Valentin Antonio, Pavlakis George N
Human Retrovirus Section, BRL, National Cancer Institute-Frederick, MD 21702, USA.
Anticancer Res. 2003 May-Jun;23(3A):2071-5.
We have reported the presence of a CD4+ subpopulation of Natural Killer cells (NK) in humans. These cells also express HIV coreceptors CCR5 or CXCR4 and are infectable by HIV-1. Infection is productive and persistent in vitro and in vivo. Infected people under therapy have evidence of viral DNA in their NK pool. In vitro experiments show that the NK compartment is important for virus propagation, since HIV-1 growth is significantly reduced in PBMC depleted of NK cells. This reduction was observed for both R5 and X4 molecular clones of HIV-1. In addition, evidence is presented demonstrating that infected NK cells are killed less efficiently by the virus as compared to T cells. This is reminiscent of macrophage infection, where the virus-infected cells survive for long periods of time. Therefore, few infected NK cells may contribute significantly to the infectious virus produced in vitro. These results further underscore the importance of NK infection for understanding pathogenic mechanisms leading to AIDS, as well as the various reservoirs and sanctuaries for HIV upon antiretroviral treatment.
我们已经报道了人类中存在一种自然杀伤细胞(NK)的CD4 +亚群。这些细胞还表达HIV共受体CCR5或CXCR4,并且可被HIV-1感染。感染在体外和体内都是有活性且持续存在的。接受治疗的感染者在其NK细胞库中有病毒DNA的证据。体外实验表明,NK细胞区室对病毒传播很重要,因为在耗尽NK细胞的外周血单核细胞(PBMC)中,HIV-1的生长显著降低。对于HIV-1的R5和X4分子克隆均观察到这种降低。此外,有证据表明,与T细胞相比,被感染的NK细胞被病毒杀死的效率较低。这让人联想到巨噬细胞感染,其中病毒感染的细胞可以长时间存活。因此,少数被感染的NK细胞可能对体外产生的感染性病毒有显著贡献。这些结果进一步强调了NK细胞感染对于理解导致艾滋病的致病机制以及抗逆转录病毒治疗后HIV的各种储存库和庇护所的重要性。