Hazan Uriel, Romero Ignacio A, Cancello Raffaella, Valente Susana, Perrin Virginie, Mariot Virginie, Dumonceaux Julie, Gerhardt Cindy C, Strosberg A Donny, Couraud Pierre-Olivier, Pietri-Rouxel France
CNRS UPR 0415 and, INSERM U380, Institut Cochin de Génétique Moléculaire, 75014 Paris, France.
FASEB J. 2002 Aug;16(10):1254-6. doi: 10.1096/fj.01-0947fje. Epub 2002 Jun 21.
The concept that adipocytes belong to an essential endocrine system with some characteristics of immune cells has recently emerged. The aim of this paper is to present evidence of the expression of CD4, CXCR4, and CCR5 receptors by human adipocytes and to test whether adipose cells support HIV entry. Primary human preadipocytes were cultured and differentiated in vitro. Expression of the three receptors on preadipocytes and adipocytes was demonstrated by reverse transcriptase-polymerase chain reaction, immunocytochemical, and immunohistochemical analysis. Infection of adipose cells to HIV-1 was then investigated. The measurement of the viral p24 antigen in preadipocyte culture medium showed an increase of p24 levels between 24 and 72 h postexposure and then a progressive decrease to reach a low level at 10-15 days. Ten days after the infection test, supernatant of preadipocytes contained infectious particles able to infect the susceptible T-CD4 CEM cell line. The expression of viral proteins by adipocytes was confirmed using a fusion test. The presence of viral DNA was exhibited by gag-specific polymerase chain reaction, supporting the hypothesis of HIV-1 X4- and R5-virus entry in preadipocytes. Adipose cells represent the first cell type that does not belong to the immune system expressing all specific HIV receptors and may represent new HIV-1 target cells.
脂肪细胞属于具有某些免疫细胞特征的重要内分泌系统这一概念最近才出现。本文旨在提供人类脂肪细胞表达CD4、CXCR4和CCR5受体的证据,并测试脂肪细胞是否支持HIV进入。对原代人前脂肪细胞进行体外培养和分化。通过逆转录聚合酶链反应、免疫细胞化学和免疫组织化学分析证明了前脂肪细胞和脂肪细胞上三种受体的表达。然后研究了脂肪细胞对HIV-1的感染情况。在前脂肪细胞培养基中测量病毒p24抗原,结果显示暴露后24至72小时p24水平升高,随后逐渐下降,在10至15天时降至低水平。感染测试10天后,前脂肪细胞的上清液中含有能够感染易感T-CD4 CEM细胞系的感染性颗粒。使用融合试验证实了脂肪细胞中病毒蛋白的表达。通过gag特异性聚合酶链反应显示了病毒DNA的存在,支持了HIV-1 X4和R5病毒进入前脂肪细胞的假说。脂肪细胞是第一种不属于免疫系统但表达所有特异性HIV受体的细胞类型,可能代表新的HIV-1靶细胞。