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Inhibition of HIV type 1 replication by human T lymphotropic virus types 1 and 2 tax proteins in vitro

机译:1型和2型人类T淋巴病毒在体外抑制1型HIV复制

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Patients with HIV-1 and human T-lymphotropic virus type 2 (HTLV-2) coinfections often exhibit a clinical course similar to that seen in HIV-1-infected individuals who are long-term nonprogressors. These findings have been attributed in part to the ability of HTLV-2 to activate production of antiviral chemokines and to downregulate the CCR5 coreceptor on lymphocytes. To further investigate these observations, we tested the ability of recombinant Tax1 and Tax2 proteins to suppress HIV-1 viral replication in vitro. R5-tropic HIV-1 (NLAD8)-infected peripheral blood mononuclear cells (PBMCs) were treated daily with recombinant Tax1 and Tax2 proteins (dosage range 1-100 pM). Culture supernatants were collected at intervals from days 1 to 22 postinfection and assayed for levels of HIV-1 p24 antigen by ELISA. Treatment of PBMCs with Tax2 protein resulted in a significant reduction in HIV-1 p24 antigen levels (p<0.05) at days 10, 14, and 18 postinfection compared to HIV-1-infected or mock-treated PBMCs. This was preceded by the detection of increased levels of CC-chemokines MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5 on days 1-7 of infection. Similar, but less robust inhibition was observed in Tax1-treated PBMCs. These results support the contention that Tax1 and Tax2 play a role in generating antiviral responses against HIV-1 in vivo and in vitro.
机译:HIV-1和2型人类T淋巴病毒(HTLV-2)合并感染的患者通常表现出与长期感染非HIV-1感染者相似的临床病程。这些发现部分归因于HTLV-2激活抗病毒趋化因子产生并下调淋巴细胞上CCR5受体的能力。为了进一步研究这些发现,我们测试了重组Tax1和Tax2蛋白在体外抑制HIV-1病毒复制的能力。每天用重组Tax1和Tax2蛋白(剂量范围1-100 pM)处理感染R5的HIV-1(NLAD8)的外周血单核细胞(PBMC)。在感染后第1至22天的间隔中收集培养物上清液,并通过ELISA测定HIV-1 p24抗原的水平。与HIV-1感染或模拟治疗的PBMC相比,用Tax2蛋白处理PBMC导致在感染后第10、14和18天HIV-1 p24抗原水平显着降低(p <0.05)。在感染的第1至7天,检测到CC趋化因子MIP-1α/ CCL3,MIP-1β/ CCL4和RANTES / CCL5水平升高。在Tax1处理过的PBMC中观察到了类似的抑制作用,但抑制作用较弱。这些结果支持以下论点:Tax1和Tax2在体内和体外对HIV-1产生抗病毒反应中起作用。

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