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α干扰素对感染的T细胞和单核细胞中HIV复制的限制作用

Restriction of HIV replication in infected T cells and monocytes by interferon-alpha.

作者信息

Gendelman H E, Baca L, Turpin J A, Kalter D C, Hansen B D, Orenstein J M, Friedman R M, Meltzer M S

机构信息

Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD 20852.

出版信息

AIDS Res Hum Retroviruses. 1990 Aug;6(8):1045-9. doi: 10.1089/aid.1990.6.1045.

DOI:10.1089/aid.1990.6.1045
PMID:2121192
Abstract

Human recombinant interferon-alpha (IFN alpha) restricted viral replication in human immunodeficiency virus- (HIV) infected T cells and monocytes. With T cells, reverse transcriptase (RT) activity in culture fluids was reduced threefold from that of control infected cells by IFN treatment, but HIV p24 antigen levels were unchanged. In contrast, levels of p24 antigen and RT activity in lysates of IFN-treated infected cells were threefold greater than those of controls. These differences suggest that the mechanism for IFN-induced antiviral effects in HIV-infected T cells resides in the terminal events (assembly and release) of the virus replication cycle. Monocytes treated with IFN at the time of virus challenge showed no p24 antigen or RT activity, no HIV-specific mRNA, and no proviral DNA in cells for up to 3 weeks after infection. IFN treatment of chronically infected monocytes also decreased virus replication, as assessed by p24 antigen, mRNA and RT detection assays. However, levels of proviral DNA in the IFN-treated and control HIV-infected cells were indistinguishable. The presence of large quantities of proviral DNA in cells with little or no evidence for active transcription documents a situation approaching true microbiological latency.

摘要

人重组α干扰素(IFNα)可抑制人类免疫缺陷病毒(HIV)感染的T细胞和单核细胞中的病毒复制。对于T细胞,经干扰素处理后,培养液中的逆转录酶(RT)活性比未处理的对照感染细胞降低了三倍,但HIV p24抗原水平未变。相反,经干扰素处理的感染细胞裂解物中的p24抗原水平和RT活性比对照高三倍。这些差异表明,干扰素在HIV感染的T细胞中诱导抗病毒作用的机制存在于病毒复制周期的终末事件(组装和释放)中。在病毒攻击时用干扰素处理的单核细胞,在感染后长达3周的时间里,细胞内未检测到p24抗原或RT活性、HIV特异性mRNA以及前病毒DNA。通过p24抗原、mRNA和RT检测试验评估,用干扰素处理慢性感染的单核细胞也可减少病毒复制。然而,经干扰素处理的HIV感染细胞和对照细胞中的前病毒DNA水平没有差异。在几乎没有或没有活性转录证据的细胞中存在大量前病毒DNA,这表明存在接近真正微生物潜伏状态的情况。

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