Adenovirus type 37 uses sialic acid as a cellular receptor

Area of Science:

• Virology
• Cell Biology
• Biochemistry

Background:

• Two cellular receptors, coxsackievirus-adenovirus receptor (CAR) and major histocompatibility complex class I alpha2 (MHC-I alpha2), are known for adenovirus attachment.
• MHC-I alpha2 is proposed as a receptor for subgenus C adenoviruses in the absence of CAR, while CAR interacts with most adenovirus subgenera except B.

Purpose of the Study:

• To investigate the cellular receptors utilized by adenovirus type 37 (Ad37) for cell attachment.
• To identify alternative or novel receptor moieties for Ad37 beyond CAR and MHC-I alpha2.

Main Methods:

• Ad37 attachment assays using CAR-expressing and non-expressing cells (CHO).
• Enzyme treatments (neuraminidase, protease) to assess the role of sialic acid and glycoproteins.
• Comparison of Ad37 binding to sialic acid-deficient (Lec2) and proficient (Pro-5) cell lines.
• Lectins and specific neuraminidases to determine sialic acid linkage type (alpha(2-->3) vs. alpha(2-->6)).
• Fluorescent-focus assay to evaluate Ad37 replication after neuraminidase treatment.

Main Results:

• Ad37 attachment was not dependent on CAR expression.
• Neuraminidase treatment significantly reduced Ad37 attachment, indicating sialic acid involvement.
• Ad37 binding was significantly stronger to sialic acid-expressing cells compared to deficient cells.
• Protease sensitivity suggested the receptor is a glycoprotein, not a ganglioside.
• Ad37 preferentially binds to alpha(2-->3)-linked sialic acid, not alpha(2-->6)-linked.

Conclusions:

• Adenovirus type 37 (Ad37) does not utilize CAR or MHC-I alpha2 for cell attachment.
• Sialic acid, specifically alpha(2-->3)-linked sialic acid on glycoproteins, serves as a novel receptor for Ad37.
• This discovery expands the understanding of adenovirus-host cell interactions and receptor diversity.