Vaccina Virus Binding and Infection of Primary Human B Cells

Abstract

Vaccinia virus (VACV), the prototypical poxvirus, was used to eradicate smallpox worldwide and, in recent years, has received considerable attention as a vector for the development of vaccines against infectious diseases and oncolytic virus therapy. Studies have demonstrated that VACV exhibits an extremely strong bias for binding to and infection of primary human antigenpresenting cells (APCs) including monocytes, macrophages, and dendritic cells. However, very few studies have evaluated VACV binding to and infection of primary human B cells, a main type of professional APC. In this study, we evaluated the susceptibility of primary human peripheral B cells at different developmental stages to VACV binding, infection, and replication. We found that VACV exhibited strong binding but little entry into ex vivo B cells. Phenotypic analysis of B cells revealed that plasmablasts were the only subset resistant to VACV binding. Infection studies showed that plasma and mature-naïve B cells were resistant to VACV infection, while memory B cells were preferentially infected. Additionally, VACV infection was increased in larger and proliferative B cells suggesting a bias of VACV infection towards specific stages of differentiation and proliferative ability. VACV infection in B cells was abortive, and cessation of VACV infection was determined to occur at the stage of late viral gene expression. Interestingly, B cell function, measured by cytokine production, was not affected within 24 hours post-infection. In contrast to ex vivo B cells, stimulated B cells were permissive to productive VACV infection. These results demonstrate the value of B cells as a tool to aid in deciphering the intricacies of poxvirus infection in humans. Understanding VACV infection in primary human B cells at various stages of differentiation and maturation is important for the development of a safer smallpox vaccine and better vectors for vaccines against cancers and other infectious diseases.