Thriving under Stress: Selective Translation of HIV-1 Structural Protein mRNA during Vpr-Mediated Impairment of eIF4E Translation Activity

• DOI: 10.1371/journal.ppat.1002612
• Publication Date: 2012-03-23T13:05:31Z
• Authors: Amit Sharma; Alper Yilmaz; Kim Marsh; Alan Cochrane; Kathleen Boris-La...
• Keywords: EIF4E; Initiation factor; Stress granule; Translational regulation; Viral protein; EIF4EBP1

Translation is a regulated process and pivotal to proper cell growth homeostasis. All retroviruses rely on the host translational machinery for viral protein synthesis thus may be susceptible its perturbation in response stress, co-infection, and/or cycle arrest. HIV-1 infection arrests G2/M phase, potentially disrupting regulation of translation. In this study, we present evidence that downregulates translation lymphocytes, attributable arrest induced by accessory Vpr. The molecular basis suppression reduced accumulation active form initiation factor 4E (eIF4E). However, structural proteins sustained despite general production. mRNA due distinct composition ribonucleoprotein complexes. RNA-coimmunoprecipitation assays determined unspliced singly spliced transcripts are predominantly associated with nuclear cap binding 80 (CBP80) contrast completely-spliced cellular mRNAs eIF4E. complex (CBC)-bound demonstrated ribosomal RNA profile analyses. Thus, our findings have uncovered maintenance CBC association novel mechanism used bypass downregulation eIF4E activity sustain synthesis. We speculate subset CBP80-bound contribute recovery from significant including human retrovirus infection.