Kulka M, Aurelian L
Department of Pharmacology and Experimental Therapeutics University of Maryland School of Medicine, Baltimore 21201, USA.
Antisense Res Dev. 1995 Winter;5(4):243-9. doi: 10.1089/ard.1995.5.243.
Replication-defective adenovirus p259A caused a 400-fold increase in the sequence-specific antiherpetic activity of oligo(nucleoside methylphosphonate) (ONMP) IE4,5SA. Herpes simplex virus type 1 (HSV-1) growth was not inhibited in cells exposed to p259A in the absence of IE4,5SA or in cells cotreated with IE4,5SA and heated (10 minutes, 90 degrees C) p259A virus. Fluorescent microscopy of Vero cells treated with BODIPY-conjugated IE4,5SA revealed intracellular localization within endocytic-like vesicles with minimal cytoplasmic and intranuclear distribution. Diffuse staining over the entire cell was observed in cell cotreated with the BODIPY-conjugated IE4,5SA and p259A virus. This effect was not observed in cells cotreated with the BODIPY-conjugated ONMP and heated p259A virus. We interpret these findings to indicate that p259A augments IE4,5SA antiherpetic activity presumably via its ability to increase ONMP uptake and release from endocytic-like vesicles.
复制缺陷型腺病毒p259A使寡聚（核苷甲基膦酸酯）（ONMP）IE4,5SA的序列特异性抗疱疹活性提高了400倍。在没有IE4,5SA的情况下，单纯疱疹病毒1型（HSV-1）在暴露于p259A的细胞中生长未受抑制，或者在与IE4,5SA和加热（10分钟，90摄氏度）的p259A病毒共同处理的细胞中生长也未受抑制。用BODIPY偶联的IE4,5SA处理的Vero细胞的荧光显微镜检查显示，其在内吞样小泡内的细胞内定位，细胞质和核内分布极少。在用BODIPY偶联的IE4,5SA和p259A病毒共同处理的细胞中，观察到整个细胞弥漫性染色。在用BODIPY偶联的ONMP和加热的p259A病毒共同处理的细胞中未观察到这种效应。我们将这些发现解释为表明p259A可能通过其增加ONMP从内吞样小泡摄取和释放的能力来增强IE4,5SA的抗疱疹活性。
