Induction of CD4 expression and human immunodeficiency virus type 1 replication by mutants of the interferon-inducible protein kinase PKR

J Virol. 1997 Feb;71(2):1718-25. doi: 10.1128/JVI.71.2.1718-1725.1997.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD4 Antigens / genetics*
  • Gene Expression Regulation, Viral*
  • Gene Transfer Techniques
  • HIV Infections / virology*
  • HIV-1 / physiology*
  • Humans
  • Interferons / pharmacology
  • Jurkat Cells
  • Protein Serine-Threonine Kinases / agonists
  • Protein Serine-Threonine Kinases / genetics*
  • Virus Replication*
  • eIF-2 Kinase

Substances

  • CD4 Antigens
  • Interferons
  • Protein Serine-Threonine Kinases
  • eIF-2 Kinase