摘要
HIV-1相关肾病是一种能够在未合适地利用抗逆转录病毒疗法加以治疗的非洲裔HIV阳性患者体内产生的肾病。尽管经过多年的广泛研究。人们仍不清楚来自HIV阳性患者的并不表达主要的HIV-1CD4受体的肾上皮细胞是如何被HIV-1感染的。
Studies have shown that podocytes and renal tubular epithelial cells from patients with HIV-associated nephropathy (HIVAN) express HIV-1 transcripts, suggesting that productive infection of renal epithelial cells precipitates development of HIVAN. However, podocytes and renal tubular epithelial cells do not express CD4 receptors, and it is unclear how these cells become productively infected in vivo. We investigated the mechanisms underlying the infection by HIV-1 of podocytes cultured from the urine of children with HIVAN. We observed low-level productive infection on exposure of these cells to primary cell-free HIV-1 supernatants. However, envelope-defective recombinant HIV-1 did not infect the renal epithelial cell lines. Moreover, treatment of podocytes to inhibit endocytic transport or dynamin activity or remove cell surface heparan sulfate proteoglycans reduced infection efficiency. Transfection of CD4− 293T cells with a cDNA expression library developed from a podocyte cell line derived from a child with HIVAN led to the identification of TNF-α as a possible mediator of HIV-1 infection. Overexpression of transmembrane TNF-α in cultured CD4− renal tubular epithelial cells, 293T cells, and HeLa cells enabled the infection of these cells; exposure to soluble TNF-α did not. Immunohistochemistry showed TNF-α expression in podocytes of renal sections from children with HIVAN. Furthermore, we found that TNF-α enhanced NF-κB activation and integration of HIV-1 into the podocyte DNA. Finally, inhibition of dynamin activity blocked TNF-α-mediated infection. These data establish a role for transmembrane TNF-α in facilitating the viral entry and integration of HIV-1 into the DNA of renal epithelial cells.
出处
《现代生物医学进展》
CAS
2017年第8期I0001-I0001,共1页
Progress in Modern Biomedicine
关键词
HIV-1
肾细胞
受体
感染
鉴定
逆转录病毒
上皮细胞
肾病
HIV nephropathy
children
cytokines
pediatric nephrology
podocyte
renal tubular epithelial cells