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SAMHD1在单核细胞衍生巨噬细胞中对嗜巨噬细胞性1型人类免疫缺陷病毒的适度限制作用

Moderate restriction of macrophage-tropic human immunodeficiency virus type 1 by SAMHD1 in monocyte-derived macrophages.

作者信息

Taya Kahoru, Nakayama Emi E, Shioda Tatsuo

机构信息

Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.

出版信息

PLoS One. 2014 Mar 5;9(3):e90969. doi: 10.1371/journal.pone.0090969. eCollection 2014.

Abstract

Macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains are able to grow to high titers in human monocyte-derived macrophages. However, it was recently reported that cellular protein SAMHD1 restricts HIV-1 replication in human cells of the myeloid lineage, including monocyte-derived macrophages. Here we show that degradation of SAMHD1 in monocyte-derived macrophages was associated with moderately enhanced growth of the macrophage-tropic HIV-1 strain. SAMHD1 degradation was induced by treating target macrophages with vesicular stomatitis virus glycoprotein-pseudotyped human immunodeficiency virus type 2 (HIV-2) particles containing viral protein X. For undifferentiated monocytes, HIV-2 particle treatment allowed undifferentiated monocytes to be fully permissive for productive infection by the macrophage-tropic HIV-1 strain. In contrast, untreated monocytes were totally resistant to HIV-1 replication. These results indicated that SAMHD1 moderately restricts even a macrophage-tropic HIV-1 strain in monocyte-derived macrophages, whereas the protein potently restricts HIV-1 replication in undifferentiated monocytes.

摘要

嗜巨噬细胞的1型人类免疫缺陷病毒(HIV-1)毒株能够在人单核细胞衍生的巨噬细胞中高滴度生长。然而,最近有报道称,细胞蛋白SAMHD1会限制HIV-1在包括单核细胞衍生的巨噬细胞在内的髓系谱系人类细胞中的复制。在此我们表明,单核细胞衍生的巨噬细胞中SAMHD1的降解与嗜巨噬细胞的HIV-1毒株生长适度增强有关。用含有病毒蛋白X的水泡性口炎病毒糖蛋白假型化2型人类免疫缺陷病毒(HIV-2)颗粒处理靶巨噬细胞可诱导SAMHD1降解。对于未分化的单核细胞,HIV-2颗粒处理使未分化的单核细胞对嗜巨噬细胞的HIV-1毒株的生产性感染完全敏感。相比之下,未处理的单核细胞对HIV-1复制完全抗性。这些结果表明,SAMHD1在单核细胞衍生的巨噬细胞中对即使是嗜巨噬细胞的HIV-1毒株也有适度限制作用,而该蛋白在未分化的单核细胞中则能有效限制HIV-1复制。

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