Efficacy of antiretroviral agents against murine replication-competent retrovirus infection in human cells

Efficacy of antiretroviral agents against murine replication-competent retrovirus infection in human cells
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DOI:
10.1128/jvi.73.10.8813-8816.1999
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发表时间:
1999-10-01
影响因子:
5.4
通讯作者:
Otto, E
Otto, E
中科院分区:
医学2区
文献类型:
--
作者:
Powell, SK;Artlip, M;Otto, E

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用于基因治疗的逆转录病毒载体被设计为最小化复制能力逆转录病毒(RCR)的发生;然而,载体衍生的RCR可能在患者中建立感染。由于抗逆转录病毒药物的疗效可能受到病毒、宿主细胞和药物之间相互作用的影响,因此评价了5种常用抗逆转录病毒药物抑制人细胞中鼠白血病病毒(MLV)衍生RCR复制的能力。获得的结果表明,核苷类似物齐多夫定和双脱氧肌苷与蛋白酶抑制剂茚地那韦的组合有效地抑制MLV衍生的RCR在三种人细胞系中的复制。此外,发现MLV衍生的RCR对核苷类似物拉米夫定和司他夫定具有固有的耐药性,这表明即使在替代病毒骨架中,赋予人类免疫缺陷病毒1型对核苷类似物耐药性的突变也具有相同的效果。
Retroviral vectors for gene therapy are designed to minimize the occurrence of replication-competent retrovirus (RCR); nonetheless, it is possible that a vector-derived RCR could establish an infection in a patient. Since the efficacy of antiretroviral agents can be impacted by interactions between virus, host cell, and drug, five commonly used antiretroviral drugs were evaluated for their abilities to inhibit the replication of a murine leukemia virus (MLV)-derived RCR in human cells. The results obtained indicate that the combination of nucleoside analogs zidovudine and dideoxyinosine with the protease inhibitor indinavir effectively inhibits MLV-derived RCR replication in three human cell lines. In addition, MLV-derived RCR was found to be inherently resistant to the nucleoside analogs lamivudine and stavudine, suggesting that mutations conferring resistance to nucleoside analogs in human immunodeficiency virus type 1 have the same effect even in an alternative viral backbone.