Defining the role of plasma cells in the establishment of KSHV infection in human tonsil
Document text
Principal Investigator: Jennifer E Totonchy Organization: CHAPMAN UNIVERSITY Fiscal Year: 2024 Award: $104,855 Funding agency: National Cancer Institute Abstract/Project Summary Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic human herpesvirus, which causes Kaposi sarcoma (KS) as well as B cell lymphoproliferative disorders in the absence of adequate immune control. KSHV- associated tumors are a significant cause of morbidity and mortality in transplant patients and individuals with HIV- disease. The oral cavity is an important site for KSHV biology because saliva is believed to be the primary mode of person-to-person transmission for the virus. The tonsil and other oral lymphoid tissues represent a logical anatomical site for early infection events because they are in contact with saliva and are rich in target cell types for KSHV infection including endothelial cells and B lymphocytes. Despite this, the biology of KSHV in the human tonsil remains poorly understood. We have developed an extensive library of human tonsil specimens and a robust ex vivo infection model KSHV in tonsil-derived lymphocytes. Using these tools, we have recently discovered that mature plasma cells are highly targeted early in KSHV infection and that KSHV-infected plasma cells display a mixture of latent and lytic infection cycles. The current proposal will test several hypotheses: (1) plasma cell infection serves as an amplification step which is important for the overall establishment of infection in tonsil lymphocytes, (2) the KSHV-encoded cytokine vIL-6 is critical for establishment of KSHV infection in lymphocytes via manipulation of plasma cell biology and (3) the T cell-derived cellular cytokine IL-21 supports KSHV dissemination by driving differentiation of plasma cells, and can partially replace the function of vIL-6 in early infection. The results of this research will provide critical mechanistic details that will enhance our understanding of early events in KSHV transmission and the establishment of KSHV infection in the lymphocyte compartment. Terms: <AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Anatomic Sites><Anatomic structures><Anatomy><Antibodies><Automobile Driving><B blood cells><B cell><B cells><B-Cell Subsets><B-Cells><B-Lymphocyte Subsets><B-Lymphocytes><B-cell><Biologic Models><Biological Models><Biology><Blood Plasma Cell><Body Tissues><Buccal Cavity><Buccal Cavity Head and Neck><Cancers><Causality><Cavitas Oris><Cell Body><Cell Communication and Signaling><Cell Count><Cell Lineage><Cell Number><Cell Signaling><Cells><Cellular biology><Disease><Disorder><Endothelial Cells><Epithelial Cells><Etiology><Event><Exposure to><Gene Transcription><Genetic Transcription><Goals><HHV-8><HHV8><HIV><Herpes infection><Herpesviridae><Herpesviridae Infections><Herpesviridae disease><Herpesvirus Infections><Herpesviruses><Human><Human Herpesvirus 8><Human Immunodeficiency Viruses><IL21><Immune><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune system><Immunes><Immunochemical Immunologic><Immunodeficiency and Immunosuppression Disorders><Immunologic><Immunologic Diseases><Immunological><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Immunologically><Immunologics><Individual><Infection><Infectious Agent><Inflammatory><Intracellular Communication and Signaling><Invaded><KSHV><Kaposi Sarcoma><Kaposi Sarcoma-Associated Herpes Virus><Kaposi Sarcoma-Associated Herpesvirus><Kaposi sarcoma associated virus><Kaposi sarcoma herpes virus><Kaposi's Sarcoma><Kaposi's sarcoma (KS)-associated herpesvirus><LAV-HTLV-III><Libraries><Link><Lymphadenopathy-Associated Virus><Lymphatic Endothelial Cells><Lymphatic Tissue><Lymphatic cell><Lymphocyte><Lymphocytic><Lymphoid Tissue><Lymphoproliferative Disorders><Lytic><Lytic Cycle><Lytic Infection><Lytic Phase><Maintenance><Malignant Neoplasms><Malignant Tumor><Mesenchymal><Model System><Modeling><Modern Man><Morbidity><Morbidity - disease rate><Mouth><Mucosa><Mucosal Tissue><Mucous Membrane><Multicentric Angiofollicular Lymphoid Hyperplasia><Multicentric Castleman's Disease><Multiple Hemorrhagic Sarcoma><Oncogenic><Oral><Oral cavity><Persons><Plasma Cells><Plasmacytes><Play><RNA Expression><Recombinant Proteins><Research><Research Specimen><Role><Saliva><Signal Transduction><Signal Transduction Systems><Signaling><Site><Specimen><Syndrome><T-Cell Subsets><T-Cells><T-Lymphocyte><T-Lymphocyte Subsets><Testing><Tissues><Tonsil><Transcription><Transmission><Transplant Recipients><Tropism><Viral><Viral Diseases><Virus><Virus Diseases><Virus-HHV8><Virus-HIV><Work><biological signal transduction><causation><cell biology><cell type><cytokine><design><designing><disease causation><driving><herpes virus><infectious organism><insight><interleukin-21><kaposi's sarcoma herpesvirus><kaposi's sarcoma-associated human herpesvirus><latent infection><lymph cell><lymphoproliferative disease><malignancy><mortality><multicastleman's diseases><mutant><neoplasm/cancer><novel><oral immunology><plasma cell differentiation><plasmocyte><primary effusion lymphoma><programs><social role><thymus derived lymphocyte><tonsillar><tool><transmission process><transplant patient><tumor><viral infection><viral transmission><virus infection><virus transmission><virus-induced disease>