Characterization of human immunodeficiency virus type 1 replication in immature and mature dendritic cells reveals dissociable cis- and trans-infection
Characterization of human immunodeficiency virus type 1 replication in immature and mature dendritic cells reveals dissociable cis- and trans-infection
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DOI：
10.1128/jvi.01081-07
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发表时间：
2007-10-01
影响因子：
5.4
通讯作者：
Wu, Li
中科院分区：
文献类型：
--
作者：
Dong, Chunsheng;Janas, Alicia M.;Wu, Li
树突状细胞（DC）通过反式和顺式感染途径将人类免疫缺陷病毒1型（HIV-1）传递给CD 4（+）T细胞;然而，关于这些途径的相对效率以及它们是否相互依赖知之甚少。在这里，我们比较顺式和反式感染的HIV-1介导的未成熟的DC（iDC）和成熟的DC（mDC），使用复制能力和单周期的HIV-1。单核细胞衍生的iDC通过脂多糖（LPS）、肿瘤坏死因子α（TNF-α）和CD 40配体（CD 40 L）分化成各种类型的mDC。iDC和CD 40 L诱导的mDC对HIV-1感染敏感，并介导有效的病毒传播至CD 4（+）T细胞。虽然HIV-1顺式感染在TNF-α诱导的mDC中部分受到限制，在LPS诱导的mDC中被彻底阻断，但这些细胞有效地促进了HIV-1对CD 4（+）T细胞的反式感染。使用病毒DNA和整合的实时PCR定量，在逆转录和整合后的水平上鉴定LPS诱导的mDC中HIV-1感染的后限制。此外，核转染DC与HIV-1前病毒DNA证实，受损的基因表达的LPS诱导的mDC是负责HIV-1感染后的限制。我们的研究结果表明，在体内不同的DC亚群可能差异有助于通过解离顺式和反式感染的HIV-1传播。
Dendritic cells (DCs) transmit human immunodeficiency virus type 1 (HIV-1) to CD4(+) T cells through the trans- and cis-infection pathways; however, little is known about the relative efficiencies of these pathways and whether they are interdependent. Here we compare cis- and trans-infections of HIV-1 mediated by immature DCs (iDCs) and mature DCs (mDCs), using replication-competent and single-cycle HIV-1. Monocyte-derived iDCs were differentiated into various types of mDCs by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), and CD40 ligand (CD40L). iDCs and CD40L-induced mDCs were susceptible to HIV-1 infection and mediated efficient viral transmission to CD4(+) T cells. Although HIV-1 cis-infection was partially restricted in TNF-alpha-induced mDCs and profoundly blocked in LPS-induced mDCs, these cells efficiently promoted HIV-1 trans-infection of CD4(+) T cells. The postentry restriction of HIV-1 infection in LPS-induced mDCs was identified at the levels of reverse transcription and postintegration, using real-time PCR quantification of viral DNA and integration. Furthermore, nucleofection of DCs with HIV-1 proviral DNA confirmed that impaired gene expression of LPS-induced mDCs was responsible for the postentry restriction of HIV-1 infection. Our results suggest that various DC subsets in vivo may differentially contribute to HIV-1 dissemination via dissociable cis- and trans- infections.