title: Induction of CD4 expression and human immunodeficiency virus type 1 replication by mutants of the interferon-inducible protein kinase PKR.
abstract: Replication of the human immunodeficiency virus type 1 (HIV-1) is inhibited by interferons (IFNs), and the IFN-inducible protein kinase PKR is thought to mediate this effect by regulating protein synthesis. Here we report that ectopic expression of dominant negative PKR mutants in Jurkat cells induces HIV-1 replication. Specifically, expression of CD4 is upregulated by the PKR mutants, and this correlates with an induction of HIV-1 binding and proviral DNA synthesis upon HIV-1 infection. Moreover, activation of NF-kappaB was induced by an RNA binding-defective mutant of PKR. Thus, it appears that PKR, in addition to translational control, is involved in HIV-1 replication by modulating virus binding through the regulation of CD4 expression and virus gene expression through the activation of NF-kappaB.
authors.affiliation: Department of Oncology, McGill University, Montreal, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Nagai
authors.forename: A H
authors.initials: AH
authors.lastname: Wong
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: W N
authors.initials: WN
authors.lastname: Tam
authors.forename: A R
authors.initials: AR
authors.lastname: Cuddihy
authors.forename: N
authors.initials: N
authors.lastname: Sonenberg
authors.forename: M B
authors.initials: MB
authors.lastname: Mathews
authors.forename: J
authors.initials: J
authors.lastname: Hiscott
authors.forename: M A
authors.initials: MA
authors.lastname: Wainberg
authors.forename: A E
authors.initials: AE
authors.lastname: Koromilas
mesh_terms: D015704:CD4 Antigens / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D018014:Gene Transfer Techniques; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D019169:Jurkat Cells; D017346:Protein Serine-Threonine Kinases / Q000819:agonists / Q000235:genetics*; D014779:Virus Replication; D019892:eIF-2 Kinase
chemical_list: D015704:CD4 Antigens; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase