Stevenson M, Iversen P L
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68105.
J Gen Virol. 1989 Oct;70 ( Pt 10)(Pt 10):2673-82. doi: 10.1099/0022-1317-70-10-2673.
The ability of poly(L-lysine)-conjugated and methylphosphonate-modified synthetic human immunodeficiency virus type 1 (HIV-1) antisense oligodeoxyribonucleotides to protect susceptible host cells from the cytopathic effects of HIV-1 infection was studied. The abundance of viral antigens in oligomer-treated cultures indicated that the oligomers did not significantly affect viral infectivity. Similarly, no significant effects on relative viral RNA accumulation were apparent. The presence of poly(L-lysine)-modified oligomer complementary to the HIV-1 splice donor site resulted in a significant reduction in the production of viral structural proteins and virus titre in infected cultures. In addition, these cells were protected from HIV-1-mediated cytopathic effects while the other cultures rapidly succumbed to the cytotoxic effects of HIV-1 infection. The presence of poly(L-lysine)-conjugated oligomer resulted in the establishment of a persistent HIV-1 infection characterized by a highly productive virus infection in the absence of cell death while treatment of persistently infected cells with phorbol ester resulted in renewed cytopathicity. These results demonstrate the ability of synthetic antisense oligonucleotides to protect susceptible host cells from the cytopathic effects of HIV-1 infection.
研究了聚（L-赖氨酸）缀合且甲基膦酸酯修饰的合成人免疫缺陷病毒1型（HIV-1）反义寡脱氧核糖核苷酸保护易感宿主细胞免受HIV-1感染细胞病变效应的能力。在经寡聚物处理的培养物中病毒抗原的丰度表明，这些寡聚物并未显著影响病毒感染性。同样，对相对病毒RNA积累也没有明显的显著影响。与HIV-1剪接受体位点互补的聚（L-赖氨酸）修饰寡聚物的存在，导致受感染培养物中病毒结构蛋白的产生和病毒滴度显著降低。此外，这些细胞受到保护免受HIV-1介导的细胞病变效应，而其他培养物则迅速死于HIV-1感染的细胞毒性效应。聚（L-赖氨酸）缀合寡聚物的存在导致建立了持续性HIV-1感染，其特征是在无细胞死亡的情况下病毒感染高效进行，而用佛波酯处理持续感染的细胞则导致重新出现细胞病变。这些结果证明了合成反义寡核苷酸保护易感宿主细胞免受HIV-1感染细胞病变效应的能力。
