Junction adhesion molecule is a receptor for reovirus.

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Virus attachment to host cells dictates viral tropism and disease progression.
• Reovirus serotypes exhibit distinct tropisms within the murine nervous system and varying capacities to induce apoptosis.
• The viral attachment protein sigma1 binds to unknown receptors, controlling these cellular phenotypes.

Purpose of the Study:

• To identify the specific cellular receptor for reovirus serotypes 1 and 3.
• To elucidate the role of this receptor in viral tropism, infection, and induction of apoptosis.
• To understand the signaling pathways initiated by reovirus-receptor interactions.

Main Methods:

• Expression cloning was employed to identify the reovirus receptor.
• Direct binding assays were performed to confirm the interaction between viral protein sigma1 and the identified receptor.
• NF-kappaB activation and apoptosis assays were conducted to assess the functional consequences of receptor ligation.

Main Results:

• Junction adhesion molecule (JAM), an integral tight junction protein, was identified as a functional reovirus receptor.
• JAM directly binds to the reovirus sigma1 protein, enabling infection of previously nonpermissive cells.
• Ligation of JAM by reovirus is essential for the activation of NF-kappaB and the subsequent induction of apoptosis.

Conclusions:

• Junction adhesion molecule (JAM) serves as a critical cell-surface receptor for reoviruses.
• Reovirus interaction with JAM is a key determinant of cell-type specific tropism.
• Reovirus binding to JAM initiates intracellular signaling cascades leading to NF-kappaB activation and apoptosis.