title: Global reprogramming of the cellular translational landscape facilitates cytomegalovirus replication.
abstract: Unlike many viruses that suppress cellular protein synthesis, host mRNA translation and polyribosome formation are stimulated by human cytomegalovirus (HCMV). How HCMV impacts the translationally regulated cellular mRNA repertoire and its contribution to virus biology remains unknown. Using polysome profiling, we show that HCMV presides over the cellular translational landscape, selectively accessing the host genome to extend its own coding capacity and regulate virus replication. Expression of the HCMV UL38 mTORC1-activator partially recapitulates these translational alterations in uninfected cells. The signature of cellular mRNAs translationally stimulated by HCMV resembles pathophysiological states (such as cancer) where translation initiation factor levels or activity increase. In contrast, cellular mRNAs repressed by HCMV include those involved in differentiation and the immune response. Surprisingly, interfering with the virus-induced activation of cellular mRNA translation can either limit or enhance HCMV growth. The unanticipated extent to which HCMV specifically manipulates host mRNA translation may aid in understanding its association with complex inflammatory disorders and cancer.
authors.affiliation: Department of Microbiology and NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Caleb
authors.initials: C
authors.lastname: McKinney
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; NYU Center for Health Informatics and Bioinformatics, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Jiri
authors.initials: J
authors.lastname: Zavadil
authors.affiliation: Department of Microbiology and NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bianco
authors.affiliation: Department of Microbiology and NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Lora
authors.initials: L
authors.lastname: Shiflett
authors.affiliation: NYU Center for Health Informatics and Bioinformatics, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Brown
authors.affiliation: Department of Microbiology and NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA. Electronic address: ian.mohr@med.nyu.edu.
authors.forename: Ian
authors.initials: I
authors.lastname: Mohr
mesh_terms: D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003587:Cytomegalovirus / Q000472:pathogenicity / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D006801:Humans; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D036022:Capsid Proteins; D012333:RNA, Messenger; C539756:UL38 protein, human herpesvirus-5