Inhibiting Glycan Degradation Prevents HIV-Induced Inflammaging and Cognitive Impairment

Area of Science:

• Neuroscience
• Immunology
• Glycobiology

Background:

• Chronic viral infections, like HIV, are linked to premature aging and cognitive impairment.
• The precise mechanisms behind HIV-associated cognitive impairment (HIV-CI) are not fully understood.

Purpose of the Study:

• To identify key molecular contributors to HIV-associated cognitive impairment (HIV-CI).
• To investigate the role of glycan degradation in HIV-CI and explore potential therapeutic interventions.

Main Methods:

• Analysis of glycan changes (sialic acid, galactose) in human cohorts with HIV.
• Utilizing a humanized mouse model and Eco-HIV model for in vivo studies.
• Pharmacological inhibition of glycan degradation using sialidase inhibitors.

Main Results:

• Degradative glycan changes, indicative of premature aging, were prevalent in individuals with HIV-CI, especially females.
• These changes correlated with poorer cognitive function in people living with HIV.
• Sialidase inhibitors mitigated HIV-induced inflammation, immune activation, aging, and memory deficits in animal models.

Conclusions:

• Pro-inflammatory glycan degradation is a significant factor in HIV-associated cognitive impairment.
• Targeting glycan degradation with protective therapies offers a promising strategy to combat inflammation, premature aging, and cognitive decline in HIV and potentially other viral infections.