Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4 + T cells from HIV-1 infection

Zhepeng Liu; Shuliang Chen; Xu Jin; Qiankun Wang; Kongxiang Yang; Chenlin Li; Qiaoqiao Xiao; Panpan Hou; Shuai Liu; Shaoshuai Wu; Wei Hou; Yong Xiong; Chunyan Kong; Xixian Zhao; Li Wu; Chunmei Li; Guihong Sun; Deyin Guo

doi:10.1186/s13578-017-0174-2

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Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4 + T cells from HIV-1 infection

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Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4 + T cells from HIV-1 infection

Zhepeng Liu, Shuliang Chen, Xu Jin, Qiankun Wang, Kongxiang Yang, Chenlin Li, Qiaoqiao Xiao, Panpan Hou, Shuai Liu, Shaoshuai Wu, …

Cell & bioscience, Vol.7(1), pp.47-47

2017

DOI: 10.1186/s13578-017-0174-2

PMCID: PMC5591563

PMID: 28904745

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Abstract

The main approach to treat HIV-1 infection is combination antiretroviral therapy (cART). Although cART is effective in reducing HIV-1 viral load and controlling disease progression, it has many side effects, and is expensive for HIV-1 infected patients who must remain on lifetime treatment. HIV-1 gene therapy has drawn much attention as studies of genome editing tools have progressed. For example, zinc finger nucleases (ZFN), transcription activator like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 have been utilized to successfully disrupt the HIV-1 co-receptors CCR5 or CXCR4, thereby restricting HIV-1 infection. However, the effects of simultaneous genome editing of CXCR4 and CCR5 by CRISPR-Cas9 in blocking HIV-1 infection in primary CD4 T cells has been rarely reported. Furthermore, combination of different target sites of CXCR4 and CCR5 for disruption also need investigation. In this report, we designed two different gRNA combinations targeting both CXCR4 and CCR5, in a single vector. The CRISPR-sgRNAs-Cas9 could successfully induce editing of CXCR4 and CCR5 genes in various cell lines and primary CD4 T cells. Using HIV-1 challenge assays, we demonstrated that CXCR4-tropic or CCR5-tropic HIV-1 infections were significantly reduced in - and -modified cells, and the modified cells exhibited a selective advantage over unmodified cells during HIV-1 infection. The off-target analysis showed that no non-specific editing was identified in all predicted sites. In addition, apoptosis assays indicated that simultaneous disruption of CXCR4 and CCR5 in primary CD4 T cells by CRISPR-Cas9 had no obvious cytotoxic effects on cell viability. Our results suggest that simultaneous genome editing of CXCR4 and CCR5 by CRISPR-Cas9 can potentially provide an effective and safe strategy towards a functional cure for HIV-1 infection.

AIDS

CCR5 and CXCR4 simultaneous

HIV-1

CRISPR-Cas9

Details

Title: Subtitle: Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4 + T cells from HIV-1 infection
Creators: Zhepeng Liu - School of Basic Medical Sciences, Wuhan University, Wuhan, 430072 People's Republic of China
Shuliang Chen - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, USA
Xu Jin - Guangxi Center for Disease Control and Prevention, Nanning, Guangxi People's Republic of China
Qiankun Wang - School of Basic Medical Sciences, Wuhan University, Wuhan, 430072 People's Republic of China
Kongxiang Yang - College of Life Science, Wuhan University, Wuhan, People's Republic of China
Chenlin Li - School of Basic Medical Sciences, Wuhan University, Wuhan, 430072 People's Republic of China
Qiaoqiao Xiao - School of Basic Medical Sciences, Wuhan University, Wuhan, 430072 People's Republic of China
Panpan Hou - College of Life Science, Wuhan University, Wuhan, People's Republic of China
Shuai Liu - School of Basic Medical Sciences, Wuhan University, Wuhan, 430072 People's Republic of China
Shaoshuai Wu - School of Basic Medical Sciences, Wuhan University, Wuhan, 430072 People's Republic of China
Wei Hou - School of Basic Medical Sciences, Wuhan University, Wuhan, 430072 People's Republic of China
Yong Xiong - Zhongnan Hospital, Wuhan University, Wuhan, People's Republic of China
Chunyan Kong - School of Basic Medical Sciences, Wuhan University, Wuhan, 430072 People's Republic of China
Xixian Zhao - School of Basic Medical Sciences, Wuhan University, Wuhan, 430072 People's Republic of China
Li Wu - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, USA
Chunmei Li - School of Medicine (Shenzhen), Sun Yat-sen University, Guangzhou, 510080 People's Republic of China
Guihong Sun - School of Basic Medical Sciences, Wuhan University, Wuhan, 430072 People's Republic of China
Deyin Guo - School of Medicine (Shenzhen), Sun Yat-sen University, Guangzhou, 510080 People's Republic of China
Resource Type: Journal article
Publication Details: Cell & bioscience, Vol.7(1), pp.47-47
DOI: 10.1186/s13578-017-0174-2
PMID: 28904745
PMCID: PMC5591563
NLM abbreviation: Cell Biosci
ISSN: 2045-3701
eISSN: 2045-3701
Publisher: England
Grant note: name: China National Special Research Program of Major Infectious Diseases, award: 2014ZX10001003; name: Hubei Provincial Science & Technology Innovation Team Grant, award: 2012FFA043; DOI: 10.13039/501100001809, name: Natural Science Foundation of China, award: 81401659; DOI: 10.13039/501100002858, name: China Postdoctoral Science Foundation, award: 2015T80838; name: China Postdoctoral Science Foundation (CN), award: 2014M560622
Language: English
Date published: 2017
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001114802771

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