Tackling HIV Persistence: Pharmacological Versus CRISPR-Based Shock Strategies

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2018 Mar 30

PMID 29596334

Citations 18

Authors

Gilles Darcis

Atze T Das

Ben Berkhout

Affiliations

Soon will be listed here.

Abstract

Jan Svoboda studied aspects of viral latency, in particular with respect to disease induction by avian RNA tumor viruses, which were later renamed as part of the extended retrovirus family. The course of retroviral pathogenesis is intrinsically linked to their unique property of integrating the DNA copy of the retroviral genome into that of the host cell, thus forming the provirus. Retroviral latency has recently become of major clinical interest to allow a better understanding of why we can effectively block the human immunodeficiency virus type 1 (HIV-1) in infected individuals with antiviral drugs, yet never reach a cure. We will discuss HIV-1 latency and its direct consequence-the formation of long-lasting HIV-1 reservoirs. We next focus on one of the most explored strategies in tackling HIV-1 reservoirs-the "shock and kill" strategy-which describes the broadly explored pharmacological way of kicking the latent provirus, with subsequent killing of the virus-producing cell by the immune system. We furthermore present how the clustered regularly interspaced palindromic repeats (CRISPR) and associated protein (Cas) system can be harnessed to reach the same objective by reactivating HIV-1 gene expression from latency. We will review the benefits and drawbacks of these different cure strategies.

Citing Articles

Navigating Latency-Inducing Viral Infections: Therapeutic Targeting and Nanoparticle Utilization.

Vasukutty A, Jang Y, Han D, Park H, Park I Biomater Res. 2024; 28:0078.

PMID: 39416703 PMC: 11480834. DOI: 10.34133/bmr.0078.

Targeting Viral Transcription for HIV Cure Strategies.

Izquierdo-Pujol J, Puertas M, Martinez-Picado J, Moron-Lopez S Microorganisms. 2024; 12(4).

PMID: 38674696 PMC: 11052381. DOI: 10.3390/microorganisms12040752.

Gesicles packaging dCas9-VPR ribonucleoprotein complexes can combine with vorinostat and promote HIV proviral transcription.

Fisher M, Chaudhry W, Campbell L Mol Ther Methods Clin Dev. 2024; 32(1):101203.

PMID: 38390557 PMC: 10881426. DOI: 10.1016/j.omtm.2024.101203.

Targeted shock-and-kill HIV-1 gene therapy approach combining CRISPR activation, suicide gene tBid and retargeted adenovirus delivery.

Klinnert S, Schenkel C, Freitag P, Gunthard H, Pluckthun A, Metzner K Gene Ther. 2023; 31(3-4):74-84.

PMID: 37558852 PMC: 10940146. DOI: 10.1038/s41434-023-00413-1.

HIV-1 Infection of Long-Lived Hematopoietic Precursors In Vitro and In Vivo.

Renelt S, Schult-Dietrich P, Baldauf H, Stein S, Kann G, Bickel M Cells. 2022; 11(19).

PMID: 36230931 PMC: 9562211. DOI: 10.3390/cells11192968.

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