Genome editing of PSIP1 gene encoding LEDGF/p75 protects TZM_bl GFP cells from HIV-1 infection
DOI:
https://doi.org/10.62051/yc7e4q47Keywords:
PSIP1, LEDGF, HIV-1, CRISPR/Cas, TZM_bl GFP cells, Infectivity assay, Western blot, Flow cytometry, Immunofluorescence.Abstract
Gene therapy is a good way to cure HIV permanently. Human immunodeficiency virus (HIV-1) infected cells depend on host-cell factors. LEDGF/p75 is a co-factor encoded by the PSIP1 gene and it interacts with HIV integrase to help the virus bind to host cells genome. If the PSIP1 gene is knocked out in the TZM-bI GFP cell line using CRISPR/Cas technology, the amount of HIV DNA integrated into the cell will be reduced due to the inability of HIV integrase to efficiently bind and integrate into the transcriptionally active regions of the host cell chromatin. The change in infectivity was observed by fluorescence microscopy and flow cytometry. The results show that KO PSIP1 may inhibit HIV infectivity. More experiments are needed to prove the reliability of this result.
Downloads
References
[1] Liu, Zhepeng et al. “Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4+ T cells from HIV-1 infection.” Cell & bioscience vol. 7 47. 9 Sep. 2017, doi:10.1186/s13578-017-0174-2
[2] Qi J, Ding C, Jiang X, Gao Y. Advances in developing CAR T-Cell therapy for HIV cure. Frontiers in Immunology [Internet]. 2020 Mar 10;11. Available from: https://doi.org/10.3389/fimmu.2020.00361
[3] LEDGF: A Leukemia-Specific Target | Blood | American Society of Hematology,ashpublications.org/blood/article/131/1/4/107677/LEDGF-a-leukemia-specific-target. Accessed 21 June 2024.
[4] Blokken J, De Rijck J, Christ F, Debyser Z. Protein–protein and protein–chromatin interactions of LEDGF/p75 as novel drug targets. Drug Discovery Today Technologies [Internet]. 2017 Jun 1;24:25–31. Available from: https://www.sciencedirect.com/science/article/pii/S1740674916300476?via=ihub
[5] Cillo AR, Mellors JW. Which therapeutic strategy will achieve a cure for HIV-1? Current Opinion in Virology [Internet]. 2016 Jun 1;18:14–9. Available from: https://www.sciencedirect.com/science/article/pii/S1879625716300050?via%3Dihub
[6] Ciuffi A, Diamond TL, Hwang Y, Marshall HM, Bushman FD. Modulating target site selection during human immunodeficiency virus DNA IntegrationIn vitrowith an engineered tethering factor. Human Gene Therapy [Internet]. 2006 Sep 1;17(9):960–7. Available from: https://doi.org/10.1089/hum.2006.17.960
[7] Kain SR, Kitts P. Expression and detection of Green Fluorescent Protein (GFP). In: Humana Press eBooks [Internet]. 2003. p. 305–24. Available from: https://doi.org/10.1385/0-89603-481-x:305
[8] Liedtke V, Schröder C, Roggenbuck D, Weiss R, Stohwasser R, Schierack P, et al. LEDGF/p75 Is Required for an Efficient DNA Damage Response. International Journal of Molecular Sciences [Internet]. 2021 May 30 [cited 2024 Mar 21];22(11):5866. Available from: https://pubmed.ncbi.nlm.nih.gov/34070855/
[9] Anderson AM, Tyor WR, Mulligan MJ, Waldrop-Valverde D, Lennox JL, Letendre SL. Measurement of Human Immunodeficiency Virus p24 Antigen in Human Cerebrospinal Fluid With Digital Enzyme-Linked Immunosorbent Assay and Association With Decreased Neuropsychological Performance. Clinical Infectious Diseases [Internet]. 2018 Jan 29;67(1):137–40. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005050/#:~:text=The%20HIV%20p24%20antigen%20is
[10] Benchling. Lab Pod 2. Biology Software, [2024, 06, 21]. Available from: https://benchling.com
Downloads
Published
Conference Proceedings Volume
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
