ICAM-5/Telencephalin Is a Functional Entry Receptor for Enterovirus D68

Area of Science:

• Virology
• Neuroscience
• Cell Biology

Background:

• Enterovirus D68 (EV-D68) is a Picornaviridae family member increasingly linked to respiratory illness and acute flaccid myelitis.
• The cellular receptor for EV-D68 has remained unidentified, hindering understanding of its pathogenesis.

Purpose of the Study:

• To identify the cellular receptor for Enterovirus D68.
• To elucidate the role of this receptor in EV-D68 infection and pathogenesis.

Main Methods:

• Investigated the binding of EV-D68 to various cell types.
• Utilized soluble ICAM-5 fragments to inhibit viral replication.
• Employed ICAM-5 silencing and expression in permissive and non-permissive cells.

Main Results:

• Identified neuron-specific intercellular adhesion molecule 5 (ICAM-5/telencephalin) as a cellular receptor for EV-D68.
• Demonstrated specific and efficient binding of EV-D68 to ICAM-5.
• Showed that ICAM-5 mediates both sialic acid-dependent and -independent viral entry.
• Confirmed that ICAM-5 expression is critical for EV-D68 replication in permissive and non-permissive cells.

Conclusions:

• ICAM-5 is a key cellular receptor for EV-D68, crucial for viral entry and replication.
• The identification of ICAM-5 has significant implications for understanding EV-D68 pathogenesis, particularly in neurological disorders.
• This discovery may lead to the development of novel therapeutic strategies against EV-D68 infections.