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浆细胞样树突状细胞的低水平HIV感染:PDC成熟后细胞病变效应和细胞死亡的发生

Low-level HIV infection of plasmacytoid dendritic cells: onset of cytopathic effects and cell death after PDC maturation.

作者信息

Schmidt Barbara, Scott Iain, Whitmore Robert G, Foster Hillary, Fujimura Sue, Schmitz Juergen, Levy Jay A

机构信息

Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA 94143-0128, USA.

出版信息

Virology. 2004 Nov 24;329(2):280-8. doi: 10.1016/j.virol.2004.08.016.

DOI:10.1016/j.virol.2004.08.016
PMID:15518808
Abstract

Plasmacytoid dendritic cells (PDC), the natural type-1 interferon (IFN) producing cells, are part of the innate immune defense against human immunodeficiency virus (HIV). PDC numbers are reduced in advanced stages of infection. These cells can be infected in vivo by HIV since highly purified PDC showed evidence of infectious HIV. Moreover, when PDC derived from uninfected donors were exposed to high-titered HIV isolates, productive infection occurred although with low-level replication. Using real-time amplification, PDC and unstimulated CD4+ cells were found equally susceptible to HIV infection; however, HIV replication was considerably limited in the PDC. Virus replication was enhanced after PDC treatment with CD40L and antibodies against IFN-alpha, most likely reflecting the reduction in IFN-alpha activity. On maturation, the infected PDC showed multinuclear cell syncytia formation and death. These findings indicate that PDC can be reservoirs for HIV dissemination and that HIV infection of PDC can contribute to their decline.

摘要

浆细胞样树突状细胞(pDC)是天然产生1型干扰素(IFN)的细胞,是针对人类免疫缺陷病毒(HIV)的固有免疫防御的一部分。在感染的晚期,pDC数量会减少。这些细胞在体内可被HIV感染,因为高度纯化的pDC显示出感染性HIV的证据。此外,当从未感染供体获得的pDC暴露于高滴度HIV分离株时,尽管复制水平较低,但仍会发生 productive感染。使用实时扩增法发现,pDC和未刺激的CD4 +细胞对HIV感染同样敏感;然而,HIV在pDC中的复制受到相当大的限制。在用CD40L和抗IFN-α抗体处理pDC后,病毒复制增强,这很可能反映了IFN-α活性的降低。成熟时,受感染的pDC显示出多核细胞融合体的形成和死亡。这些发现表明,pDC可能是HIV传播的储存库,并且pDC的HIV感染可能导致其数量下降。

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