Application of CRISPR-Cas9 Gene Editing for HIV Host Factor Discovery and Validation

Human Immunodeficiency Virus (HIV) interacts with a wide array of host factors at each stage of its lifecycle to facilitate replication and circumvent the immune response. Identification and characterization of these host factors is critical for elucidating the mechanism of viral replication and for...

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Main Authors: William J. Cisneros, Daphne Cornish, Judd F. Hultquist
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Pathogens
Subjects:
Online Access:https://www.mdpi.com/2076-0817/11/8/891
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author William J. Cisneros
Daphne Cornish
Judd F. Hultquist
author_facet William J. Cisneros
Daphne Cornish
Judd F. Hultquist
author_sort William J. Cisneros
collection DOAJ
description Human Immunodeficiency Virus (HIV) interacts with a wide array of host factors at each stage of its lifecycle to facilitate replication and circumvent the immune response. Identification and characterization of these host factors is critical for elucidating the mechanism of viral replication and for developing next-generation HIV-1 therapeutic and curative strategies. Recent advances in CRISPR-Cas9-based genome engineering approaches have provided researchers with an assortment of new, valuable tools for host factor discovery and interrogation. Genome-wide screening in a variety of in vitro cell models has helped define the critical host factors that play a role in various cellular and biological contexts. Targeted manipulation of specific host factors by CRISPR-Cas9-mediated gene knock-out, overexpression, and/or directed repair have furthermore allowed for target validation in primary cell models and mechanistic inquiry through hypothesis-based testing. In this review, we summarize several CRISPR-based screening strategies for the identification of HIV-1 host factors and highlight how CRISPR-Cas9 approaches have been used to elucidate the molecular mechanisms of viral replication and host response. Finally, we examine promising new technologies in the CRISPR field and how these may be applied to address critical questions in HIV-1 biology going forward.
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spelling doaj.art-d0a1de02fb884ae4a00142230d05721d2023-12-02T00:08:13ZengMDPI AGPathogens2076-08172022-08-0111889110.3390/pathogens11080891Application of CRISPR-Cas9 Gene Editing for HIV Host Factor Discovery and ValidationWilliam J. Cisneros0Daphne Cornish1Judd F. Hultquist2Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USADivision of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USADivision of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USAHuman Immunodeficiency Virus (HIV) interacts with a wide array of host factors at each stage of its lifecycle to facilitate replication and circumvent the immune response. Identification and characterization of these host factors is critical for elucidating the mechanism of viral replication and for developing next-generation HIV-1 therapeutic and curative strategies. Recent advances in CRISPR-Cas9-based genome engineering approaches have provided researchers with an assortment of new, valuable tools for host factor discovery and interrogation. Genome-wide screening in a variety of in vitro cell models has helped define the critical host factors that play a role in various cellular and biological contexts. Targeted manipulation of specific host factors by CRISPR-Cas9-mediated gene knock-out, overexpression, and/or directed repair have furthermore allowed for target validation in primary cell models and mechanistic inquiry through hypothesis-based testing. In this review, we summarize several CRISPR-based screening strategies for the identification of HIV-1 host factors and highlight how CRISPR-Cas9 approaches have been used to elucidate the molecular mechanisms of viral replication and host response. Finally, we examine promising new technologies in the CRISPR field and how these may be applied to address critical questions in HIV-1 biology going forward.https://www.mdpi.com/2076-0817/11/8/891HIVhost factorsCRISPR-Cas9screeninggene editing
spellingShingle William J. Cisneros
Daphne Cornish
Judd F. Hultquist
Application of CRISPR-Cas9 Gene Editing for HIV Host Factor Discovery and Validation
Pathogens
HIV
host factors
CRISPR-Cas9
screening
gene editing
title Application of CRISPR-Cas9 Gene Editing for HIV Host Factor Discovery and Validation
title_full Application of CRISPR-Cas9 Gene Editing for HIV Host Factor Discovery and Validation
title_fullStr Application of CRISPR-Cas9 Gene Editing for HIV Host Factor Discovery and Validation
title_full_unstemmed Application of CRISPR-Cas9 Gene Editing for HIV Host Factor Discovery and Validation
title_short Application of CRISPR-Cas9 Gene Editing for HIV Host Factor Discovery and Validation
title_sort application of crispr cas9 gene editing for hiv host factor discovery and validation
topic HIV
host factors
CRISPR-Cas9
screening
gene editing
url https://www.mdpi.com/2076-0817/11/8/891
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