ACTIVATION OF HUMAN MONOCYTE DERIVED MACROPHAGES WITH LIPOPOLYSACCHARIDE DECREASES HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION INVITRO AT THE LEVEL OF GENE-EXPRESSION
ACTIVATION OF HUMAN MONOCYTE DERIVED MACROPHAGES WITH LIPOPOLYSACCHARIDE DECREASES HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION INVITRO AT THE LEVEL OF GENE-EXPRESSION
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DOI：
10.1172/jci115337
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发表时间：
1991-08-01
影响因子：
15.9
通讯作者：
LOCKSLEY, RM
中科院分区：
文献类型：
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作者：
BERNSTEIN, MS;TONGSTARKSEN, SE;LOCKSLEY, RM
感染人免疫缺陷病毒-1（HIV-1）的T淋巴细胞的活化导致病毒复制增强，这部分是通过活化能够直接结合病毒长末端重复序列或LTR中序列的细胞NF-κ-B介导的。 与CD 4 + T细胞一起，巨噬细胞构成HIV-1感染的主要靶标。 然而，与淋巴细胞不同，单核吞噬细胞的刺激与细胞分裂和增殖无关。 用HIV-LTR-CAT构建体转染的人单核细胞衍生的巨噬细胞在用细菌脂多糖（LPS）刺激后表现出CAT活性的下调，所述细菌脂多糖（LPS）定位于与NF-κ-B结合位点不同的区域。 相反，新鲜单核细胞和前单核细胞U937细胞系均显示LPS上调HIV-LTR-CAT表达。 PMA诱导U937分化为非分裂表型后，LPS下调转染的HIV-LTR-CAT活性，与成熟巨噬细胞相似。 体外感染HIV-1的人单核细胞衍生的巨噬细胞在LPS中孵育后表现出病毒p24释放的减少，这与瞬时转染试验中发生的负调控相当。 控制HIV复制的因素可能在分裂和非分裂造血细胞中不同，并且可能有助于限制非分裂细胞中的病毒表达。
Activation of T lymphocytes infected with the human immunodeficiency virus-1 (HIV-1) results in enhancement of viral replication mediated in part by activation of cellular NF-kappa-B capable of binding directly to sequences in the viral long terminal repeat, or LTR. Together with CD4+ T cells, macrophages constitute a major target for infection by HIV-1. Unlike lymphocytes, however, stimulation of mononuclear phagocytes is not associated with cell division and proliferation. Human monocyte-derived macrophages transfected with HIV-LTR-CAT constructs demonstrated down-regulation of CAT activity after stimulation with bacterial lipopolysaccharide (LPS) that mapped to a region distinct from NF-kappa-B binding sites. In contrast, fresh monocytes and the promonocytic U937 cell line both demonstrated up-regulation of HIV-LTR-CAT expression by LPS. Differentiation of U937 by PMA to establish a nondividing phenotype resulted in down-regulation of transfected HIV-LTR-CAT activity by LPS similar to that in mature macrophages. Human monocyte-derived macrophages infected with HIV-1 in vitro demonstrated a decrease in viral p24 release after incubation in LPS that was comparable to the negative regulation that occurred in the transient transfection assays. Factors controlling HIV replication may differ in dividing and nondividing hematopoietic cells and may contribute to restricted viral expression in nondividing cells.