GP4-specific neutralizing antibodies might be a driving force in PRRSV evolution.

Area of Science:

• Virology
• Immunology
• Animal Health

Background:

• The European porcine reproductive and respiratory syndrome virus (PRRSV) envelope glycoprotein GP4 has a variable neutralizing epitope.
• This epitope is known to be susceptible to antibody-mediated selection in vitro.

Purpose of the Study:

• To investigate the in vivo evolution of the GP4 neutralizing epitope during PRRSV infection in the presence of neutralizing antibodies.
• To determine the role of neutralizing antibodies in selecting for antibody-escape PRRSV variants.

Main Methods:

• Vaccination of pigs followed by inoculation with Lelystad virus (LV) to create antibody-mediated selective pressure.
• Isolation and characterization of neutralizing antibody-escape PRRSV variants.
• Confirmation of antibody-escape by neutralization assays using autologous sera and a GP4-specific monoclonal antibody (mAb).

Main Results:

• Nine antibody-escape variants were isolated from pigs under selective pressure.
• Six variants had amino acid substitutions in the GP4 epitope, conferring resistance to neutralization by a GP4-specific mAb and autologous sera.
• These six variants originated from pigs with early antibody responses against the epitope.
• The remaining three variants lacked epitope substitutions and remained sensitive to neutralization, isolated from pigs without early epitope-specific antibodies.

Conclusions:

• Amino acid substitutions within the GP4 neutralizing epitope can abolish antibody recognition.
• Neutralizing antibodies are likely responsible for selecting PRRSV variants resistant to neutralization due to mutations in the GP4 epitope.
• Neutralizing antibodies may drive the rapid evolution of the GP4 neutralizing epitope in European PRRSV strains.