Clinical Scorecard: Occludin's Role in Protecting Against HIV and Ischemic Stroke

At a Glance

Key Highlights

• Occludin regulates blood–brain barrier permeability and innate immune responses influencing susceptibility of brain pericytes to HIV infection.
• Occludin silencing disrupts interferon-stimulated gene expression and mitochondrial antiviral signalling, leading to increased HIV replication and worsened ischaemic stroke outcomes.
• Mitochondrial dysfunction linked to occludin loss impairs antiviral responses and exacerbates cerebrovascular injury in HIV infection.

Guideline-Based Recommendations

Diagnosis

• Consider cerebrovascular risk assessment in people living with HIV even under effective ART with viral suppression.
• Evaluate blood–brain barrier integrity and mitochondrial function as potential markers in HIV-associated neurological complications.

Management

• Maintain and potentially enhance occludin expression/function to protect BBB integrity and improve innate immune responses.
• Address mitochondrial dysfunction as a therapeutic target to mitigate HIV-related cerebrovascular disease.

Monitoring & Follow-up

• Monitor viral loads in critical organs and neurological status in HIV patients at risk for stroke.
• Assess markers of mitochondrial bioenergetics and autophagy in research or specialized clinical settings.

Risks

• Persistent cerebrovascular risk despite ART due to mechanisms beyond viral replication.
• Increased susceptibility of pericytes to HIV infection with occludin dysfunction leading to BBB disruption and neuroinflammation.

Patient & Prescribing Data

People living with HIV, including those with controlled viral loads on ART

Therapeutic strategies enhancing occludin function and mitochondrial health may provide dual benefits in reducing HIV replication and improving stroke outcomes.

Clinical Best Practices

• Recognize the role of occludin beyond structural BBB function as an active modulator of innate immunity in HIV infection.
• Incorporate mitochondrial health assessment in understanding and managing HIV-associated neurological complications.
• Use animal models such as Eco-HIV-infected occludin-deficient mice to study pathophysiology and test interventions targeting occludin and mitochondrial pathways.

References

• Torices et al. Occludin modulates HIV and ischaemic stroke response via the mitochondrial antiviral signalling pathway