Active cellular infection of myeloid cells is required for HIV-1-mediated suppression of interleukin-12 p40 expression.
Immunodeficiency during HIV infection is associated with impaired production of interleukin-12 (IL-12). Here we examine the requirement for active cellular infection, the role of other cytokines, and the molecular target of HIV-mediated suppression of IL-12. The reduction in LPS-induced IL-12 p40 protein and mRNA following acute in vitro HIV infection of THP-1 cells and monocytes was not attributed to IL-10 or TGF-beta activity and was not restored by priming with IL-4, IL-13, or IFN-gamma. Suppression of IL-12 was dependent upon active cellular infection and replication and not due to any soluble host or viral factors in HIV-infected cultures. Significant reduction in transcription of IL-12 p40 was observed following acute HIV infection. These results suggest that impaired IL-12 production in HIV-infected myeloid cells occurs, in part, via disruption of IL-12 p40 gene expression in a manner that requires cellular infection, highlighting the need to study myeloid cells in isolation during acute HIV-1 infection.
Ottawa Health Research Institute, Ottawa, Ont., Canada.
Kelley A
KA
Chambers
Karl G
KG
Parato
Jonathan B
JB
Angel
D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D016655:HIV Core Protein p24 / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D021122:Protein Subunits; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D053762:Interleukin-12 Subunit p40; D018793:Interleukin-13; D008070:Lipopolysaccharides; D021122:Protein Subunits; D011500:Protein Synthesis Inhibitors; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D003513:Cycloheximide