Kazazi F, Mathijs J M, Chang J, Malafiej P, Lopez A, Dowton D, Sorrell T C, Vadas M A, Cunningham A L
Department of Virology, Westmead Hospital, Sydney, New South Wales, Australia.
J Gen Virol. 1992 Apr;73 ( Pt 4):941-9. doi: 10.1099/0022-1317-73-4-941.
Recombinant interleukin 4 (IL-4) stimulated extracellular (EC) and intracellular (IC) production of human immunodeficiency virus (HIV) from infected human blood-derived monocytes and macrophages when incubated with the cells after but not before virus inoculation. Significant stimulation was observed in 20 of 27 experiments with monocytes (inoculated with HIV immediately after adherence) and 10 of 13 experiments with macrophages (inoculated after 5 days adherence) using a total of 30 normal donors of monocytes and macrophages, and 11 recent isolates of monocytotropic HIV strains (after one passage in mononuclear cells). Marked increases in EC and IC HIV antigen were observed in some experiments, which were comparable with the maximal stimulatory effects of other cytokines such as IL-2. IL-4 also had similar effects on infectious HIV concentration as measured by reverse transcriptase and TCID50 assays. Antibody to IL-4 prevented the stimulatory effect of the cytokine. The proportion of monocytes and macrophages infected by HIV, as determined by in situ hybridization, also increased after incubation with IL-4 for 7 days. The most marked effects were observed with HIV-infected macrophages, for which the proportion of unstimulated infected cells was lower (35 to 45% increasing to 66 to 70% with IL-4 treatment). There was also an increased proportion of cells with high granule concentrations, suggesting that IL-4 increases the intracellular concentration of viral nucleic acids. This was supported by semi-quantitative hybridization experiments showing that total HIV RNA increased in IL-4-stimulated monocytes 48 to 96 h after HIV inoculation. A marked increase in aggregates was observed on day 7 in HIV-infected monocytes treated with IL-4, compared to that in HIV-infected cells alone or IL-4-treated uninfected monocytes. These findings suggest that IL-4 stimulates HIV replication in the early phases of infection and may also facilitate virus transmission by aggregate formation.
重组白细胞介素4（IL-4）在病毒接种后而非接种前与受感染的人血单核细胞和巨噬细胞一起孵育时，可刺激细胞外（EC）和细胞内（IC）产生人类免疫缺陷病毒（HIV）。在总共30名单核细胞和巨噬细胞的正常供体以及11株嗜单核细胞HIV毒株（在单核细胞中传代一次后）的27个单核细胞实验（贴壁后立即接种HIV）中的20个以及13个巨噬细胞实验（贴壁5天后接种）中的10个中观察到了显著的刺激作用。在一些实验中观察到EC和IC HIV抗原显著增加，这与其他细胞因子如IL-2的最大刺激作用相当。通过逆转录酶和TCID50测定，IL-4对感染性HIV浓度也有类似影响。抗IL-4抗体可阻止该细胞因子的刺激作用。通过原位杂交确定，与IL-4孵育7天后，被HIV感染的单核细胞和巨噬细胞比例也增加。在HIV感染的巨噬细胞中观察到最显著的效果，未刺激的感染细胞比例较低（35%至45%，经IL-4处理后增至66%至70%）。颗粒浓度高的细胞比例也增加，表明IL-4增加了病毒核酸的细胞内浓度。这得到了半定量杂交实验的支持，该实验表明HIV接种后48至96小时，IL-4刺激的单核细胞中总HIV RNA增加。与单独感染HIV的细胞或经IL-4处理的未感染单核细胞相比，用IL-4处理的HIV感染单核细胞在第7天观察到聚集体显著增加。这些发现表明，IL-4在感染早期刺激HIV复制，并且还可能通过聚集体形成促进病毒传播。
