MASSIVE COVERT INFECTION OF HELPER T-LYMPHOCYTES AND MACROPHAGES BY HIV DURING THE INCUBATION PERIOD OF AIDS
MASSIVE COVERT INFECTION OF HELPER T-LYMPHOCYTES AND MACROPHAGES BY HIV DURING THE INCUBATION PERIOD OF AIDS
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DOI：
10.1038/362359a0
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发表时间：
1993-03-25
期刊：
影响因子：
64.8
通讯作者：
HAASE, AT
中科院分区：
文献类型：
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作者：
EMBRETSON, J;ZUPANCIC, M;HAASE, AT
动物和人类慢病毒通过建立隐匿性感染来逃避宿主防御，最终因病毒基因表达激活导致细胞累积性损失而引发疾病[1 - 5]。我们运用原位聚合酶链反应双标记法[6,7]来确定人类免疫缺陷病毒（HIV）在患者淋巴结中潜伏感染了多少CD4 +淋巴细胞，以及被感染的细胞群是否足够大，足以解释因病毒基因持续激活以及对抗原起反应的细胞损耗而导致的免疫耗竭。我们发现从感染早期到晚期，整个淋巴系统中存在数量极多的潜伏感染的CD4 +淋巴细胞和巨噬细胞，并证实了[8 - 14]HIV与滤泡树突状细胞的细胞外结合。当细胞迁移穿过淋巴滤泡时，滤泡树突状细胞可能会将感染传播给其他细胞。潜伏感染的淋巴细胞和巨噬细胞构成了一个足够大的细胞内储存库，最终可能导致艾滋病中大部分的免疫耗竭，这是在开发有效治疗方法和保护性疫苗时必须解决的一个难题。
ANIMAL and human lentiviruses elude host defences by establishing covert infections and eventually cause disease through cumulative losses of cells that die with activation of viral gene expression1-5. We used polymerase chain reaction in situ double-label methods6,7 to determine how many CD4+ lymphocytes are latently infected by human immunodeficiency virus (HIV) in patient lymph nodes and whether the pool of infected cells is large enough to account for immune depletion through continual activation of viral gene expression and attrition of cells responding to antigens. We discovered an extraordinarily large number of latently infected CD4+ lymphocytes and macrophages throughout the lymphoid system from early to late stages of infection, and confirmed8-14 the extracellular association of HIV with follicular dendritic cells. Follicular dendritic cells may transmit infection to cells as they migrate through lymphoid follicles. Latently infected lymphocytes and macrophages constitute an intracellular reservoir large enough ultimately to contribute to much of the immune depletion in AIDS, and represent a difficult problem that must be resolved in developing effective treatments and protective vaccine.