title: HIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA Cap-Binding Complex.
abstract: Stress granules (SGs) are dynamic accumulations of stalled preinitiation complexes and translational machinery that assemble under stressful conditions. Sodium selenite (Se) induces the assembly of noncanonical type II SGs that differ in morphology, composition, and mechanism of assembly from canonical SGs. Se inhibits translation initiation by altering the cap-binding activity of eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1). In this work, we show that human immunodeficiency virus type 1 (HIV-1) Gag is able to block the assembly of type II noncanonical SGs to facilitate continued Gag protein synthesis. We demonstrate that expression of Gag reduces the amount of hypophosphorylated 4EBP1 associated with the 5' cap potentially through an interaction with its target, eIF4E. These results suggest that the assembly of SGs is an important host antiviral defense that HIV-1 has evolved for inhibition through several distinct mechanisms.
  
  
  OBJECTIVE
  The antiviral stress response is an important host defense that many viruses, including HIV-1, have evolved to evade. Selenite induces a block in translation and leads to stress granule assembly through the sequestration of eIF4E by binding hypophosphorylated 4EBP1. In this work, we demonstrate that in the face of selenite-induced stress, HIV-1 is able to maintain Gag mRNA translation and to elicit a blockade to selenite-induced stress granule assembly by altering the amount of hypophosphorylated 4EBP1 on the 5' cap.
authors.affiliation: HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada Department of Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cinti
authors.affiliation: HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Le Sage
authors.affiliation: HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada.
authors.forename: Marwan
authors.initials: M
authors.lastname: Ghanem
authors.affiliation: HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada Department of Medicine, McGill University, Montréal, Québec, Canada Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada andrew.mouland@mcgill.ca.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mouland
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism; D039381:RNA Cap-Binding Proteins / Q000378:metabolism*; D020887:Selenious Acid / Q000378:metabolism*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; D039381:RNA Cap-Binding Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D020887:Selenious Acid