Select language: Hrvatski English

Work package 1

Functional analysis of mouse cytomegalovirus genes

virusi razni-02Although the function of many of the MCMV genes has been elucidated, there still exist a large number of undetected and uncharacterized viral genes. Recent work applying ribosomal footprinting technology to the proteome of the human cytomegalovirus identified over 750 different viral proteins encoded in the 230 kb long HCMV genome (Stern-Ginossar et al., Science, 2012). This number is in stark contrast to previously predicted number of approsimately 200 protein coding genes. In addition to the vast coding potential, HCMV contains a substantial amount of non-coding RNAs (Gatherer et al., PNAS, 2011).These findings underscore the gaps in our current understanding of viral gene products and this in turn represents a major obstacle in the development of efficient antiviral drugs and/or vaccines.

In an effort to alleviate these problems and initiate a systematic characterization of MCMV gene functions we have performed a comprehensive analysis of the MCMV transcriptome in BALB/c MEF cells during lytic infection using cDNA cloning and sequencing of viral transcripts, as well as next-generation sequencing of polyadenylated viral RNA (Juranic Lisnić et al., PLOS Pathogens 2013). In this work we have detected numerous novel spliced and unspliced transcripts of MCMV. A striking fact, which emerged from this study is that the most highly expressed viral genes have no assigned functions.

The goal of this work package is a systematic determination of the function of the new MCMV transcripts, starting with the most highly expressed ones. Two outstanding examples of such transcripts detected in our study are the ones transcribed from the the m169-m168 and M116 regions of the MCMV genome.