GS-CA1 and lenacapavir stabilize the HIV-1 core and modulate the core interaction with cellular factors.
GS-CA1 and lenacapavir stabilize the HIV-1 core and modulate the core interaction with cellular factors.
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DOI：
10.1016/j.isci.2021.103593
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发表时间：
2022-01-21
期刊：
影响因子：
5.8
通讯作者：
Diaz-Griffero F
中科院分区：
文献类型：
--
作者：
Selyutina A;Hu P;Miller S;Simons LM;Yu HJ;Hultquist JF;Lee K;KewalRamani VN;Diaz-Griffero F
HIV-1衣壳是抗病毒药物GS-CA 1和Lenacapavir（GS-6207）的靶点。我们研究了GS-CA 1和GS-6207抑制HIV-1感染的机制。GS-CA 1对HIV-1的抑制作用不需要CD 4 + T细胞中的CPSF 6。与加速HIV-1的脱壳的PF 74相反，GS-CA 1和GS-6207稳定核心。与PF 74不同，GS-CA 1允许核心进入细胞核，这与GS-CA 1在逆转录后抑制感染的事实一致。与PF 74不同，GS-CA 1不会在核斑点中解聚预先形成的CPSF 6复合物，这表明PF 74和GS-CA 1具有不同的作用机制。GS-CA 1稳定了HIV-1核心，可能是通过诱导核心中的构象转变;一致的是，携带N74 D的HIV-1核心在GS-CA 1存在下恢复了其结合CPSF 6的能力。我们发现GS-CA 1与HIV-1核心结合，改变其构象，稳定核心，从而防止病毒脱壳和感染。GS-CA 1和Lenacapavir（GS-6207）在感染期间稳定HIV-1核心GS-CA 1/GS-6207抑制HIV-1核心与宿主因子的相互作用GS-CA 1/GS-6207不分解核斑点中预先形成的CPSF 6复合物GS-CA 1/GS-6207影响HIV-1核心的动态表面生物科学;免疫学;病毒学
The HIV-1 capsid is the target for the antiviral drugs GS-CA1 and Lenacapavir (GS-6207). We investigated the mechanism by which GS-CA1 and GS-6207 inhibit HIV-1 infection. HIV-1 inhibition by GS-CA1 did not require CPSF6 in CD4+ T cells. Contrary to PF74 that accelerates uncoating of HIV-1, GS-CA1 and GS-6207 stabilized the core. GS-CA1, unlike PF74, allowed the core to enter the nucleus, which agrees with the fact that GS-CA1 inhibits infection after reverse transcription. Unlike PF74, GS-CA1 did not disaggregate preformed CPSF6 complexes in nuclear speckles, suggesting that PF74 and GS-CA1 have different mechanisms of action. GS-CA1 stabilized the HIV-1 core, possibly by inducing a conformational shift in the core; in agreement, HIV-1 cores bearing N74D regained their ability to bind CPSF6 in the presence of GS-CA1. We showed that GS-CA1 binds to the HIV-1 core, changes its conformation, stabilizes the core, and thereby prevents viral uncoating and infection. GS-CA1 and Lenacapavir (GS-6207) stabilizes the HIV-1 core during infection GS-CA1/GS-6207 inhibit the interaction of the HIV-1 core with host factors GS-CA1/GS-6207 do not disaggregate preformed CPSF6 complexes in nuclear speckles GS-CA1/GS-6207 affects the dynamic surface of the HIV-1 core Biological sciences; Immunology; Virology
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DOI：
10.1007/978-1-59745-170-3_5
发表时间：
2009
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Mbisa JL;Delviks-Frankenberry KA;Thomas JA;Gorelick RJ;Pathak VK
通讯作者：
Pathak VK
影响因子：
--
作者：
Selyutina A;Diaz-Griffero F
通讯作者：
Diaz-Griffero F
影响因子：
5.4
作者：
Buffone, Cindy;Martinez-Lopez, Alicia;Diaz-Griffero, Felipe
通讯作者：
Diaz-Griffero, Felipe
影响因子：
5.4
作者：
Shi, Jiong;Zhou, Jing;Whitby, Kevin
通讯作者：
Whitby, Kevin
影响因子：
5.4
作者：
Balasubramaniam, Muthukumar;Zhou, Jing;Dash, Chandravanu
通讯作者：
Dash, Chandravanu