Abstract
mRNA translation requires the ordered assembly of translation initiation factors and ribosomal subunits on a transcript. Host signaling pathways regulate each step in this process to match levels of protein synthesis to environmental cues. In response to infection, cells activate multiple defenses that limit viral protein synthesis, which viruses must counteract to successfully replicate. Human cytomegalovirus (HCMV) inhibits host defenses that limit viral protein expression and manipulates host signaling pathways to promote the expression of both host and viral proteins necessary for virus replication. Here we review key regulatory steps in mRNA translation, and the strategies used by HCMV to maintain protein synthesis in infected cells.
Highlights
Viruses are completely reliant on the host translation machinery for the synthesis of viral proteins, since no virus encodes a ribosome
The target of rapamycin (TOR) kinase is conserved throughout eukaryotes, where it plays a critical role in modulating protein synthesis in response to the intracellular and extracellular environment ([54,55] reviewed in [1])
Overall levels of protein synthesis are maintained in Human cytomegalovirus (HCMV)-infected cells [91]. As both host and viral mRNAs rely on the same pool of ribosomes for their translation, HCMV mRNAs must efficiently compete with host transcripts for access to the translation machinery to ensure synthesis of viral proteins
Summary
Viruses are completely reliant on the host translation machinery for the synthesis of viral proteins, since no virus encodes a ribosome. Viral and host mRNAs must compete for access to ribosomes. Viruses must counteract host defenses that inactivate the translation machinery after sensing viral infection. Human cytomegalovirus (HCMV) effectively antagonizes host defenses that limit viral protein expression. HCMV manipulates multiple host signaling pathways to ensure the continued synthesis of both host and viral proteins needed for virus replication. The interface between viral mRNAs and the host translation machinery serves as a critical determinant for successful HCMV infection. The purpose of this review is to summarize key steps in the regulation of mRNA translation, and strategies by which HCMV manipulates the host translation machinery to benefit virus replication
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