title: Interference of interleukin-10 with human immunodeficiency virus type 1 replication in primary monocyte-derived macrophages.
abstract: Previously we demonstrated an inhibitory effect of interleukin-4 (IL-4) on establishment of human immunodeficiency virus type 1 (HIV-1) infection in primary macrophages. The reported similarities between the biological effects of IL-4 and IL-10 prompted us to study the effect of IL-10 on HIV-1 replication. Treatment of primary macrophages with IL-10 resulted in inhibition of HIV-1 infection. This inhibitory effect was specific for macrophages, since IL-10 did not interfere with HIV-1 replication in primary T cells. Semiquantitative PCR analysis excluded an inhibitory effect of IL-10 on virus entry and reverse transcription. Effects of IL-10 on HIV-1 long terminal repeat-driven chloramphenicol acetyltransferase activity also could not be demonstrated in a transient expression system in primary derived macrophages. In agreement with this, Northern (RNA) blot analysis demonstrated equal amounts of viral RNA species irrespective of IL-10 treatment, also excluding an inhibitory effect on elongation of virus transcription. Monocyte-derived macrophages (MDM) treated with IL-10 after HIV-1 inoculation showed accumulation of apparently mature p24 protein suggestive of an inhibitory effect at the level of virus assembly. IL-10 treatment of MDM prior to HIV-1 inoculation did not result in accumulation of p24 protein. Immunoblot analysis indeed showed the absence of mature p24 and gp120 but accumulation of the Pr53 gag-encoded protein in HIV-1-inoculated, IL-10-pretreated MDM, suggesting an inhibitory effect at the level of protein processing. A combination of IL-4 and IL-10 resulted in a cumulative inhibitory effect on HIV-1 replication in MDM. The recent observation that in the course of HIV-1 infection a shift occurs in the production of IL-2/gamma interferon toward enhanced IL-4 and IL-10 production and the reported shift from preferential macrophage-tropic towards preferential T-cell-tropic HIV-1 variants with progression of disease suggest that cytokines have an important role in the in vivo regulation of HIV-1 tropism.
authors.affiliation: Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: N A
authors.initials: NA
authors.lastname: Kootstra
authors.forename: A
authors.initials: A
authors.lastname: van 't Wout
authors.forename: H G
authors.initials: HG
authors.lastname: Huisman
authors.forename: F
authors.initials: F
authors.lastname: Miedema
authors.forename: H
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008264:Macrophages / Q000821:virology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000821:virology; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D016655:HIV Core Protein p24; D016753:Interleukin-10; D015847:Interleukin-4