Abstract
Despite 25 years of research, the basic virology of Kaposi Sarcoma Herpesviruses (KSHV) in B lymphocytes remains poorly understood. This study seeks to fill critical gaps in our understanding by characterizing the B lymphocyte lineage-specific tropism of KSHV. Here, we use lymphocytes derived from 40 human tonsil specimens to determine the B lymphocyte lineages targeted by KSHV early during de novo infection in our ex vivo model system. We characterize the immunological diversity of our tonsil specimens and determine that overall susceptibility of tonsil lymphocytes to KSHV infection varies substantially between donors. We demonstrate that a variety of B lymphocyte subtypes are susceptible to KSHV infection and identify CD138+ plasma cells as a highly targeted cell type for de novo KSHV infection. We determine that infection of tonsil B cell lineages is primarily latent with few lineages contributing to lytic replication. We explore the use of CD138 and heparin sulfate proteoglycans as attachment factors for the infection of B lymphocytes and conclude that they do not play a substantial role. Finally, we determine that the host T cell microenvironment influences the course of de novo infection in B lymphocytes. These results improve our understanding of KSHV transmission and the biology of early KSHV infection in a naïve human host, and lay a foundation for further characterization of KSHV molecular virology in B lymphocyte lineages.
Highlights
Kaposi Sarcoma-associated Herpesvirus (KSHV/HHV-8) is a lymphotrophic gamma-herpesvirus
Kaposi Sarcoma Herpesviruses (KSHV) infection is associated with cancer in B cells and endothelial cells, in the context of immune suppression
Our study examines KSHV infection in B cells extracted from the tonsils of 40 human donors in order to determine what types of B cells are initially targeted for infection and examine how the presence of other immune cells influence the initial stages of KSHV infection
Summary
Kaposi Sarcoma-associated Herpesvirus (KSHV/HHV-8) is a lymphotrophic gamma-herpesvirus. In addition to its role in the pathogenesis of Kaposi Sarcoma (KS) [1], KSHV infection is associated with two lymphoproliferative disorders, multicentric Castleman disease (MCD) and primary effusion lymphoma (PEL) [2,3], as well as a recently characterized inflammatory disorder KSHV inflammatory cytokine syndrome (KICS) [4]. The KSHV-associated lymphoproliferative diseases are uniformly fatal with few effective treatment options [7]. Resting peripheral B cells and many established B cell-derived cell lines are refractory to KSHV infection but unstimulated tonsil-derived lymphocytes are susceptible to infection [9]. In addition to being susceptible to ex vivo infection, tonsil lymphocytes represent a highly relevant model for understanding early infection events in KSHV transmission
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
