Enzyme Hinders HIV-1 Tat Viral Transport and Real-Time Measured with Nanopores,ACS Sensors

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Enzyme Hinders HIV-1 Tat Viral Transport and Real-Time Measured with Nanopores
ACS Sensors ( IF 8.2 ) Pub Date : 2021-09-16 , DOI: 10.1021/acssensors.1c01717
Han Wang _{1,

2,

3} , Wenli Huang ₄ , Yunjiao Wang _{1,

2} , Wei Li _{1,

2} , Qianshan Liu _{1,

2} , Bohua Yin ₁ , Liyuan Liang _{1,

2} , Deqiang Wang _{1,

2} , Xiyun Guan ₅ , Liang Wang _{1,

2,

3}

Affiliation

HIV-1 Tat protein, an intercellular transporter with a determinant function of delivering “information-rich” molecules in viral multiplication, was tryptic-hydrolyzed and real-time single molecule-monitored in a transmembrane pore. The electrokinetic studies revealed the catalytic and inhibitory effects on enzymatic digestion associated with Ca²⁺ and Cu²⁺ ions, respectively, in response to binding interactions with trypsin. Our strategy permits accurate and distinguishable sensing of Ca²⁺ and Cu²⁺via an enzyme assay. In addition, considering the closer mimic of the real situation of HIV spread, measurements in the serum and on cells were also investigated. Transmembrane current measurements together with fluorescence microscopy imaging indicated the potential to perturb the Tat transport in the serum environment and on cells. Because the involved Tat proteolysis should prevent the occurrence of viral delivery, the presented method probably enables efficient hindrance to HIV-1 infection, in complementary to current traditional treatments.

中文翻译：

酶阻碍 HIV-1 Tat 病毒运输并使用纳米孔进行实时测量

HIV-1 Tat 蛋白是一种细胞间转运蛋白，具有在病毒增殖中传递“信息丰富”分子的决定性功能，在跨膜孔中被胰蛋白酶水解和实时单分子监测。电动研究揭示了对分别与 Ca ²⁺和 Cu ²⁺离子相关的酶消化的催化和抑制作用，以响应与胰蛋白酶的结合相互作用。我们的策略允许准确和可区分的传感 Ca ²⁺和 Cu ²⁺通过酶测定。此外，考虑到更接近真实的 HIV 传播情况，还研究了血清和细胞上的测量值。跨膜电流测量与荧光显微镜成像一起表明有可能扰乱血清环境和细胞上的 Tat 转运。由于所涉及的 Tat 蛋白水解应防止病毒传递的发生，因此所提出的方法可能能够有效阻止 HIV-1 感染，与当前的传统治疗相辅相成。

更新日期：2021-10-22

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