African swine fever virus: a B cell-mitogenic virus in vivo and in vitro

The two major characteristics of pathogenesis in African swine fever virus (ASFV) infections of domestic pigs are massive B-cell apoptosis and haemorr hage. The effects of ASFV on porcine B cells have therefore been systematic ally examined in vivo, by using virus-infected pigs and SCID-Beige mice rec onstituted with porcine bone marrow, and in vitro, by using porcine B-cell lines and B cells from normal and ASFV-infected pigs, Secretion of porcine Ig was stimulated by ASFV both in vivo and in bone marrow cultures in vitro , with the virulent Malawi isolate of ASFV being the most effective. Stimul ation of Ig secretion in vitro depended on the presence of ASFV-infected ma crophages and did not occur with supernatants from ASFV-infected macrophage s. Although the virus alone did not stimulate proliferation of purified B c ells in vitro, it was co-stimulatory with CD154 (CD40 ligand), The B cells recovered from ASFV-infected porcine lymphoid tissue were of activated surf ace marker phenotypes and, interestingly, expressed diminished levels of th e B-cell co-stimulatory surface molecule CD21, In addition, they were highl y sensitive to IL-4 and CD154, These results may be integrated into a model of pathogenesis in which those B cells activated indirectly as a result of virulent ASFV infection of macrophages are not rescued from apoptosis thro ugh interaction with CD154, due to the drastic depletion of T cells that oc curs early in infection, The consequently diminished specific anti-ASFV ant ibody response would favour survival of the virus, with the non-specific hy pergammaglobulinaemia being perhaps another example of pathogen-mediated im mune deviation.