CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression

Area of Science:

• Veterinary Virology
• Immunology
• Molecular Biology

Background:

• Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant swine pathogen.
• CD163 is the essential cellular receptor for PRRSV, with scavenger receptor cysteine-rich domains 5-9 (SRCR5-9) mediating virus interaction.

Purpose of the Study:

• To develop and characterize monoclonal antibodies (mAbs) targeting the SRCR5-9 region of CD163 for PRRSV inhibition.
• To investigate the therapeutic and prophylactic potential of these mAbs against PRRSV.
• To elucidate the mechanism of antibody-mediated PRRSV inhibition and identify critical viral interaction sites.

Main Methods:

• Selection of mAbs 6E8 and 9A10 based on PRRSV inhibition in Porcine Alveolar Macrophages (PAMs) and Marc-145 cells.
• Assessment of mAb efficacy against various PRRSV strains and at different stages of infection (pre- and post-attachment).
• Analysis of CD163 transcription levels following antibody treatment and identification of conformational epitopes using site-directed mutagenesis.

Main Results:

• Both mAbs 6E8 and 9A10 effectively blocked PRRSV infection in a dose-dependent manner across different strains.
• Antibody treatment inhibited PRRSV infection and the NF-κB pathway, demonstrating both preventive and therapeutic potential.
• Antibody binding led to decreased CD163 transcription, potentially due to impaired CD163 cleavage, and identified critical residues (SXDVGXV in SRCR5 and Q in SRCR7) for PRRSV invasion.

Conclusions:

• Monoclonal antibodies targeting specific epitopes on CD163 provide a promising strategy for PRRSV prevention and treatment.
• Understanding the CD163-PRRSV interaction at the molecular level enables the development of novel antiviral approaches.
• These findings contribute to broader strategies for controlling PRRSV through receptor-targeted interventions.