Leno M, Hague B F, Teller R, Kindt T J
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
Virology. 1995 Nov 10;213(2):450-4. doi: 10.1006/viro.1995.0017.
Normal rabbit lymphocytes can be infected with HIV-1 although infection is much less efficient than in human lymphocytes. When peripheral blood mononuclear cells (PBMC) from rabbits transgenic for human CD4 (HuCD4) were exposed to HIV-1, enhanced infection and a rapid depletion of lymphocytes were observed. Cell death in the infected cultures occurred via apoptosis, but no similar effect was seen in nontransgenic rabbit PBMC cultures. Induction of apoptosis in HuCD4-expressing cells required virus replication; heat-inactivated virus or recombinant viral proteins had no effect on cell viability. Expression of the Fas antigen was increased in HIV-1-infected CD4+ rabbit lymphocytes. Characterization of the infected PBMC cultures revealed that apoptosis occurs both in HuCD4+ and HuCD4- cells, indicating that bystander cells are killed. These data define a requirement for HuCD4 in initiation, but not the spread, of HIV-1-induced apoptosis in rabbit PBMC and provide a model to probe mechanisms leading to lymphocyte depletion in HIV-1 infection.
正常兔淋巴细胞可被HIV-1感染，尽管感染效率远低于人类淋巴细胞。当将转人CD4（HuCD4）基因的兔外周血单个核细胞（PBMC）暴露于HIV-1时，可观察到感染增强以及淋巴细胞迅速耗竭。感染培养物中的细胞死亡通过凋亡发生，但在非转基因兔PBMC培养物中未观察到类似效应。在表达HuCD4的细胞中诱导凋亡需要病毒复制；热灭活病毒或重组病毒蛋白对细胞活力无影响。Fas抗原的表达在HIV-1感染的CD4+兔淋巴细胞中增加。对感染的PBMC培养物的特征分析表明，凋亡在HuCD4+和HuCD4-细胞中均发生，表明旁观者细胞被杀死。这些数据确定了HuCD4在兔PBMC中HIV-1诱导凋亡的起始而非传播中的需求，并提供了一个模型来探究导致HIV-1感染中淋巴细胞耗竭的机制。
