McEntee M F, Flexner C, Farzadegan H, Pitha P, Narayan O
Division of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Antimicrob Agents Chemother. 1993 Feb;37(2):360-2. doi: 10.1128/AAC.37.2.360.
We previously showed that simian immunodeficiency virus-infected macaque macrophages contacting uninfected CD4+ lymphocytes caused extensive cell fusion and synthesis of phlogistic cytokines. In this study, macaque macrophage cultures inoculated with SIVmac251 and treated simultaneously with 10 microM 3'-azidothymidine (AZT) became infected and produced small amounts of viral antigen (p27) but failed to fuse with CD4+ CEM174 cells. When AZT was added 1 to 3 days after virus inoculation, the infected cells caused fusion and the release of tumor necrosis factor and produced increasing amounts of p27. In contrast, neutralizing antibodies prevented infection when added at the time of virus inoculation, and they were much more effective than AZT in limiting virus replication, fusion cytopathic effect, and cytokine production when added up to 3 days postinoculation. Neutralizing antibodies may be more effective than AZT in reducing the virus load in the macrophage population and in preventing both cell fusion and the production of potentially pathogenic cytokines.
我们先前表明,感染猿猴免疫缺陷病毒的猕猴巨噬细胞与未感染的CD4+淋巴细胞接触会导致广泛的细胞融合和炎性细胞因子的合成。在本研究中,接种SIVmac251并同时用10 microM 3'-叠氮胸苷(AZT)处理的猕猴巨噬细胞培养物被感染并产生少量病毒抗原(p27),但未能与CD4+CEM174细胞融合。当在病毒接种后1至3天添加AZT时,受感染细胞导致融合并释放肿瘤坏死因子,并产生越来越多的p27。相比之下,中和抗体在病毒接种时添加可防止感染,并且在接种后3天内添加时,它们在限制病毒复制、融合细胞病变效应和细胞因子产生方面比AZT更有效。中和抗体在降低巨噬细胞群体中的病毒载量以及预防细胞融合和潜在致病细胞因子的产生方面可能比AZT更有效。