HCMV, as any other virus, is completely dependent on the translation machinery of the host cell to synthesize the viral proteins necessary for its productive growth. However, our understanding of how DNA viruses co-opt the translation machinery remains largely elusive.
We use RNA-seq and ribosome profiling (deep sequencing of ribosome protected fragments) to globally map changes in host genes transcription and translation along HCMV infections.
These comprehensive and simultaneous measurements revealed that most of the changes in host genes translation were the consequence of change in their mRNA levels implying that the regulation of most human genes along infection occur at the transcriptional level. Nevertheless, a significant subset of host genes showed drastic changes in their translation efficiency along infection and these genes cluster into few defined clusters with defined kinetics that suggest common regulators. Integration of our translation measurements with recent measurements of steady state protein levels enabled the identification of novel host proteins that are actively targeted for degradation during HCMV infection. Our results demonstrate how measurements of transcriptional and translation landscape during infection can reveal novel aspects host-pathogen interactions even in a well studied pathogen such as HCMV.
