Unraveling the role of B cells in the pathogenesis of an oncogenic avian herpesvirus

Significance Marek’s disease virus (MDV) infects chickens and causes the most frequent clinically diagnosed cancer in the animal kingdom, and it is used as a small-animal model for virus-induced tumor formation. Until now, B cells were thought to play a central role in MDV pathogenesis. We disproved this dogma using knockout (KO) chickens that lack mature and peripheral B cells. We demonstrated that B cells are dispensable for virus replication, virus spread, and tumor formation. In the absence of B cells, T cells facilitate efficient virus replication and are subsequently transformed, resulting in deadly lymphomas. Our data pioneer the use of KO chickens in infectious disease research and expand the knowledge on the life cycle of this highly oncogenic virus.