HIV-1 gp41 ectodomain enhances Cryptococcus neoformans binding to HBMEC.

Area of Science:

• Neuroscience
• Infectious Diseases
• Immunology

Background:

• Cryptococcus neoformans infections are increasing, especially in immunocompromised individuals.
• C. neoformans causes meningoencephalitis by targeting the brain.
• Human brain microvascular endothelial cells (HBMEC) form the blood-brain barrier.

Purpose of the Study:

• To investigate the role of HIV-1 gp41 protein in C. neoformans invasion of HBMEC.
• To identify the functional domain of gp41 involved in enhancing invasion.
• To validate findings in an animal model.

Main Methods:

• Utilized HBMEC to model the blood-brain barrier.
• Employed peptide mapping to define the functional domain of gp41.
• Used recombinant gp41 protein (gp41-I90) for experiments.
• Conducted experiments in a mouse model.

Main Results:

• HIV-1 gp41 protein significantly enhanced C. neoformans invasion of HBMEC.
• The functional domain of gp41 was localized to a.a. 579-611.
• Enhancement of C. neoformans binding to HBMEC was strain-independent.
• The observed enhancement was replicated in a mouse model.

Conclusions:

• HIV-1 gp41 ectodomain directly enhances C. neoformans invasion of HBMEC.
• A similar invasion mechanism, potentially involving actin reorganization or membrane activation, may be utilized by both HIV-1 and C. neoformans.
• Findings provide insights into cryptococcal meningoencephalitis pathogenesis in HIV-1 patients.