Novel function of prothymosin alpha as a potent inhibitor of human immunodeficiency virus type 1 gene expression in primary macrophages
Novel function of prothymosin alpha as a potent inhibitor of human immunodeficiency virus type 1 gene expression in primary macrophages
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DOI：
10.1128/jvi.00589-06
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发表时间：
2006-09-01
影响因子：
5.4
通讯作者：
Klotman, Mary
中科院分区：
文献类型：
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作者：
Mosoian, Arevik;Teixeira, Avelino;Klotman, Mary
CD8(+) T淋巴细胞通过细胞毒性主要组织相容性复合物-限制性途径以及通过分泌非细胞毒性可溶性抑制因子控制人类免疫缺陷病毒1型（HIV-1）感染。CD8（+）细胞上清液的几种成分已被确定有助于后者的活性。在这项研究中，我们报道了在猴疱疹病毒转化的CD8(+) t细胞系k# 1 50K细胞培养基中发现的一种蛋白原胸腺酶α (ProT α)具有有效的hiv -1抑制活性。从CD8（+）细胞上清液的hiv -1抑制部分中去除天然ProT α可去除抑制活性，支持其通过可溶性介质抑制的作用。ProT α是一种丰富的酸性肽，据报道存在于细胞核中，与细胞增殖和转录激活有关。在本报告中，我们证明了ProT α抑制HIV-1复制，其活性是靶细胞特异性的，并且抑制发生在病毒整合之后。天然和重组ProT α蛋白能有效抑制巨噬细胞中HIV-1长末端重复（LTR）驱动基因的表达。此外，在慢病毒载体（巨细胞病毒和磷酸甘油酸激酶）中使用不同启动子的研究表明，ProTa对病毒复制的抑制不是HIV LTR特异性的。
CD8(+) T lymphocytes control human immunodeficiency virus type 1 (HIV-1) infection by a cytotoxic major histocompatibility complex-restricted pathway as well as by secretion of noncytotoxic soluble inhibitory factors. Several components of CD8(+) cell supernatants have been identified that contribute to the latter activity. In this study we report that prothymosin alpha (ProT alpha), a protein found in the cell culture medium of the herpesvirus saimiri-transformed CD8(+) T-cell line, K#1 50K, has potent HIV-1-inhibitory activity. Depletion of native ProT alpha from an HIV-1-inhibitory fraction of CD8(+) cell supernatants removes the inhibitory activity, supporting its role in inhibition via soluble mediators. ProT alpha is an abundant, acidic peptide that has been reported to be localized in the nucleus and associated with cell proliferation and activation of transcription. In this report we demonstrate that ProT alpha suppresses HIV-1 replication, its activity is target cell specific, and inhibition occurs following viral integration. Native and recombinant ProT alpha protein potently inhibit HIV-1 long terminal repeat (LTR)-driven gene expression in macrophages. Furthermore studies using different promoters in lentiviral vectors (cytomegalovirus and phosphoglycerate kinase) revealed that suppression of viral replication by ProTa is not HIV LTR specific.