Indiana University-Purdue University Indianapolis (IUPUI) / 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.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/18091 |
| Date | 12 1900 |
| Creators | Shepherd, Nicole Elizabeth |
| Contributors | Yu, Andy Qigui, Androphy, Elliot J., Blum, Janice S., Serezani, Henrique |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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