CounterAKTing HIV: Toward a "Block and Clear" Strategy?

Area of Science:

• Molecular Biology
• Virology
• Immunology

Background:

• Protein kinase B (Akt) regulates essential cellular processes like survival, metabolism, growth, and proliferation.
• Akt is a key target for viral pathogens, notably Human Immunodeficiency Virus type 1 (HIV-1).
• HIV-1 proteins activate the PI3K/Akt pathway, promoting viral infection progression.

Purpose of the Study:

• To investigate the role of the PI3K/Akt pathway in HIV-1 pathogenesis.
• To explore the potential of targeting Akt as a therapeutic strategy against HIV-1.
• To evaluate Akt inhibitors in combination with latency-inducing agents for HIV-1 reservoir reduction.

Main Methods:

• Analysis of Akt pathway activation by HIV-1 proteins.
• Assessment of Akt's role in viral entry, latency, reactivation, cell survival, and spread.
• Evaluation of Akt inhibitors in preclinical models of HIV-1 infection.

Main Results:

• HIV-1 proteins activate the PI3K/Akt pathway, contributing to viral pathogenesis.
• Targeting Akt shows potential to inhibit viral entry, latency, and cell-to-cell spread.
• Akt inhibition may improve immune microenvironment and reduce HIV reservoir size.
• Combination therapy with Akt inhibitors and latency agents could enhance infected cell clearance.

Conclusions:

• The PI3K/Akt pathway is a critical regulator in HIV-1 pathogenesis.
• Targeting Akt presents a promising therapeutic avenue for controlling HIV-1 infection.
• A "block and clear" strategy combining Akt inhibitors with latency inducers may reduce the HIV reservoir.