HIV and SIV Envelope Glycoproteins Interact with Glycolipids and Lipids

Area of Science:

• Virology
• Biochemistry
• Cell Biology

Background:

• Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) are lentiviruses that cause significant global health challenges.
• Viral envelope glycoproteins are crucial for mediating virus entry into host cells.
• The precise molecular interactions governing HIV/SIV attachment and entry are still under investigation.

Purpose of the Study:

• To investigate the binding interactions of HIV-1, HIV-2, and SIV envelope glycoproteins with various ceramide species.
• To characterize the specificity and biophysical nature of these interactions.
• To explore the potential role of these interactions in viral infectivity and pathogenesis.

Main Methods:

• Molecular binding assays using radiolabeled viral glycoproteins (¹²⁵I-gp) and immobilized or thin-layer chromatography (TLC)-separated lipids (galactosylceramide [GalCer], glucosylceramide [GlcCer], lactosylceramide [LacCer], ceramide).
• Specificity assessment through dose-dependent inhibition with immune and non-immune sera and control protein (¹²⁵I-IgG).
• Physicochemical assays involving monomolecular films (Langmuir films) of glycolipids/lipids as a cell membrane model to measure surface pressure changes upon addition of viral glycoproteins.

Main Results:

• HIV-1, HIV-2, and SIV envelope glycoproteins physically interact with GalCer, GlcCer, LacCer, and ceramide.
• These interactions are specific, dose-dependent, saturable, and inhibited by immune sera but not non-immune sera or unrelated proteins.
• Physicochemical assays confirmed interactions, showing increased surface pressure of lipid films upon addition of viral glycoproteins.

Conclusions:

• HIV and SIV envelope glycoproteins exhibit specific binding to a range of ceramides, including GalCer, GlcCer, LacCer, and ceramide.
• These interactions may serve as alternative attachment receptors, facilitating infection of CD4-low or CD4-negative cells.
• The identified interactions could also contribute to pathogenesis by modulating host cell signaling pathways.