Modulation of HIV-1 infectivity by MAPK, a virion-associated kinase
Modulation of HIV-1 infectivity by MAPK, a virion-associated kinase
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DOI：
10.1093/emboj/17.9.2607
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发表时间：
1998-05-01
期刊：
影响因子：
11.4
通讯作者：
Stevenson, M
中科院分区：
文献类型：
--
作者：
Jacqué, JM;Mann, A;Stevenson, M
人类免疫缺陷病毒1型（HIV-1）感染细胞导致逆转录复合物的形成，其中合成病毒核酸。逆转录复合物从细胞膜的有效脱离和随后的核转位需要逆转录复合物组分被病毒体相关激酶磷酸化。在本研究中，我们鉴定了病毒粒子相关激酶为丝裂原活化蛋白激酶（MAPK/ERK）。经密度梯度分离，MAPK而不是其活化激酶MEK与病毒粒子共沉淀。在病毒生产细胞中表达组成型活性但非激酶失活的MEK 1能够反式激活病毒体相关的MAPK。促分裂原佛波醇肉豆蔻酸酯（PMA）反式刺激病毒体相关的MAPK活性增加病毒感染性，相反，MAPK级联的特异性抑制剂抑制病毒体相关的MAPK显著损害病毒感染性，这些研究证明了宿主细胞MAPK信号转导途径对HIV-1感染早期步骤的调节。
Infection of a cell by human immunodeficiency virus type 1 (HIV-1) results in the formation of a reverse transcription complex in which viral nucleic acids are synthesized. Efficient disengagement of the reverse transcription complex from the cell membrane and subsequent nuclear translocation require phosphorylation of reverse transcription complex components by a virion-associated kinase. In this study, we identify the virion-associated kinase as mitogen-activated protein kinase (ERK/MAPK), Upon density gradient fractionation, MAPK, but not its activating kinase MEK, co-sedimented with viral particles. Expression of a constitutively active, but not kinase-inactive, MEK1 in virus producer cells was able to activate virion-associated MAPK in trans. Stimulation of virion-associated MAPK activity in trans by the mitogen phorbol myristate acetate (PMA) increased viral infectivity, Conversely, suppression of virion-associated MAPK by specific inhibitors of the MAPK cascade markedly impaired viral infectivity, These studies demonstrate regulation of an early step in HIV-1 infection by the host cell MAPK signal transduction pathway.