Background: Although the role of viral agents, such as human papillomavirus (e.g. HPV16, HPV18) in colorectal cancer (CRC) has been previously investigated, results remain inconclusive.
View Article and Find Full Text PDFHere, we demonstrate that the direct binding of p53 on the IL-18 promoter region regulates its gene expression. However, the presence of E6 and E7 from human papillomavirus type 38 impairs this mechanism via a new inhibitory complex formed by DNA methyltransferase 1 (DNMT1)/PKR/ΔNp73α, which binds to the region formerly occupied by p53 in primary keratinocytes.
View Article and Find Full Text PDFTumor suppressor p53 and its related proteins, p63 and p73, can be synthesized as multiple isoforms lacking part of the N- or C-terminal regions. Specifically, high expression of the ΔNp73α isoform is notoriously associated with various human malignancies characterized by poor prognosis. This isoform is also accumulated by oncogenic viruses, such as Epstein-Barr virus (EBV), as well as genus beta human papillomaviruses (HPV) that appear to be involved in carcinogenesis.
View Article and Find Full Text PDFWe here investigate the impact of antiviral treatments such as remdesivir on intra-host genomic diversity and emergence of SARS-CoV2 variants in patients with a prolonged course of infection. Sequencing and variant analysis performed in 112 longitudinal respiratory samples from 14 SARS-CoV2-infected patients with severe disease progression show that major frequency variants do not generally arise during prolonged infection. However, remdesivir treatment can increase intra-host genomic diversity and result in the emergence of novel major variant species harboring fixed mutations.
View Article and Find Full Text PDFBackground: The recent emergence of distinct and highly successful SARS-CoV-2 lineages has substantial implications for individual patients and public health measures. While next-generation-sequencing is routinely performed for surveillance purposes, RT-qPCR can be used to rapidly rule-in or rule-out relevant variants, e.g.
View Article and Find Full Text PDFBackground: The MinION sequencer belongs to the third generation of sequencing technology that allows for the generation of ultra-long reads, representing a potentially more effective approach to characterize entire viral genome sequences than other time-consuming and low-throughput methodologies.
Methods: We report the use of the MinION nanopore sequencer to sequence the full-length genome of human papillomavirus (HPV)-ICB2 (7441 bp), which was previously characterized in our laboratory. Three independent MinION libraries were prepared and sequenced using either three consecutive 12 -h runs (Protocol A) or a single run of 48 h starting from a pool of three barcoded DNA libraries (Protocol B).
So far, only a few reports about reinfections with SARS-CoV-2 have been published, and they often lack detailed immunological and virological data. We report about a SARS-CoV-2 reinfection with a genetically distinct SARS-CoV-2 variant in an immunocompetent female healthcare worker that has led to a mild disease course. No obvious viral escape mutations were observed in the second virus variant.
View Article and Find Full Text PDFBackground: To characterize the HPV diversity in the anal mucosa of men with different sexual behavior and HIV status by next-generation sequencing (NGS).
Methods: Anal swabs from HIV-positive (n = 94; mean age, 38 years) and HIV-negative (n = 100; mean age, 37.5 years) men who have sex with men (MSM) and HIV-negative men (predominantly men who have sex with women, MSW) (n = 99; mean age, 38.
We describe a multifactorial investigation of a SARS-CoV-2 outbreak in a large meat processing complex in Germany. Infection event timing, spatial, climate and ventilation conditions in the processing plant, sharing of living quarters and transport, and viral genome sequences were analyzed. Our results suggest that a single index case transmitted SARS-CoV-2 to co-workers over distances of more than 8 m, within a confined work area in which air is constantly recirculated and cooled.
View Article and Find Full Text PDFBoth mucosal and cutaneous Human Papillomaviruses (HPVs) can be detected in the oral cavity, but investigations regarding the epidemiology of cutaneous HPVs at this site are scarce. We assessed mucosal (alpha) and cutaneous (beta and gamma) HPV infection in oral samples of HIV-infected and uninfected men who have sex with men (MSM). Oral rinse-and-gargles were collected from 310 MSM.
View Article and Find Full Text PDFTumor suppressors can exert pro-proliferation functions in specific contexts. In the beta human papillomavirus type 38 (HPV38) experimental model, the viral proteins E6 and E7 promote accumulation of a wild-type (WT) p53 form in human keratinocytes (HKs), promoting cellular proliferation. Inactivation of p53 by different means strongly decreases the proliferation of HPV38 E6/E7 HKs.
View Article and Find Full Text PDFThe beta human papillomaviruses (HPVs) are subdivided into 5 species (beta-1 to beta-5), and they were first identified in the skin. However, the beta-3 species appears to be more highly represented in the mucosal epithelia than in the skin. Functional studies have also highlighted that beta-3 HPV49 shares some functional similarities with mucosal high-risk (HR) HPV16.
View Article and Find Full Text PDFBackground: The detection of known human papillomaviruses (PVs) from targeted wet-lab approaches has traditionally used PCR-based methods coupled with Sanger sequencing. With the introduction of next-generation sequencing (NGS), these approaches can be revisited to integrate the sequencing power of NGS. Although computational tools have been developed for metagenomic approaches to search for known or novel viruses in NGS data, no appropriate tool is available for the classification and identification of novel viral sequences from data produced by amplicon-based methods.
View Article and Find Full Text PDFActinic keratosis (AK) arises on photo-damaged skin and is considered to be the precursor lesion of cutaneous squamous cell carcinoma (cSCC). Many findings support the involvement of β human papillomaviruses (HPVs) in cSCC, while very little is known on γ HPV types. The objective of this study was to characterize the spectrum of PV types in healthy skin (HS) and AK samples of the same immunocompetent individuals using next generation sequencing (NGS).
View Article and Find Full Text PDFMerkel cell polyomavirus (MCPyV) is the first human polyomavirus etiologically associated with Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer. Similar to other polyomaviruses, MCPyV encodes early T antigen genes, viral oncogenes required for MCC tumor growth. To identify the unique oncogenic properties of MCPyV, we analyzed the gene expression profiles in human spontaneously immortalized keratinocytes (NIKs) expressing the early genes from six distinct human polyomaviruses (PyVs), including MCPyV.
View Article and Find Full Text PDFWe have previously showed that a transgenic (Tg) mouse model with cytokeratin 14 promoter (K14)-driven expression of E6 and E7 from beta-3 HPV49 in the basal layer of the epidermis and of the mucosal epithelia of the digestive tract (K14 HPV49 E6/E7 Tg mice) are highly susceptible to upper digestive tract carcinogenesis upon exposure to 4-nitroquinoline 1-oxide (4NQO). Using whole-exome sequencing, we show that in K14 HPV49 E6/E7 Tg mice, development of 4NQO-induced cancers tightly correlates with the accumulation of somatic mutations in cancer-related genes. The mutational signature in 4NQO-treated mice was similar to the signature observed in humans exposed to tobacco smoking and tobacco chewing.
View Article and Find Full Text PDFWe present a new database, specifically devoted to ROS homeostasis regulated proteins. This database replaced our previous database, the PeroxiBase, which was focused only on various peroxidase families. The addition of 20 new protein families related with ROS homeostasis justifies the new name for this more complex and comprehensive database as RedoxiBase.
View Article and Find Full Text PDFThe histone modifier lysine (K)-specific demethylase 2B (KDM2B) plays a role in the differentiation of hematopoietic cells, and its expression appears to be deregulated in certain cancers of hematological and lymphoid origins. We have previously found that the gene is differentially methylated in cell lines derived from Epstein-Barr virus (EBV)-associated endemic Burkitt lymphoma (eBL) compared with that in EBV-negative sporadic Burkitt lymphoma-derived cells. However, whether KDM2B plays a role in eBL development has not been previously investigated.
View Article and Find Full Text PDFHumans are frequently exposed to acrylamide, a probable human carcinogen found in commonplace sources such as most heated starchy foods or tobacco smoke. Prior evidence has shown that acrylamide causes cancer in rodents, yet epidemiological studies conducted to date are limited and, thus far, have yielded inconclusive data on association of human cancers with acrylamide exposure. In this study, we experimentally identify a novel and unique mutational signature imprinted by acrylamide through the effects of its reactive metabolite glycidamide.
View Article and Find Full Text PDFWe report the complete genome characterization of a novel human papillomavirus (HPV) (ICB2) isolated from a skin swab. The L1 region of HPV ICB2 shares 87.9% nucleotide similarity with its closest relative, HPV37, and thus constitutes a novel human betapapillomavirus.
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