Potent inhibition of human immunodeficiency virus type 1 replication by conditionally replicating human immunodeficiency virus-based lentiviral vectors expressing envelope antisense mRNA
Potent inhibition of human immunodeficiency virus type 1 replication by conditionally replicating human immunodeficiency virus-based lentiviral vectors expressing envelope antisense mRNA
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DOI：
10.1089/10430340050143444
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发表时间：
2000-09-20
影响因子：
4.2
通讯作者：
Morgan, RA
中科院分区：
文献类型：
--
作者：
Mautino, MR;Morgan, RA
我们描述了一种基于HIV的慢病毒载体，其表达针对含有env序列的HIV-1 mRNA的1-kb反义mRNA。反义env mRNA（envAS）的表达不抑制用于包装载体的HIV-1辅助质粒表达的p24的合成，因为该辅助质粒在env基因中缺失。这允许产生高滴度的VSV-G假型慢病毒颗粒。在使用该载体转导的未选择的SupT 1细胞群的激发实验中，即使在高HIV-1感染剂量下，在长时间的体外培养中也观察到HIV-1复制的完全抑制。该载体对HIV-1复制的有效抑制与该载体向先前未转导的细胞的动员的低发生率相关。逃避抑制的野生型HIV-1的感染性被高度抑制，这表明该载体不仅由于其反义作用，而且还通过竞争对未感染细胞的抑制和动员来提供HIV-1的复制抑制。
We describe an HIV-based lentiviral vector that expresses a 1-kb antisense mRNA directed against the HIV-1 mRNAs containing env sequences. The expression of antisense env mRNAs (envAS) does not inhibit the synthesis of p24 expressed from the HIV-1 helper plasmid used to package the vector, as this helper has a deletion in the env gene. This allows the production of high-titer VSV-G pseudotyped lentiviral particles. In challenge experiments using unselected populations of SupT1 cells transduced with this vector, a complete inhibition of HIV-1 replication was observed for long periods of irt vitro culture, even at high HIV-1 infectious doses. The potent inhibition of HIV-1 replication by this vector correlated with a low occurrence of mobilization of the vector to previously untransduced cells. The infectivity of the wild-type HIV-1 that escapes inhibition was highly inhibited, suggesting that the vector is providing HIV-1 inhibition of replication not only due to its antisense effect but also by competing for encapsidation and mobilization to noninfected cells.