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

Zihao Yuan, Xuejun Fan, Jay-Jiguang Zhu, Tong-Ming Fu, Jiaqian Wu, Hua Xu, Ningyan Zhang, Zhiqiang An () and W. Jim Zheng ()
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Zihao Yuan: University of Texas Health Science Center at Houston
Xuejun Fan: McGovern Medical SchoolUniversity of Texas Health Science Center at Houston
Jay-Jiguang Zhu: University of Texas Health Science Center at Houston
Tong-Ming Fu: McGovern Medical SchoolUniversity of Texas Health Science Center at Houston
Jiaqian Wu: University of Texas Health Science Center at Houston
Hua Xu: University of Texas Health Science Center at Houston
Ningyan Zhang: McGovern Medical SchoolUniversity of Texas Health Science Center at Houston
Zhiqiang An: McGovern Medical SchoolUniversity of Texas Health Science Center at Houston
W. Jim Zheng: University of Texas Health Science Center at Houston

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-22200-5

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