Granulocyte-macrophage colony-stimulating factor inhibits HIV-1 replication in monocyte-derived macrophages.
BACKGROUND
Previous studies of the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on HIV-1 replication in macrophages have had inconsistent results, variously reporting no effect, augmentation or inhibition of viral replication.


OBJECTIVE
To investigate the regulation of HIV-1 in monocyte-derived macrophages (MDM) by GM-CSF in vitro.


METHODS
The role of GM-CSF on HIV-1 replication was assessed as supernatant and intracellular p24 antigen concentrations and by HIV-1 DNA and mRNA production under different culture conditions. Expression of CD4 and CCR5 receptors was examined. The effect of GM-CSF with an E21R mutation, which binds only to the alpha-chain of GM-CSF receptor, was used as an additional control.


RESULTS
GM-CSF consistently suppressed HIV-1 replication in human MDM in vitro, as assessed by supernatant and intracellular p24 antigen concentrations and HIV-1 gag mRNA expression. The inhibitory effect of GM-CSF on HIV-1 replication was observed regardless of HIV-1 strain, source of GM-CSF, stage of MDM maturation or timing of GM-CSF exposure in relation to HIV-1 infection. The effect was dose dependent and reversed by addition of a neutralizing monoclonal antibody (4D4). Flow cytometric analysis of surface expression of CD4 and CCR5 indicates that GM-CSF does not affect HIV-1 entry into MDM. Analysis of intracellular HIV-1 DNA and mRNA suggests that HIV-1 replication is inhibited at or before transcription. E21R GM-CSF had no effect on HIV-1 replication in MDM.


CONCLUSIONS
GM-CSF regulates HIV-1 replication in MDM, inhibiting HIV-1 replication through binding to the beta-chain of the GM-CSF receptor.
Kedzierska
K
K
AIDS Pathogenesis Research Unit, Macfarlane Burnet Centre for Medical Research, Melbourne, Australia.
Maerz
A
A
Warby
T
T
Jaworowski
A
A
Chan
H
H
Mak
J
J
Sonza
S
S
Lopez
A
A
Crowe
S
S
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015750:Genes, gag; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000821:virology*; D009000:Monocytes / Q000187:drug effects / Q000821:virology*; D012333:RNA, Messenger; D014779:Virus Replication / Q000187:drug effects*
D016655:HIV Core Protein p24; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor