Inhibition of Human Immunodeficiency Virus Replication in Differentiating Monocytes by Interleukin 10 Occurs in Parallel with Inhibition of Cellular RNA Expression

Abstract

The mechanism of inhibition of HIVBa-L replication by interleukin 10 (IL-10) in primary monocytes and macrophages at various stages of maturation was investigated using semiquantitative PCR for reverse-transcribed HIV DNA, and Northern hybridization for HIV mRNA expression in comparison with extracellular p24 antigen. Pretreatment of monocytes with IL-10 markedly inhibited expression of both unspliced and spliced HIV RNA, reaching a nadir at 7 days and recovering to normal levels by 10 days after a single application. The optimum inhibitory concentration was 25 ng/ml. Less inhibition of HIV RNA expression was observed when IL-10 was added after HIV infection of monocytes and the inhibitory effect progressively declined to negligible levels as monocytes matured into macrophages over 10 days. IL-10 also downregulated the expression of cellular genes, including the transferrin receptor, 28S rRNA, and GAPDH. The kinetics of the inhibition of cellular mRNAs correlated with the inhibition of HIV RNA and also declined as monocytes matured into macrophages. In contrast, IL-10 did not inhibit cellular mRNA expression in the macrophage cell line THP-1. Neutralizing polyclonal antibody to IL-10 reversed all its inhibitory effects. Interaction of IL-10 and TNF-alpha in combination were generally antagonistic in their effects on HIV transcription. IL-10 prevented stimulation of HIV RNA expression by TNF-alpha after preincubation with monocytes for 48 hr. IL-10 had no effect on the levels of HIV cDNA or the process of initiation and completion of reverse transcription. The inhibitory effect of IL-10 on HIV replication in maturing monocytes was probably mediated mainly by inhibition of cellular gene expression and inhibition of maturation of monocytes into macrophages and their activation, with consequent downregulation of HIV mRNA.

Macrophages and HIV-1: dangerous liaisons

“…IL-10 and TNF- have been shown to have different effects on HIV replication in macrophages depending on the experimental conditions. Indeed, treatment of primary macrophages with IL-10 abrogates HIV-1 infection by inhibiting the production of both spliced and unspliced HIV-1 RNA transcripts and by interfering with protein processing Naif et al, 1996). However, another study found that IL-10 promotes the productive infection of monocytes by the R5 virus by selectively upregulating CCR5 and increasing viral entry (Sozzani et al, 1998).…”

Potential New Anti-Human Immunodeficiency Virus Type 1 Compounds Depress Virus Replication in Cultured Human Macrophages

“…MDMs were cultured from the peripheral blood of healthy HIV-seronegative donors and infected with the laboratory-adapted M-tropic strain HIV-1 BaL (multiplicity of infection [MOI], 0.02) as described previously (10). In the first set of experiments, cells from four donors were exposed to the test compounds at 0, 1, and 10 M over 28 days.…”

Prostaglandin E2Increases Bovine Leukemia VirustaxandpolmRNA Levels via Cyclooxygenase 2: Regulation by Interleukin-2, Interleukin-10, and Bovine Leukemia Virus

“…COX-2 and PGE 2 also inhibit programmed cell death and facilitate tumor formation (33,34), and thus these activities might promote lymphosarcoma and leukemia with other carcinogenic factors, such as Bcl-2 and BLV Tax protein, in BLV infection. Thus, in other retrovirus infections, the inhibitory function of IL-10 on human immunodeficiency virus expression has been reported (24,30,31). Most studies have utilized macrophage cell lines and primary macrophages, while the studies with T-cell lines or primary T cells failed to demonstrate the IL-10 inhibition of human immunodeficiency virus expression.…”