Infection with a newly designed dual fluorescent reporter HIV-1 effectively identifies latently infected CD4+ T cells

eLife

Zhongsi Hong¹  Yanyan Yang²  Zhuanglin Dai²  Kai Deng³  Hongbo Gao³  Shujing Hu³  Jiacong Zhao³  Jinfeng Cai³  Xinyu Liang³ 

[1] Department of Infectious Diseases, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China;Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;

关键词: HIV-1;    latent infection;    cell model;    latency reversing agent;    Human;   

DOI  :  10.7554/eLife.63810

来源: eLife Sciences Publications, Ltd

【 摘 要 】

The major barrier to curing HIV-1 infection is a small pool of latently infected cells that harbor replication-competent viruses, which are widely considered the origin of viral rebound when antiretroviral therapy (ART) is interrupted. The difficulty in distinguishing latently infected cells from the vast majority of uninfected cells has represented a significant bottleneck precluding comprehensive understandings of HIV-1 latency. Here we reported and validated a newly designed dual fluorescent reporter virus, DFV-B, infection with which primary CD4+ T cells can directly label latently infected cells and generate a latency model that was highly physiological relevant. Applying DFV-B infection in Jurkat T cells, we generated a stable cell line model of HIV-1 latency with diverse viral integration sites. High-throughput compound screening with this model identified ACY-1215 as a potent latency reversing agent, which could be verified in other cell models and in primary CD4+ T cells from ART-suppressed individuals ex vivo. In summary, we have generated a meaningful and feasible model to directly study latently infected cells, which could open up new avenues to explore the critical events of HIV-1 latency and become a valuable tool for the research of AIDS functional cure.

【 授权许可】

CC BY