Global Analysis of Mouse Polyomavirus Infection Reveals Dynamic Regulation of Viral and Host Gene Expression and Promiscuous Viral RNA Editing

PLoS Pathogens

Gordon G. Carmichael¹  Michael O. Duff¹  Seth B. Garren¹  Yuvabharath Kondaveeti¹ 

[1] Department of Genetics and Genome Sciences, UCONN Health, Farmington, Connecticut, United States of America

关键词: Sequence alignment;    Mammalian genomics;    DNA replication;    Genomic libraries;    RNA alignment;    Polyadenylation;    Gene expression;    Virus effects on host gene expression;   

DOI  :  10.1371/journal.ppat.1005166

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Mouse polyomavirus (MPyV) lytically infects mouse cells, transforms rat cells in culture, and is highly oncogenic in rodents. We have used deep sequencing to follow MPyV infection of mouse NIH3T6 cells at various times after infection and analyzed both the viral and cellular transcriptomes. Alignment of sequencing reads to the viral genome illustrated the transcriptional profile of the early-to-late switch with both early-strand and late-strand RNAs being transcribed at all time points. A number of novel insights into viral gene expression emerged from these studies, including the demonstration of widespread RNA editing of viral transcripts at late times in infection. By late times in infection, 359 host genes were seen to be significantly upregulated and 857 were downregulated. Gene ontology analysis indicated transcripts involved in translation, metabolism, RNA processing, DNA methylation, and protein turnover were upregulated while transcripts involved in extracellular adhesion, cytoskeleton, zinc finger binding, SH3 domain, and GTPase activation were downregulated. The levels of a number of long noncoding RNAs were also altered. The long noncoding RNA MALAT1, which is involved in splicing speckles and used as a marker in many late-stage cancers, was noticeably downregulated, while several other abundant noncoding RNAs were strongly upregulated. We discuss these results in light of what is currently known about the MPyV life cycle and its effects on host cell growth and metabolism.

【 授权许可】

CC BY