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Presence of complete murine viral genome sequences in patient-derived xenografts

Patient-derived xenografts are crucial for drug development but their use is challenged by issues such as murine viral infection. We evaluate the scope of viral infection and its impact on patient-derived xenografts by taking an unbiased data-driven approach to analyze unmapped RNA-Seq reads from 18...

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Autores principales: Yuan, Zihao, Fan, Xuejun, Zhu, Jay-Jiguang, Fu, Tong-Ming, Wu, Jiaqian, Xu, Hua, Zhang, Ningyan, An, Zhiqiang, Zheng, W. Jim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017013/
https://www.ncbi.nlm.nih.gov/pubmed/33795676
http://dx.doi.org/10.1038/s41467-021-22200-5
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author Yuan, Zihao
Fan, Xuejun
Zhu, Jay-Jiguang
Fu, Tong-Ming
Wu, Jiaqian
Xu, Hua
Zhang, Ningyan
An, Zhiqiang
Zheng, W. Jim
author_facet Yuan, Zihao
Fan, Xuejun
Zhu, Jay-Jiguang
Fu, Tong-Ming
Wu, Jiaqian
Xu, Hua
Zhang, Ningyan
An, Zhiqiang
Zheng, W. Jim
author_sort Yuan, Zihao
collection PubMed
description Patient-derived xenografts are crucial for drug development but their use is challenged by issues such as murine viral infection. We evaluate the scope of viral infection and its impact on patient-derived xenografts by taking an unbiased data-driven approach to analyze unmapped RNA-Seq reads from 184 experiments. We find and experimentally validate the extensive presence of murine viral sequence reads covering entire viral genomes in patient-derived xenografts. The existence of viral sequences inside tumor cells is further confirmed by single cell sequencing data. Extensive chimeric reads containing both viral and human sequences are also observed. Furthermore, we find significantly changed expression levels of many cancer-, immune-, and drug metabolism-related genes in samples with high virus load. Our analyses indicate a need to carefully evaluate the impact of viral infection on patient-derived xenografts for drug development. They also point to a need for attention to quality control of patient-derived xenograft experiments.
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spelling pubmed-80170132021-04-16 Presence of complete murine viral genome sequences in patient-derived xenografts Yuan, Zihao Fan, Xuejun Zhu, Jay-Jiguang Fu, Tong-Ming Wu, Jiaqian Xu, Hua Zhang, Ningyan An, Zhiqiang Zheng, W. Jim Nat Commun Article Patient-derived xenografts are crucial for drug development but their use is challenged by issues such as murine viral infection. We evaluate the scope of viral infection and its impact on patient-derived xenografts by taking an unbiased data-driven approach to analyze unmapped RNA-Seq reads from 184 experiments. We find and experimentally validate the extensive presence of murine viral sequence reads covering entire viral genomes in patient-derived xenografts. The existence of viral sequences inside tumor cells is further confirmed by single cell sequencing data. Extensive chimeric reads containing both viral and human sequences are also observed. Furthermore, we find significantly changed expression levels of many cancer-, immune-, and drug metabolism-related genes in samples with high virus load. Our analyses indicate a need to carefully evaluate the impact of viral infection on patient-derived xenografts for drug development. They also point to a need for attention to quality control of patient-derived xenograft experiments. Nature Publishing Group UK 2021-04-01 /pmc/articles/PMC8017013/ /pubmed/33795676 http://dx.doi.org/10.1038/s41467-021-22200-5 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yuan, Zihao
Fan, Xuejun
Zhu, Jay-Jiguang
Fu, Tong-Ming
Wu, Jiaqian
Xu, Hua
Zhang, Ningyan
An, Zhiqiang
Zheng, W. Jim
Presence of complete murine viral genome sequences in patient-derived xenografts
title Presence of complete murine viral genome sequences in patient-derived xenografts
title_full Presence of complete murine viral genome sequences in patient-derived xenografts
title_fullStr Presence of complete murine viral genome sequences in patient-derived xenografts
title_full_unstemmed Presence of complete murine viral genome sequences in patient-derived xenografts
title_short Presence of complete murine viral genome sequences in patient-derived xenografts
title_sort presence of complete murine viral genome sequences in patient-derived xenografts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017013/
https://www.ncbi.nlm.nih.gov/pubmed/33795676
http://dx.doi.org/10.1038/s41467-021-22200-5
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