The neonatal Fc receptor (FcRn) is a pan-arterivirus receptor

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Arteriviruses infect various mammals, but their cellular entry mechanisms and host receptors remain largely unknown.
• Understanding arterivirus entry is crucial for controlling viral spread and emergence in different host species.

Purpose of the Study:

• To identify host factors essential for arterivirus cell entry.
• To investigate the role of the neonatal Fc receptor (FcRn) in arterivirus infection.
• To explore FcRn as a potential target for pan-arterivirus countermeasures.

Main Methods:

• Comparative genome-wide CRISPR-knockout screens were performed using multiple arteriviruses.
• Infection assays were conducted using various cell lines and arteriviruses, including FcRn and CD163 manipulation.
• Treatment with a pre-clinical anti-FcRn monoclonal antibody was used to assess therapeutic potential.

Main Results:

• The neonatal Fc receptor (FcRn) was identified as a critical pro-viral host factor for arterivirus entry.
• FcRn is required for the entry step of arterivirus infection and acts as a barrier to cross-species transmission.
• FcRn synergizes with CD163 to mediate arterivirus entry, and its overexpression can sensitize cells to infection.

Conclusions:

• The neonatal Fc receptor (FcRn) is a novel pan-arterivirus receptor.
• FcRn plays a significant role in arterivirus host tropism and cross-species infection.
• Targeting FcRn with antibodies presents a promising host-directed strategy for developing pan-arterivirus countermeasures.