{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10453"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10453","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Impaired Control of Chronic Herpesvirus Infection in Tissue Resident Macrophages During Coinfection with Intestinal Parasite and Other Cell-intrinsic Herpesvirus Interactions","abstract":"Gammaherpesviruses are chronic pathogens that infect lymphocytes, such as B cells, dendritic cells, and macrophages. Reactivation of gammaherpesviruses is thought to induce lymphomas and can be caused by a variety of signals, such as HDAC inhibitors. While some of these signals are known, it is still unclear whether there are cell-specific reactivation mechanisms, and if so, which signals cause them. Further, human gammaherpesviruses are endemic in areas that also have a high prevalence of helminth infections. Coinfection with parasites has been shown to induce murine gammaherpesvirus-68 (MHV68) reactivation in vivo, suggesting that coinfection with chronic pathogens is one mechanism herpesviruses can use to reactivate. To examine cell-specific MHV68 reactivation, we utilized conditional knockout mice to remove IL-4 receptor signaling on B cells or macrophages. We found that IL-4 signaling in combination with interferon-γ blockade reactivates MHV68 from latently infected macrophages, but not B cells. We continued our work on cell-specific reactivation signals by examining MHV68 infection in tissue resident peritoneal macrophages, called large peritoneal macrophages (LPMs), during coinfection with a parasite, Heligmosomoides polygyrus (HP). We found that coinfection with HP increases the number of MHV68-infected LPMs during acute replication and latency. Further, coinfected mice had increased ex vivo reactivation of MHV68. By using dietary and genetic depletion of the LPMs, we found that HP-induced expansion of the LPMs was necessary for the increased infection and reactivation. Overall, this work demonstrates a new role for LPMs during viral infection and highlights cell-specific mechanisms gammaherpesviruses use to reactivate from latency.","abstract_html":"Gammaherpesviruses are chronic pathogens that infect lymphocytes, such as B cells, dendritic cells, and macrophages. Reactivation of gammaherpesviruses is thought to induce lymphomas and can be caused by a variety of signals, such as HDAC inhibitors. While some of these signals are known, it is still unclear whether there are cell-specific reactivation mechanisms, and if so, which signals cause them. Further, human gammaherpesviruses are endemic in areas that also have a high prevalence of helminth infections. Coinfection with parasites has been shown to induce murine gammaherpesvirus-68 (MHV68) reactivation in vivo, suggesting that coinfection with chronic pathogens is one mechanism herpesviruses can use to reactivate. To examine cell-specific MHV68 reactivation, we utilized conditional knockout mice to remove IL-4 receptor signaling on B cells or macrophages. We found that IL-4 signaling in combination with interferon-γ blockade reactivates MHV68 from latently infected macrophages, but not B cells. We continued our work on cell-specific reactivation signals by examining MHV68 infection in tissue resident peritoneal macrophages, called large peritoneal macrophages (LPMs), during coinfection with a parasite, Heligmosomoides polygyrus (HP). We found that coinfection with HP increases the number of MHV68-infected LPMs during acute replication and latency. Further, coinfected mice had increased ex vivo reactivation of MHV68. By using dietary and genetic depletion of the LPMs, we found that HP-induced expansion of the LPMs was necessary for the increased infection and reactivation. Overall, this work demonstrates a new role for LPMs during viral infection and highlights cell-specific mechanisms gammaherpesviruses use to reactivate from latency.","abstract_has_math":false,"creators":["Zarek, Christina Marie"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Yan, Nan","Hooper, Lora V.","Pfeiffer, Julie K.","Reese, Tiffany A."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-01-02T21:58:05Z","date_published":"2025-01-02T21:58:05Z","updated_at":"2026-07-24T05:52:15Z","subjects":["Coinfection","Gammaherpesvirinae","Herpesviridae Infections","Latent Infection","Macrophage Activation","Parasitic Diseases"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1482732372"],"render_values":[{"text":"1482732372","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10453","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Yan, Nan","Hooper, Lora V.","Pfeiffer, Julie K.","Reese, Tiffany A."]},{"key":"dc:creator","label":"Author","values":["Zarek, Christina Marie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-01-02T21:58:05Z","2022-12","December 2022","2025-01-02T21:58:06Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Coinfection","Gammaherpesvirinae","Herpesviridae Infections","Latent Infection","Macrophage Activation","Parasitic Diseases"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/10453","1482732372"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Gammaherpesviruses are chronic pathogens that infect lymphocytes, such as B cells, dendritic cells, and macrophages. Reactivation of gammaherpesviruses is thought to induce lymphomas and can be caused by a variety of signals, such as HDAC inhibitors. While some of these signals are known, it is still unclear whether there are cell-specific reactivation mechanisms, and if so, which signals cause them. Further, human gammaherpesviruses are endemic in areas that also have a high prevalence of helminth infections. Coinfection with parasites has been shown to induce murine gammaherpesvirus-68 (MHV68) reactivation in vivo, suggesting that coinfection with chronic pathogens is one mechanism herpesviruses can use to reactivate. To examine cell-specific MHV68 reactivation, we utilized conditional knockout mice to remove IL-4 receptor signaling on B cells or macrophages. We found that IL-4 signaling in combination with interferon-γ blockade reactivates MHV68 from latently infected macrophages, but not B cells. We continued our work on cell-specific reactivation signals by examining MHV68 infection in tissue resident peritoneal macrophages, called large peritoneal macrophages (LPMs), during coinfection with a parasite, Heligmosomoides polygyrus (HP). We found that coinfection with HP increases the number of MHV68-infected LPMs during acute replication and latency. Further, coinfected mice had increased ex vivo reactivation of MHV68. By using dietary and genetic depletion of the LPMs, we found that HP-induced expansion of the LPMs was necessary for the increased infection and reactivation. Overall, this work demonstrates a new role for LPMs during viral infection and highlights cell-specific mechanisms gammaherpesviruses use to reactivate from latency."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Impaired Control of Chronic Herpesvirus Infection in Tissue Resident Macrophages During Coinfection with Intestinal Parasite and Other Cell-intrinsic Herpesvirus Interactions"]}]}],"canonical_facts":{"dc:contributor":["Yan, Nan","Hooper, Lora V.","Pfeiffer, Julie K.","Reese, Tiffany A."],"dc:creator":["Zarek, Christina Marie"],"dc:date":["2025-01-02T21:58:05Z","2022-12","December 2022","2025-01-02T21:58:06Z"],"dc:description":["Gammaherpesviruses are chronic pathogens that infect lymphocytes, such as B cells, dendritic cells, and macrophages. Reactivation of gammaherpesviruses is thought to induce lymphomas and can be caused by a variety of signals, such as HDAC inhibitors. While some of these signals are known, it is still unclear whether there are cell-specific reactivation mechanisms, and if so, which signals cause them. Further, human gammaherpesviruses are endemic in areas that also have a high prevalence of helminth infections. Coinfection with parasites has been shown to induce murine gammaherpesvirus-68 (MHV68) reactivation in vivo, suggesting that coinfection with chronic pathogens is one mechanism herpesviruses can use to reactivate. To examine cell-specific MHV68 reactivation, we utilized conditional knockout mice to remove IL-4 receptor signaling on B cells or macrophages. We found that IL-4 signaling in combination with interferon-γ blockade reactivates MHV68 from latently infected macrophages, but not B cells. We continued our work on cell-specific reactivation signals by examining MHV68 infection in tissue resident peritoneal macrophages, called large peritoneal macrophages (LPMs), during coinfection with a parasite, Heligmosomoides polygyrus (HP). We found that coinfection with HP increases the number of MHV68-infected LPMs during acute replication and latency. Further, coinfected mice had increased ex vivo reactivation of MHV68. By using dietary and genetic depletion of the LPMs, we found that HP-induced expansion of the LPMs was necessary for the increased infection and reactivation. Overall, this work demonstrates a new role for LPMs during viral infection and highlights cell-specific mechanisms gammaherpesviruses use to reactivate from latency."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/10453","1482732372"],"dc:language":["en"],"dc:subject":["Coinfection","Gammaherpesvirinae","Herpesviridae Infections","Latent Infection","Macrophage Activation","Parasitic Diseases"],"dc:title":["Impaired Control of Chronic Herpesvirus Infection in Tissue Resident Macrophages During Coinfection with Intestinal Parasite and Other Cell-intrinsic Herpesvirus Interactions"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:15Z"}