Dataset Information

Analysis of KSHV B lymphocyte lineage tropism in human tonsil reveals efficient infection of CD138+ plasma cells.

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.

SUBMITTER: Aalam F

PROVIDER: S-EPMC7595638 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Analysis of KSHV B lymphocyte lineage tropism in human tonsil reveals efficient infection of CD138+ plasma cells.

Aalam Farizeh F Nabiee Romina R Castano Jesus Ramirez JR Totonchy Jennifer J

PLoS pathogens 20201019 10

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 s ...[more]

PMID: 33075105

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Project description:Emerging data demonstrated that the gut microbiota plays an important role in protecting the integrity of the epithelial barrier, forming a mucosal immune system, and maintaining intestinal homeostasis through its metabolites. However, the intestinal microbiota community can be affected by environmental factors, such as litter, photoperiod, or temperature. Thus, we investigated the effect of different monochromatic light combinations on cecal microbiota composition as well as explored the molecular mechanism by how the external light color information mediate cecal tonsil T lymphocyte proliferation. In this study, a total of 160 chicks were exposed to monochromatic light [red (R), green (G), blue (B), or white (W) light] or green and blue monochromatic light combination (G→B) from P0 to P42. The 16S rRNA microbial sequencing results showed that the richness and diversity of the cecum microbiota and the abundance of Faecalibacterium and Butyricicoccus were significantly increased in the G→B. With consistency in the upregulation of antioxidant enzyme ability and downregulation of pro-inflammation levels in the cecum, we observed an increase in the number of goblet cells, secretory IgA+ cells, tight junction protein (occludin, ZO-1, and claudin-1) and MUC-2 expression in the cecum of the G→B. The metabolomics analysis revealed that the relative abundance of metabolites related to butyrate was significantly increased in G→B. In an in vitro experiment, we found that butyrate could effectively induce T lymphocyte proliferation and cyclin D1 protein expression. However, these butyrate responses were abrogated by HDAC3 agonists, STAT3 antagonists, or mTOR antagonists but were mimicked by GPR43 agonists or HDAC3 antagonists. Thus, we suggested that G→B can indirectly affect the composition of cecal microbiota as well as increase the relative abundance of Faecalibacterium and Butyricicoccus and butyrate production by reducing the level of oxidative stress in the cecum. Exogenous butyrate could promote the T lymphocyte proliferation of cecal tonsil by activating the GPR43/HDAC3/p-STAT3/mTOR pathways.

Dataset Information

Analysis of KSHV B lymphocyte lineage tropism in human tonsil reveals efficient infection of CD138+ plasma cells.

Publications

Analysis of KSHV B lymphocyte lineage tropism in human tonsil reveals efficient infection of CD138+ plasma cells.

Similar Datasets

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