HIV-1 Mediated Cortical Actin Disruption Mirrors ARP2/3 Defects Found in Primary T Cell Immunodeficiencies

Area of Science:

• Immunology
• Cell Biology
• Virology

Background:

• Cortical actin dynamics are crucial for CD4+ T cell migration and morphology.
• HIV-1 infection is known to impair CD4+ T cell function, but the underlying mechanisms affecting cell movement remain unclear.

Approach:

• Investigated HIV-1-induced morphological changes in primary CD4+ T cells using ultrastructural and time-lapse imaging.
• Examined the role of the actin cytoskeleton by using chemical inhibitors, specifically targeting the ARP2/3 complex.
• Assessed the impact of a ΔNef HIV-1 variant on cellular morphology.

Key Points:

• HIV-1 infection induces at least four distinct morphological alterations in CD4+ T cells due to cortical cytoskeleton disruption.
• A ΔNef HIV-1 virus partially rescued the dysfunctional phenotype and restored normal cell shape.
• The ARP2/3 inhibitor CK-666 mimicked three of the four observed HIV-1-induced morphologies, implicating ARP2/3 in the process.

Conclusions:

• HIV-1 infection profoundly disrupts CD4+ T cell cytoskeleton and morphology, phenocopying certain primary immunodeficiencies.
• Targeting ARP2/3 function and cortical actin integrity presents a novel therapeutic avenue for eradicating HIV-1 infected cells.