The B-oligomer of pertussis toxin inhibits human immunodeficiency virus type 1 replication at multiple stages
The B-oligomer of pertussis toxin inhibits human immunodeficiency virus type 1 replication at multiple stages
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DOI：
10.1128/jvi.74.18.8767-8770.2000
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发表时间：
2000-09-01
影响因子：
5.4
通讯作者：
Bukrinsky, M
中科院分区：
文献类型：
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作者：
Alfano, M;Pushkarsky, T;Bukrinsky, M
我们最近证明百日咳毒素（PTX-B）的结合亚单位（B-寡聚体）使CCR 5失活，并抑制R5人类免疫缺陷病毒1型（HIV-1）株进入活化的原代T淋巴细胞（M.阿尔法诺等人，J. Exp. 190：597 - 605，1999）。我们现在提出的证据表明，PTX-B也影响HIV-1复制的后期步骤。虽然PTX-B抑制由R5诱导的融合，但不抑制由X4包膜诱导的融合，它阻断了用R5、X4假型化的重组HIV-1颗粒甚至鼠白血病病毒或水疱性口炎病毒包膜感染T细胞。当新的感染被齐杜定抑制时，它也抑制了感染的外周血单核细胞培养物中的HIV-1 RNA合成，并减少了由HIV-1长末端重复序列（LTR）控制的荧光素酶报告基因的Tat依赖性表达。令人惊讶的是，PTX-B不影响巨细胞病毒启动子的表达，也不降低LTR启动子的基础（Tat非依赖性）表达。这些结果表明，PTX-B抑制HIV-1感染的病毒复制的入口和postentry阶段，postentry活动特别影响转录或稳定性的Tat刺激的HIV-1 mRNA。
We have recently demonstrated that the binding subunit (B-oligomer) of pertussis toxin (PTX-B) deactivates CCR5 and inhibits entry of R5 human immunodeficiency virus type 1 (HIV-1) strains in activated primary T lymphocytes (M. Alfano et al., J. Exp. Med. 190:597-605, 1999). We now present evidence that PTX-B also affects a postentry step of HIV-1 replication. While PTX-B inhibited fusion induced by R5 but not that induced by X4 envelopes, it blocked infection of T cells with recombinant HIV-1 particles pseudotyped with R5, X4, and even murine leukemia virus or vesicular stomatitis virus envelopes. It also suppressed HIV-1 RNA synthesis in cultures of infected peripheral blood mononuclear cells when new infections had been inhibited by zidoudine, and it reduced Tat-dependent expression of the luciferase reporter gene controlled by the HIV-1 long terminal repeat (LTR). Surprisingly, PTX-B did not affect expression from the cytomegalovirus promoter, nor did it reduce the basal (Tat-independent) expression from the LTR promoter. These results indicate that PTX-B inhibits HIV-1 infection at both the entry and the postentry stages of viral replication, with the postentry activity specifically affecting transcription or stability of Tat-stimulated HIV-1 mRNAs.