Tackling HIV Persistence: Pharmacological versus CRISPR-Based Shock Strategies

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Retroviral pathogenesis involves integrating viral DNA into host genomes, forming proviruses.
• Retroviral latency, particularly in human immunodeficiency virus type 1 (HIV-1), explains treatment limitations and persistent reservoirs.
• Understanding latency is crucial for developing effective HIV-1 cure strategies.

Purpose of the Study:

• To discuss human immunodeficiency virus type 1 (HIV-1) latency and the formation of persistent viral reservoirs.
• To explore the "shock and kill" strategy for eliminating latent HIV-1.
• To present the application of clustered regularly interspaced palindromic repeats (CRISPR) and associated protein (Cas) systems in HIV-1 cure research.

Main Methods:

• Review of "shock and kill" pharmacological approaches to reactivate latent proviruses.
• Discussion of clustered regularly interspaced palindromic repeats (CRISPR) and associated protein (Cas) systems for HIV-1 gene reactivation.
• Comparative analysis of different HIV-1 cure strategies.

Main Results:

• HIV-1 latency leads to long-lasting viral reservoirs, hindering complete eradication.
• "Shock and kill" strategies aim to induce viral expression for immune system clearance.
• CRISPR-Cas systems offer a potential method to reactivate latent HIV-1 gene expression.

Conclusions:

• Effective HIV-1 cure strategies must address latent viral reservoirs.
• Both pharmacological "shock and kill" and CRISPR-Cas based approaches present distinct benefits and drawbacks.
• Further research is needed to optimize these strategies for HIV-1 eradication.