An mRNA cap-binding complex in giant viruses controls protein synthesis

In contrast to living organisms, viruses lack the machinery necessary for protein synthesis, instead co-opting host factors to translate viral transcripts. Giant DNA viruses, which encode putative orthologs of translation factors, challenge this dogma and blur the line between cellular and acellular biology. Here, we discover a complete mRNA cap-binding complex in mimivirus that we name viral IF4F. This complex associates with host ribosomes to orchestrate the temporally regulated synthesis of structural proteins critical for assembly of viral progeny. The m7G cap-binding subunit of viral IF4F has evolved specificity for viral cap structures through additional interactions with methylated adenosines in mRNAs. Viral IF4F further facilitates dynamic gene expression required to evade host abiotic stresses that normally restrict viral replication. Our study thereby extends a paradigm of eukaryotic translation regulation to include viruses and illuminates a series of evolutionary innovations to a core process of life. Overall design: Ribosome profiling (RNA-seq and RIBO-seq) of Acanthamoeba castellanii infected with APMV WT and mutant viruses lacking viral translation factors (APMV ?4A, ?4E, ?4G). Samples were collected at early (4 h) and late (8 h) times of infection.