Merkel cell polyomavirus (MCPyV) is the causative agent of an aggressive skin tumor, Merkel cell carcinoma (MCC). The viral genome is integrated into the tumor genome and harbors nonsense mutations in the helicase domain of large T antigen (LTAg). However, the molecular mechanisms by which the viral genome gains the tumor-specific mutations remain to be elucidated. Focusing on host cytosine deaminases APOBEC3s (A3s), we find that A3A, A3B, or A3G introduces A3-specific mutations into episomal MCPyV genomes in MCPyV-replicating 293-derivative cells. Sequence analysis of MCPyV genomes retrieved from the NCBI database revealed a decrease of TpC dinucleotide, a preferred target for A3A and A3B, in the 3'-region of the LTAg-coding sequence. The viral DNA isolated from tumors contained mutated cytosines, with a remarkable bias toward TpC dinucleotide. Analysis of publicly available microarray data showed that expression of interferon-γ and cytotoxic T cell markers was positively correlated with A3A, A3B, and A3G levels in MCPyV-positive but not in MCPyV-negative tumors. Finally, interferon-γ treatment induced A3B and A3G expression in the MCPyV-positive MCC cell line, MS-1. These results suggest that the interferon-γ-A3B axis plays pivotal roles in evolutionally shaping MCPyV genomic sequences and in generating tumor-specific LTAg mutations during MCC carcinogenesis.

You may also like...
Latest tweets:
Breathing+ by Breathing Labs has passed peer review in a randomized controlled clinical trial that was recently published in SCI Q2 journal Pediatric Pulmonology. Research done by @bezmialem Full text is available in a link here: https://www.breathinglabs.com/clinical-trials/research-breathing-labs-and-nintendo-clinical-trial-is-published-in-journal-pediatric-pulmonology-sci-q2-impact-factor-3/?fbclid=IwAR2wNhSgurdbrrf3gzOOkHthgiWfXJ1x8RWvnMhkSo6fi33QPZEGzxzd6jM
BREAKING: @breathinglabs and @Nintendo clinical trial is published in journal Pediatric Pulmonology (SCI Q2, Impact Factor > 3), full text: https://breathinglabs.com/Nintendo%20&%20Breathing%20Labs%202022 #telemedicine #telehealth #mhealth
BREATHING VR: Lately we are sourcing this VR headset for use in Breathing VR application. It allows easiest installation of both breathing+ headset cable, and USB charging cables, which is essential in professional use: https://www.banggood.com/VR-SHINECON-G5-VR-Glasses-3D-Virtual-Reality-Glasses-VR-Headset-For-iPhone-XS-11Pro-Mi10-p-1679808.html?rmmds=myorder&cur_warehouse=CN
Update: Each purchase of Breathing+ will now include three machine washable mouthpieces. Previous buyers will be supplied with those by their country representatives but will have to cover shipping costs. Please be patient while we arrange distribution. https://www.breathinglabs.com/latest-news/announcement-breathing-mouthpieces-for-clinical-and-professional-use-are-now-available/
Update: We moved servers + relocated all our games to our servers, please be patient while google reviews all that (showing unsafe website atm). Use duckduckgo or non-chromium browsers to reach our pages in the meantime. Everything ok + new product addons coming out in a month!
Registration and all functionalities at http://breathinglabs.com (and in our iOS and Android games) are fixed and fully working. If you find any issues -> [email protected]
We are back in stock with Breathing+, currently searching for VR supplier, and setting up mass production for toys and tens stimulation + in November we will be signing up new erasmus traineeships, research projects, bilateral, FP(eu), and asia-pacific ->[email protected]
BREAKING: Nintendo Co. Ltd (Japan) is implementing Breathing Games by @breathinglabs in FDA approved clinical trial for children with bronchiectasis: https://clinicaltrials.gov/ct2/show/NCT04038892
Notice to b2b partners: we are running late with some minor upgrade-> briefly running out of stock -> retail and b2b sale is closed until early october. To get a list of partners with stock to sell contact us at [email protected] Thanks, we'll go strong again in winter 💪