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

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 4...

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Bibliographic Details
Published in:PLoS pathogens 2020-10, Vol.16 (10), p.e1008968-e1008968
Main Authors: Aalam, Farizeh, Nabiee, Romina, Castano, Jesus Ramirez, Totonchy, Jennifer
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
Adolescent
Adult
Age
Aged
AIDS
B-Lymphocytes - immunology
B-Lymphocytes - virology
Biology and Life Sciences
Care and treatment
Cell Lineage
Cellular proteins
Child
Child, Preschool
Development and progression
Female
Flow cytometry
Genetic aspects
Health aspects
Heparin
Herpesvirus 8, Human - immunology
HIV
Host-virus relationships
Human immunodeficiency virus
Humans
Immune response
Immunology
Infections
Kaposi's sarcoma
Kaposis sarcoma
Lymphocytes
Lymphocytes B
Lymphocytes T
Male
Medicine and Health Sciences
Middle Aged
Palatine Tonsil - immunology
Palatine Tonsil - virology
Pharmacy
Plasma
Plasma cells
Plasma Cells - immunology
Plasma Cells - virology
Proteoglycans
Research and Analysis Methods
Sarcoma
Sarcoma, Kaposi - immunology
Sarcoma, Kaposi - virology
Syndecan-1 - metabolism
Tonsil
Tropism
Virus Latency
Young Adult
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1008968