De Rossi A, Ometto L, Roncella S, D'Andrea E, Menin C, Calderazzo F, Rowe M, Ferrarini M, Chieco-Bianchi L
Institute of Oncology, University of Padova, Padua, Italy.
Virology. 1994 Jan;198(1):234-44. doi: 10.1006/viro.1994.1026.
Interactions between HIV-1 and EBV were studied in HIV-1-infected EBV-positive lymphoblastoid B cells. Following in vitro exposure of B cells to HIV-1, the number of infected cells reached a plateau (25-35%) in approximately 20 days and remained fairly stable thereafter, despite the presence of infectious virus in culture supernatants. HIV-1-positive (gp120+) were separated from HIV-1-negative (gp120-) cells, and the two fractions were further characterized for EBV antigens, bcl-2 expression, and growth capacity in vitro. Compared to gp120- cells, EBNA 1, EBNA 2, and LMP 1 were down-regulated, and the episomal form of EBV-DNA was dramatically decreased in the gp120+ cells. When plated in culture gp120+, but not gp120-, cells died; BZLF1 antigen was not expressed, thus ruling out a reactivation of the EBV lytic cycle. Cytofluorometric, morphological, and molecular analyses disclosed that gp120+ cell death was due instead to apoptosis; evidence of bcl-2 down-regulation in these cells was consistent with this finding. gp120+ cell apoptosis contributed to keeping the level of HIV-1-infected cells at a steady state in the unfractionated culture, where persistent infection was maintained by HIV-1 transmission to B cells newly arising from the proliferation of HIV-1-uninfected cells.
在感染了HIV-1的EBV阳性淋巴母细胞样B细胞中研究了HIV-1与EBV之间的相互作用。在体外将B细胞暴露于HIV-1后，感染细胞的数量在大约20天内达到平台期（25%-35%），此后尽管培养上清液中存在感染性病毒，但该数量仍保持相当稳定。将HIV-1阳性（gp120+）细胞与HIV-1阴性（gp120-）细胞分离，并对这两个部分进一步进行EBV抗原、bcl-2表达及体外生长能力的鉴定。与gp120-细胞相比，gp120+细胞中EBNA 1、EBNA 2和LMP 1表达下调，EBV-DNA的游离形式显著减少。当接种到培养基中时，gp120+细胞而非gp120-细胞死亡；未检测到BZLF1抗原表达，因此排除了EBV裂解周期的重新激活。细胞荧光分析、形态学分析及分子分析表明，gp120+细胞死亡是由凋亡所致；这些细胞中bcl-2下调的证据与这一发现一致。在未分离的培养物中，gp120+细胞凋亡有助于使HIV-1感染细胞的水平保持稳定状态，在该培养物中，HIV-1通过传播至由未感染HIV-1的细胞增殖新产生的B细胞来维持持续感染。
