The role of interferons in the control of HIV replication in macrophages.
Interferons can suppress the replication of certain retroviruses, including oncogenic murine retroviruses. In recent studies of the Lentivirinae subfamily of Retroviridae, an endogenous, immunologically induced interferon was found to restrict the replication of visna in macrophages. Several studies have shown that the replication of a human lentivirus, the human immunodeficiency virus (HIV), is also susceptible to interferon control. Here we review the evidence that interferons can protect macrophages from HIV in vitro. Macrophages treated with interferons or bacterial lipopolysaccharide (LPS) become essentially nonpermissive for HIV replication. Using the polymerase chain reaction to amplify HIV proviral DNA, we now report that interferon and LPS act to restrict the formation of proviral DNA. Effects on any several steps in the HIV life cycle may explain this data, and single-cycle infection studies are needed to define the precise roles of these agents. Taken together, these findings may explain the restricted replication of HIV in macrophages in vivo and suggest an antiviral role for endogenously produced interferon in the maintenance of the prolonged asymptomatic period which typically follows HIV infection. Interferons are currently undergoing clinical trials to determine if they have antiviral effects in HIV-infected patients.
Kornbluth
R S
RS
Department of Medicine, University of California, San Diego.
Oh
P S
PS
Munis
J R
JR
Cleveland
P H
PH
Richman
D D
DD
D002478:Cells, Cultured; D004279:DNA, Viral / Q000378:metabolism; D006678:HIV / Q000254:growth & development*; D015658:HIV Infections / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D016133:Polymerase Chain Reaction; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D004279:DNA, Viral; D007370:Interferon Type I; D008070:Lipopolysaccharides; D007371:Interferon-gamma; D007372:Interferons