy. On the other hand, Myc, deregulated in over 50% of human cancers, serves as a potent transcription factor governing cellular processes and contributing to tumorigenesis; Myc activates EZH2 expression and induces global gene expression. The Myc/EZH2 axis plays a critical role in promoting tumor growth in oncoviruses. Considering that HCMV has been shown to manipulate the Myc/EZH2 axis, there is emerging evidence suggesting that HCMV could be regarded as a potential oncovirus due to its ability to exploit this critical pathway implicated in tumorigenesis.
High-throughput sequencing (HTS) has revolutionised the field of pathogen genomics, enabling the direct recovery of pathogen genomes from clinical and environmental samples. However, pathogen nucleic ...acids are often overwhelmed by those of the host, requiring deep metagenomic sequencing to recover sufficient sequences for downstream analyses (e.g., identification and genome characterisation). To circumvent this, hybrid-capture target enrichment (HC) is able to enrich pathogen nucleic acids across multiple scales of divergences and taxa, depending on the panel used. In this review, we outline the applications of HC in human pathogens-bacteria, fungi, parasites and viruses-including identification, genomic epidemiology, antimicrobial resistance genotyping, and evolution. Importantly, we explored the applicability of HC to clinical metagenomics, which ultimately requires more work before it is a reliable and accurate tool for clinical diagnosis. Relatedly, the utility of HC was exemplified by COVID-19, which was used as a case study to illustrate the maturity of HC for recovering pathogen sequences. As we unravel the origins of COVID-19, zoonoses remain more relevant than ever. Therefore, the role of HC in biosurveillance studies is also highlighted in this review, which is critical in preparing us for the next pandemic. We also found that while HC is a popular tool to study viruses, it remains underutilised in parasites and fungi and, to a lesser extent, bacteria. Finally, weevaluated the future of HC with respect to bait design in the eukaryotic groups and the prospect of combining HC with long-read HTS.
The study of tumor viruses paves the way for understanding the mechanisms of virus pathogenesis, including those involved in establishing infection and dissemination in the host tumor affecting ...immune-compromised patients. The processes ranging from viral infection to progressing malignancy are slow and usually insufficient for establishment of transformed cells that develop cancer in only a minority of infected subjects. Therefore, viral infection is usually not the only cause of cancer, and further environmental and host factors, may be implicated. HTLV-I, in particular, is considered as an oncovirus cause of lymphoproliferative disease such as adult T cell leukemia/lymphoma (ATL) and disturbs the immune responses which results in HTLV-I associated meylopathy/tropical spastic parapresis (HAM/TSP). HTLV-I infection causes ATL in a small proportion of infected subjects (2-5%) following a prolonged incubation period (15-30 years) despite a strong adaptive immune response against the virus. Overall, these conditions offer a prospect to study the molecular basis of tumorgenicity in mammalian cells. In this review, the oncogencity of HTLV-I is being considered as an oncovirus in context of ATL.
Global cancer incidence and mortality are on the rise. Although cancer is fundamentally a non-communicable disease, a large number of cancers are known to have a viral aetiology. A high burden of ...infectious agents (Human immunodeficiency virus (HIV), human papillomavirus (HPV), hepatitis B virus (HBV)) in certain Sub-Saharan African countries drives the rates of certain cancers. About one-third of all cancers in Africa are attributed to infection. Seven viruses have been identified with carcinogenic characteristics, namely the HPV, HBV, Hepatitis C virus (HCV), Epstein-Barr virus (EBV), Human T cell leukaemia virus 1 (HTLV-1), Kaposi's Sarcoma Herpesvirus (KSHV), and HIV-1. The cellular splicing machinery is compromised upon infection, and the virus generates splicing variants that promote cell proliferation, suppress signalling pathways, inhibition of tumour suppressors, alter gene expression through epigenetic modification, and mechanisms to evade an immune response, promoting carcinogenesis. A number of these splice variants are specific to virally-induced cancers. Elucidating mechanisms underlying how the virus utilises these splice variants to maintain its latent and lytic phase will provide insights into novel targets for drug discovery. This review will focus on the splicing genomics, epigenetic modifications induced by and current therapeutic strategies against HPV, HBV, HCV, EBV, HTLV-1, KSHV and HIV-1.
Common Variable Immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disorder characterised by impaired antibody production, leading to recurrent infections and an increased ...susceptibility to viral pathogens. This literature review aims to provide a comprehensive overview of CVID's relationship with viral infections, encompassing disease pathogenesis, key presenting features, specific monogenic susceptibilities, the impact of COVID-19, and existing treatment options. The pathogenesis of CVID involves complex immunological dysregulation, including defects in B cell development, antibody class switching, and plasma cell differentiation. These abnormalities contribute to an impaired humoral immune response against viral agents, predisposing individuals with CVID to a broad range of viral infections. Genetic factors play a prominent role in CVID, and monogenic drivers of CVID-like disease are increasingly identified through advanced genomic studies. Some monogenic causes of the CVID-like phenotype appear to cause specific viral susceptibilities, and these are explored in the review. The emergence of the COVID-19 pandemic highlighted CVID patients' heightened predisposition to severe outcomes with viral infections. This review explores the clinical manifestations, outcomes, and potential therapeutic approaches for COVID-19 in CVID patients. It assesses the efficacy of prophylactic measures for COVID-19, including vaccination and immunoglobulin replacement therapy, as well as trialled therapies.
About 15-20% of human cancers worldwide have viral etiology. Seven human DNA and RNA viruses are accepted to be oncogenic viruses or oncoviruses and contribute to the development of various cancer ...types. Human oncoviruses have developed multiple molecular mechanisms to interfere with specific cellular pathways to promote viral replication and viral life cycle maintenance in the host. Despite the diversity of oncogenic viruses, they use similar strategies for cancer development. Viral oncoproteins and viral non-coding RNAs are the key factors that can affect multiple cellular processes on both genetic and epigenetic levels. Epigenetics research allows better understanding of the complex interplay between oncoviruses and the host cells. This review highlights the importance of epigenetic reprogramming for virus-induced carcinogenesis. Recent progress in the development of pharmacological tools for targeting epigenetic mechanisms opens new perspectives for modulation of virus/host interaction and intervention of virus-induced cancer. Several clinical trials have been carried out or are on-going involving epigenetic drugs not only as single therapeutic but also in combination with other targeted agents against various virus-induced cancers.
Human herpesviruses (HHVs) and human papillomavirus (HPV) are common in the general population and, in immunocompetent people, are mostly carried asymptomatically. However, once an individual becomes ...immunocompromised by age, illness or HIV infection these dormant viruses can manifest and produce disease. In HIV‐positive patients, there is an increased risk of disease caused by HHVs and HPV infections and cancers caused by the oncoviruses Epstein–Barr Virus, HHV‐8 and HPV. This workshop examined four questions regarding the viruses associated with oral cancers and disease in the HIV‐positive and ‐negative populations, the immune response, and biomarkers useful for accurate diagnostics of these infections and their sequalae. Each presenter identified a number of key areas where further research is required.
Viral Noncoding RNAs in Cancer Biology Li, Zhi; Fu, Shujun; Sun, Lun-Quan
Advances in experimental medicine and biology,
01/2016, Letnik:
927
Journal Article
Recenzirano
Over 12 % of all human cancers are caused by oncoviruses, primarily including Epstein-Barr virus (EBV), high-risk human papillomaviruses (HPVs), hepatitis B and C viruses (HBV and HCV, respectively), ...and Kaposi's sarcoma herpesvirus (KSHV). In addition to viral oncoproteins, a variety of noncoding RNAs (ncRNAs) produced by oncoviruses have been recognized as important cofactors that contribute to the oncogenic events. In this chapter, we will focus on the recent understanding of the long and short noncoding RNAs, as well as microRNAs of the viruses, and discuss their roles in the biology of multistep oncogenesis mediated by established human oncoviruses.
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