Highly active antiretroviral therapy (HAART) offers patients long-term suppression of HIV replication, but it does not cure the patients because of the long lasting latent HIV reservoir- one of the major obstacles in curing HIV infection. Reactivation of latent HIV has been under intensive investigation; however, no strategy has been developed to specifically reactivate latent HIV due to limited knowledge of how the latency is maintained. We propose to perform genome- wide knockout screening to identify the host factors that are essential for HIV latency maintenance and gain comprehensive insight into the mechanism. There has been no method for performing genome-wide loss-of-function screening in cultured cells until the appearance of four recent papers that described a CRISPR-Cas9-mediated genome-wide knockout screen. We have independently developed a similar approach to perform genome-wide screening to identify the host factors that are indispensable for WNV-induced cell death, and the results show that our method can identify target genes with high specificity. Thus, we are confident that we can identify the host factors systematically to gain comprehensive insight into the mechanism of how host factors facilitate HIV latency maintenance. We will test the identified genes in different J-Lat clones to identify the host factors that might reactivate latent HIV specifically and universally, which might lead to a new therapy to eradicate latent HIV reservoir.

Public Health Relevance

The proposed research is relevant to public health because the project aims to understand the mechanism of how host factors facilitate the maintenance of HIV latency. The knowledge gained from this project may lead to the development of a new therapy for HIV patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI124803-01
Application #
9136545
Study Section
AIDS Molecular and Cellular Biology Study Section (AMCB)
Program Officer
Kuo, Lillian S
Project Start
2016-07-01
Project End
2018-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$191,250
Indirect Cost
$66,250
Name
Texas Tech University
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
City
Lubbock
State
TX
Country
United States
Zip Code
79430