干扰素-γ的一种肿瘤坏死因子-α诱导型启动子变体可加速人类免疫缺陷病毒1型感染个体中CD4 + T细胞的耗竭。

A tumor necrosis factor-alpha-inducible promoter variant of interferon-gamma accelerates CD4+ T cell depletion in human immunodeficiency virus-1-infected individuals.

作者信息

An Ping, Vlahov David, Margolick Joseph B, Phair John, O'Brien Thomas R, Lautenberger James, O'Brien Stephen J, Winkler Cheryl A

机构信息

Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702, USA.

出版信息

J Infect Dis. 2003 Jul 15;188(2):228-31. doi: 10.1086/376455. Epub 2003 Jul 9.

DOI:10.1086/376455

PMID:12854077

Abstract

A polymorphism, -179G/T, in the promoter of the interferon (IFN)-gamma gene (IFNG) confers differential tumor necrosis factor-alpha (TNF-alpha) inducibility to the IFNG promoter. The rarer allele, -179T, but not -179G, is inducible by TNF-alpha. We investigated the effects of IFNG -179G/T on AIDS pathogenesis. In 298 African American human immunodeficiency virus (HIV)-1 seroconverters, the IFNG -179G/T genotype was associated with accelerated progression to CD4 <200 and AIDS-1993, a finding suggesting that IFNG -179T is a risk factor for AIDS progression, as measured by CD4 cell count. It is possible that increased IFN-gamma production induced by TNF-alpha when -179T is present causes CD4 cell depletion by apoptosis.

摘要

干扰素（IFN）-γ基因（IFNG）启动子中的一种多态性-179G/T赋予IFNG启动子不同的肿瘤坏死因子-α（TNF-α）诱导性。较罕见的等位基因-179T可被TNF-α诱导，而-179G则不能。我们研究了IFNG -179G/T对艾滋病发病机制的影响。在298名非裔美国人类免疫缺陷病毒（HIV）-1血清转化者中，IFNG -179G/T基因型与进展至CD4<200及1993年定义的艾滋病加速相关，这一发现表明，以CD4细胞计数衡量，IFNG -179T是艾滋病进展的一个风险因素。当存在-179T时，TNF-α诱导的IFN-γ产生增加，有可能通过凋亡导致CD4细胞耗竭。