Abstract
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.
Highlights
Mouse polyomavirus (MPyV) is a small circular double-stranded DNA virus with a life cycle that is divided into distinct early and late phases of infection
This study serves to provide a global view of the MPyV infection by utilizing Illumina sequencing to observe changes in total RNA from both the virus and the host cell as well as applying new methods to more
MPyV Large T antigen is involved in a variety of roles during the course of infection, including altering host protein pathways to promote virus production [13], blocking the interferon antiviral response [14], recruiting host DNA replication factors to the viral origin [15,16,17], acting as a helicase for viral DNA replication [18], and modulating late gene transcription [19]
Summary
MPyV is a small circular double-stranded DNA virus with a life cycle that is divided into distinct early and late phases of infection. During the early phase the virus expresses both earlystrand and late-strand transcripts from its bidirectional noncoding control region (Fig 1A), but the early-strand transcripts preferentially accumulate and are spliced into mRNAs for Large, middle, and small tumor antigens [1,2,3,4,5,6,7,8,9]. These early gene products induce host cell S phase entry and the virus utilizes host factors for viral DNA replication [10]. Large T antigen exhibits both J domain dependent and independent binding to pRB [26]
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