Adenovirus type 37 binds to cell surface sialic acid through a charge-dependent interaction

Area of Science:

• Virology
• Molecular Biology
• Biochemistry

Background:

• Most adenoviruses utilize the coxsackie-adenovirus receptor (CAR) for cellular entry.
• Adenovirus types 8, 19a, and 37, responsible for epidemic keratoconjunctivitis, employ sialic acid as a primary receptor.
• The high isoelectric point of these adenovirus fiber knob domains suggests a role for charge in receptor interaction.

Purpose of the Study:

• To investigate the role of charge in the interaction between specific adenovirus types and sialic acid.
• To elucidate the mechanism by which adenovirus types 8, 19a, and 37 bind to sialic acid on cell surfaces.

Main Methods:

• Assessed cell membrane interactions of positively charged adenovirus knobs with sialic acid.
• Examined the sensitivity of viral and knob interactions with sialic acid to ionic strength.
• Investigated the inhibitory effects of negatively charged molecules on viral binding.
• Utilized homology modeling to predict the surface charge of adenovirus knob domains.

Main Results:

• Positively charged adenovirus knobs demonstrated a requirement for sialic acid for efficient cell membrane interactions.
• Viral and knob binding to sialic acid were sensitive to changes in ionic strength, indicating charge-dependent interactions.
• Sulfated glycosaminoglycans inhibited virion binding in a charge-dependent, non-specific manner.
• The interaction capability of adenovirus knobs with sialic acid correlated with their predicted surface charge.

Conclusions:

• Adenovirus types 8, 19a, and 37 utilize a charge-based mechanism for binding to sialic acid.
• This charge mechanism is crucial for the interaction between the Ad37 fiber knob and sialic acid.
• The findings provide significant evidence for electrostatic interactions in adenovirus-sialic acid binding.