10.3389/fimmu.2019.02151.s001
Bingfeng Liu
Bingfeng
Liu
Xu Zhang
Xu
Zhang
Wanying Zhang
Wanying
Zhang
Liyang Wu
Liyang
Wu
Shuliang Jing
Shuliang
Jing
Weiwei Liu
Weiwei
Liu
Baijin Xia
Baijin
Xia
Fan Zou
Fan
Zou
Lijuan Lu
Lijuan
Lu
Xiancai Ma
Xiancai
Ma
Dalian He
Dalian
He
Qifei Hu
Qifei
Hu
Yiwen Zhang
Yiwen
Zhang
Kai Deng
Kai
Deng
Weiping Cai
Weiping
Cai
Xiaoping Tang
Xiaoping
Tang
Tao Peng
Tao
Peng
Hui Zhang
Hui
Zhang
Linghua Li
Linghua
Li
Data_Sheet_1_Lovastatin Inhibits HIV-1-Induced MHC-I Downregulation by Targeting Nef–AP-1 Complex Formation: A New Strategy to Boost Immune Eradication of HIV-1 Infected Cells.docx
Frontiers
2019
HIV-1
Nef
lovastatin
MHC-I
CD4
SERINC5
AP-1
immune surveillance
2019-09-11 06:50:38
Dataset
https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_Lovastatin_Inhibits_HIV-1-Induced_MHC-I_Downregulation_by_Targeting_Nef_AP-1_Complex_Formation_A_New_Strategy_to_Boost_Immune_Eradication_of_HIV-1_Infected_Cells_docx/9798242
<p>Current combined antiretroviral therapy (cART) mainly targets 3 of the 15 HIV proteins leaving many potential viral vulnerabilities unexploited. To purge the HIV-1 latent reservoir, various strategies including “shock and kill” have been developed. A key question is how to restore impaired immune surveillance. HIV-1 protein Nef has long been known to mediate the downregulation of cell-surface MHC-I and assist HIV-1 to evade the immune system. Through high throughput screening of Food and Drug Administration (FDA) approved drugs, we identified lovastatin, a statin drug, to significantly antagonize Nef to downregulate MHC-I, CD4, and SERINC5, and inhibit the intrinsic infectivity of virions. In addition, lovastatin boosted autologous CTLs to eradicate the infected cells and effectively inhibit the subsequent viral rebound in CD4<sup>+</sup> T-lymphocytes isolated from HIV-1-infected individuals receiving suppressive cART. Furthermore, we found that lovastatin inhibits Nef-induced MHC-I downregulation by directly binding with Nef and disrupting the Nef–AP-1 complex. These results demonstrate that lovastatin is a promising agent for counteracting Nef-mediated downregulation of MHC-I, CD4, and SERINC5. Lovastatin could potentially be used in the clinic to enhance anti-HIV-1 immune surveillance.</p>