Event Title First Global Alliance for Research on Avian Diseases (GARAD) Conference
Session Title Unknown
Event Date & Time On Tue, 30 Jun 2015 at 16:07:00 - 15:20:00
Venue Edmond J. Safra Lecture Theatre
Abstract Title Polymerase stuttering: a previously unrecognized molecular mechanism contributing to antigenic variation in infectious bursal disease virus
Authors Sebastien M. SOUBIES
Affiliations French Agency for Food, Environment and Occupational Health Safety (Anses), Avian and Rabbit Virology and Parasitology Unit (VIPAC), 22440 Ploufragan, France
Abstract Content

Infectious bursal disease virus (IBDV, avibirnavirus, Birnaviridae) is a major pathogen in poultry production. IBDV serotype 1 targets the chicken bursa of Fabricius and infects B cells, resulting in mortality and/or immunosuppression. Vaccine control of IBDV mainly relies on humoral immunity elicited by VP2, IBDV capsid protein, which variations are therefore important to understand.

To study the evolution of IBDV VP2 under immune pressure, a cell culture-adapted IBDV strain was propagated in vitro in the presence of a neutralizing anti-VP2 monoclonal antibody (mAb). An escape mutant (EM6) was isolated. Sequencing of its genome revealed an amino acid (aa) insertion in one of the most exposed loops of the VP2 projected domain. Comparison with its parent virus revealed that the insertion was likely due to polymerase stuttering, a mechanism previously observed in several RNA viruses, notably influenza, but not in IBDV.

Reverse genetics was used to create the same insertion in the genetic background of the Cu1 IBDV strain. The resulting recombinant virus indeed escaped viral neutralization by the mAb, confirming the antigenic significance of the insertion. The mutant virus still replicated efficiently in vitro on primary chicken embryonic fibroblasts. When inoculated to specific pathogens-free chickens, the escape mutant, contrary to its parent virus, was not detected in the bursa and only induced a mild seroconversion in some of the inoculated birds.

This works illustrates how an avibirnavirus evolved and escaped immune pressure through polymerase stuttering. It underlines the plasticity of IBDV capsid protein that accommodated an aa insertion in its projected domain. The only other known case of such a spontaneously occurring insertion in the VP2 protein is in IBDV serotype 2, which also exhibits extensive antigenic changes and limited bursal replication, confirming the wide biological impact of these rare genetic changes.