TY - JOUR
T1 - Murine Polyomavirus encodes a microRNA that cleaves early RNA transcripts but is not essential for experimental infection
AU - Sullivan, Christopher S.
AU - Sung, Chang K.
AU - Pack, Christopher D.
AU - Grundhoff, Adam
AU - Lukacher, Aron E.
AU - Benjamin, Thomas L.
AU - Ganem, Don
N1 - Funding Information:
We thank Steve Dilworth and Bob Garcea for kindly providing antibodies used in these studies. The initial impetus for this work was greatly aided by helpful suggestions from and the PhD thesis work of Richard Treisman (London Research Institute). In addition, the authors acknowledge helpful conversations regarding this work with Brian Schaffhausen, Janet Butel, and Jim Pipas. CSS is supported by start-up funds from the University of Texas at Austin and a fellowship from the Institute for Cellular and Molecular Biology at the University of Texas at Austin. Portions of this work were supported by grants from the National Cancer Institute RO1 CA 90992 to TB, RO1 CA 71971 to AL, and grant F32AC72939 to CP.
PY - 2009/4/25
Y1 - 2009/4/25
N2 - MicroRNAs are small regulatory RNAs that post-transcriptionally regulate gene expression and can be encoded by viral as well as cellular genomes. The functions of most viral miRNAs are unknown and few have been studied in an in vivo context. Here we show that the murine polyomavirus (PyV) encodes a precursor microRNA that is processed into two mature microRNAs, both of which are active at directing the cleavage of the early PyV mRNAs. Furthermore, we identify a deletion mutant of polyomavirus that is defective in encoding the microRNAs. This mutant replicates normally and transforms cultured cells with efficiencies comparable to wildtype PyV. The miRNA mutant is competent to establish a transient infection of mice following parenteral inoculation, and is cleared post infection at approximately the same rate as the wildtype virus. In addition, under these laboratory conditions, we observe no differences in anti-viral CD8 T cell responses. These results indicate that PyV miRNA expression is not essential for infection of cultured cells or experimentally inoculated mice, and raise the possibility that its role in natural infection might involve aspects of acquisition or spread that are not recapitulated by experimental inoculation.
AB - MicroRNAs are small regulatory RNAs that post-transcriptionally regulate gene expression and can be encoded by viral as well as cellular genomes. The functions of most viral miRNAs are unknown and few have been studied in an in vivo context. Here we show that the murine polyomavirus (PyV) encodes a precursor microRNA that is processed into two mature microRNAs, both of which are active at directing the cleavage of the early PyV mRNAs. Furthermore, we identify a deletion mutant of polyomavirus that is defective in encoding the microRNAs. This mutant replicates normally and transforms cultured cells with efficiencies comparable to wildtype PyV. The miRNA mutant is competent to establish a transient infection of mice following parenteral inoculation, and is cleared post infection at approximately the same rate as the wildtype virus. In addition, under these laboratory conditions, we observe no differences in anti-viral CD8 T cell responses. These results indicate that PyV miRNA expression is not essential for infection of cultured cells or experimentally inoculated mice, and raise the possibility that its role in natural infection might involve aspects of acquisition or spread that are not recapitulated by experimental inoculation.
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U2 - 10.1016/j.virol.2009.02.017
DO - 10.1016/j.virol.2009.02.017
M3 - Article
C2 - 19272626
AN - SCOPUS:63549120842
SN - 0042-6822
VL - 387
SP - 157
EP - 167
JO - Virology
JF - Virology
IS - 1
ER -