Vaccinia virus preferentially infects primary human memory B cells

Abstract

Abstract Vaccinia virus (VACV) has shown an extreme preference for binding to and infection of primary human antigen-presenting cells including monocytes, macrophages, and dendritic cells in the peripheral blood. Although VACV infection in monocytes, macrophages, and dendritic cells has been examined, few studies have evaluated VACV infection in B cells. In this study, we characterized VACV binding to and infection of primary human B cells. Flow cytometric analysis revealed that B cells isolated from human peripheral blood mononuclear cells exhibited two distinct populations of B cells, referred to as Bsmall and Blarge. Phenotypic analysis demonstrated that the Bsmall compartment was more quiescent compared to the Blarge population and enriched with CD138-positive plasma cells. VACV preferentially entered into and infected memory B cells. Especially, VACV preferentially infected ex vivo CXCR5+ B cells, particularly CXCR5+HLA-DRhigh B cells. Assessment of VACV gene expression by RT-PCR in total B cells to evaluate permissiveness of VACV infection in B cells revealed early and intermediate viral gene expression, but little to no late viral gene expression, suggesting that VACV infection was aborted at the late viral gene expression stage in unstimulated B cells. Additionally, preliminary data demonstrated enhanced VACV binding to and infection of B cells stimulated by B cell receptor crosslinking and TLR-9 agonist treatment. With the risk of smallpox or monkeypox being used as bioterrorism agents and the multitude of adverse reactions to the current vaccine, understanding VACV infection in B cells is important for developing a better smallpox vaccine.