Induction of CD4 expression and human immunodeficiency virus type 1 replication by mutants of the interferon-inducible protein kinase PKR.
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.
Nagai
K
K
Department of Oncology, McGill University, Montreal, Canada.
Wong
A H
AH
Li
S
S
Tam
W N
WN
Cuddihy
A R
AR
Sonenberg
N
N
Mathews
M B
MB
Hiscott
J
J
Wainberg
M A
MA
Koromilas
A E
AE
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
D015704:CD4 Antigens; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase