{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/163"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/163","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"Cytokine patterns in a comparative model of arenavirus infection: Implications for virulence and control of viral replication","abstract":"Guinea pig infection with the arenavirus Pichinde provides an animal model for human Lassa fever, a disease that affects 300,000 to 500,000 people a year in western Africa. Low passage Pichinde virus (P2) induces a mild disease with low viremia, while high passage Pichinde (P18) induces a severe disease with high viremia, ending in terminal shock. We hypothesized that severe disease would be associated with a suppression of potentially antiviral cytokines early in infection, and high levels of potentially pathogenic pro-inflammatory cytokines late in infection. Cytokine responses to P2 and P18 infection were measured from primary guinea pig peritoneal macrophages (PM) in vitro when measured by real time RT-PCR. In general, neither P2 nor P18 infection altered cytokine production from unstimulated PM. P18 infected PM did have lower mRNA levels of IL-1beta, IL-12p40, and MCP-1 after LPS addition when compared to P2 infected PM. During experimental guinea pig infection, P18 infection was associated with markedly increased IFN-gamma and MCP-1 mRNA levels from the initial peritoneal target cells relative to P2. P18 infected peritoneal cells had slightly decreased TNF-alpha, IL-8, and IL-12p40 transcripts relative to mock infected peritoneal cells. Late in infection, P18 infected spleens and livers had similar cytokine patterns relative to P2, but P18 infected PBL had decreased TNF-alpha, IFN-gamma, and RANTES transcripts. We also examined the ability of a decoy AP-1 thioaptamer, XBY-S2, to alter morbidity, mortality, and cytokine expression during P18 infection of guinea pigs. After two doses of XBY-S2, 50% (p=.024) of treated guinea pigs survived infection and had undetectable viremia. XBY-S2-treated P18 infected guinea pigs over time had overall increased cytokine mRNA expression of TNF-alpha, IL-8, IL-1beta, and IL-10 compared to PBS-treated P18 infected guinea pigs. A suppression of PBL IL-1beta and RANTES mRNA at day 12 of P18 infection was repeatedly observed. Conclusions from these experiments are 1) macrophage-derived cytokines do not explain the differential replication of P2 and P18 viruses, 2) high levels of IFN-gamma and MCP-1 may contribute to virulence of P18 virus, 3) over-expression of pro-inflammatory cytokines in PBL, liver, or spleen is not associated with terminal shock, 4) boosting of pro-inflammatory cytokines by an AP-1 aptamer correlates with reduced viremia and survival of P18 infection.","abstract_html":"Guinea pig infection with the arenavirus Pichinde provides an animal model for human Lassa fever, a disease that affects 300,000 to 500,000 people a year in western Africa. Low passage Pichinde virus (P2) induces a mild disease with low viremia, while high passage Pichinde (P18) induces a severe disease with high viremia, ending in terminal shock. We hypothesized that severe disease would be associated with a suppression of potentially antiviral cytokines early in infection, and high levels of potentially pathogenic pro-inflammatory cytokines late in infection. Cytokine responses to P2 and P18 infection were measured from primary guinea pig peritoneal macrophages (PM) in vitro when measured by real time RT-PCR. In general, neither P2 nor P18 infection altered cytokine production from unstimulated PM. P18 infected PM did have lower mRNA levels of IL-1beta, IL-12p40, and MCP-1 after LPS addition when compared to P2 infected PM. During experimental guinea pig infection, P18 infection was associated with markedly increased IFN-gamma and MCP-1 mRNA levels from the initial peritoneal target cells relative to P2. P18 infected peritoneal cells had slightly decreased TNF-alpha, IL-8, and IL-12p40 transcripts relative to mock infected peritoneal cells. Late in infection, P18 infected spleens and livers had similar cytokine patterns relative to P2, but P18 infected PBL had decreased TNF-alpha, IFN-gamma, and RANTES transcripts. We also examined the ability of a decoy AP-1 thioaptamer, XBY-S2, to alter morbidity, mortality, and cytokine expression during P18 infection of guinea pigs. After two doses of XBY-S2, 50% (p=.024) of treated guinea pigs survived infection and had undetectable viremia. XBY-S2-treated P18 infected guinea pigs over time had overall increased cytokine mRNA expression of TNF-alpha, IL-8, IL-1beta, and IL-10 compared to PBS-treated P18 infected guinea pigs. A suppression of PBL IL-1beta and RANTES mRNA at day 12 of P18 infection was repeatedly observed. Conclusions from these experiments are 1) macrophage-derived cytokines do not explain the differential replication of P2 and P18 viruses, 2) high levels of IFN-gamma and MCP-1 may contribute to virulence of P18 virus, 3) over-expression of pro-inflammatory cytokines in PBL, liver, or spleen is not associated with terminal shock, 4) boosting of pro-inflammatory cytokines by an AP-1 aptamer correlates with reduced viremia and survival of P18 infection.","abstract_has_math":false,"creators":["Erin P. Scott"],"institution":"The University of Texas Medical Branch","degree_name":"PhD","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Judith Aronson"],"committee_chairs":[],"committee_members":["Thomas K. Hughes","Lynn Soong","David N. McMurray","Clarence J. Peters"],"year":2005,"date_issued":"2005-07-12","date_published":"2005-07-12","updated_at":"2026-07-24T05:50:48Z","subjects":["viral hemorrhagic fever","innate immunity"],"languages":["eng"],"rights":["Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-07182005-142738"],"render_values":[{"text":"etd-07182005-142738","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2152.3/163","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Judith Aronson"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Thomas K. Hughes","Lynn Soong","David N. McMurray","Clarence J. Peters"]},{"key":"dc:creator","label":"Author","values":["Erin P. Scott"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2011-12-20T16:04:57Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2008-06-17","2011-12-20T16:04:57Z"]},{"key":"dc:date.issued","label":"Date","values":["2005-07-12"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["PhD"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["viral hemorrhagic fever","innate immunity"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-07182005-142738"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2152.3/163"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Guinea pig infection with the arenavirus Pichinde provides an animal model for human Lassa fever, a disease that affects 300,000 to 500,000 people a year in western Africa. Low passage Pichinde virus (P2) induces a mild disease with low viremia, while high passage Pichinde (P18) induces a severe disease with high viremia, ending in terminal shock. We hypothesized that severe disease would be associated with a suppression of potentially antiviral cytokines early in infection, and high levels of potentially pathogenic pro-inflammatory cytokines late in infection. Cytokine responses to P2 and P18 infection were measured from primary guinea pig peritoneal macrophages (PM) in vitro when measured by real time RT-PCR. In general, neither P2 nor P18 infection altered cytokine production from unstimulated PM. P18 infected PM did have lower mRNA levels of IL-1beta, IL-12p40, and MCP-1 after LPS addition when compared to P2 infected PM. During experimental guinea pig infection, P18 infection was associated with markedly increased IFN-gamma and MCP-1 mRNA levels from the initial peritoneal target cells relative to P2. P18 infected peritoneal cells had slightly decreased TNF-alpha, IL-8, and IL-12p40 transcripts relative to mock infected peritoneal cells. Late in infection, P18 infected spleens and livers had similar cytokine patterns relative to P2, but P18 infected PBL had decreased TNF-alpha, IFN-gamma, and RANTES transcripts. We also examined the ability of a decoy AP-1 thioaptamer, XBY-S2, to alter morbidity, mortality, and cytokine expression during P18 infection of guinea pigs. After two doses of XBY-S2, 50% (p=.024) of treated guinea pigs survived infection and had undetectable viremia. XBY-S2-treated P18 infected guinea pigs over time had overall increased cytokine mRNA expression of TNF-alpha, IL-8, IL-1beta, and IL-10 compared to PBS-treated P18 infected guinea pigs. A suppression of PBL IL-1beta and RANTES mRNA at day 12 of P18 infection was repeatedly observed. Conclusions from these experiments are 1) macrophage-derived cytokines do not explain the differential replication of P2 and P18 viruses, 2) high levels of IFN-gamma and MCP-1 may contribute to virulence of P18 virus, 3) over-expression of pro-inflammatory cytokines in PBL, liver, or spleen is not associated with terminal shock, 4) boosting of pro-inflammatory cytokines by an AP-1 aptamer correlates with reduced viremia and survival of P18 infection."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["electronic"]},{"key":"dc:title","label":"Title","values":["Cytokine patterns in a comparative model of arenavirus infection: Implications for virulence and control of viral replication"]}]}],"canonical_facts":{"dc:contributor.advisor":["Judith Aronson"],"dc:contributor.committeemember":["Thomas K. Hughes","Lynn Soong","David N. McMurray","Clarence J. Peters"],"dc:creator":["Erin P. Scott"],"dc:date.accessioned":["2011-12-20T16:04:57Z"],"dc:date.available":["2008-06-17","2011-12-20T16:04:57Z"],"dc:date.issued":["2005-07-12"],"dc:description.abstract":["Guinea pig infection with the arenavirus Pichinde provides an animal model for human Lassa fever, a disease that affects 300,000 to 500,000 people a year in western Africa. Low passage Pichinde virus (P2) induces a mild disease with low viremia, while high passage Pichinde (P18) induces a severe disease with high viremia, ending in terminal shock. We hypothesized that severe disease would be associated with a suppression of potentially antiviral cytokines early in infection, and high levels of potentially pathogenic pro-inflammatory cytokines late in infection. Cytokine responses to P2 and P18 infection were measured from primary guinea pig peritoneal macrophages (PM) in vitro when measured by real time RT-PCR. In general, neither P2 nor P18 infection altered cytokine production from unstimulated PM. P18 infected PM did have lower mRNA levels of IL-1beta, IL-12p40, and MCP-1 after LPS addition when compared to P2 infected PM. During experimental guinea pig infection, P18 infection was associated with markedly increased IFN-gamma and MCP-1 mRNA levels from the initial peritoneal target cells relative to P2. P18 infected peritoneal cells had slightly decreased TNF-alpha, IL-8, and IL-12p40 transcripts relative to mock infected peritoneal cells. Late in infection, P18 infected spleens and livers had similar cytokine patterns relative to P2, but P18 infected PBL had decreased TNF-alpha, IFN-gamma, and RANTES transcripts. We also examined the ability of a decoy AP-1 thioaptamer, XBY-S2, to alter morbidity, mortality, and cytokine expression during P18 infection of guinea pigs. After two doses of XBY-S2, 50% (p=.024) of treated guinea pigs survived infection and had undetectable viremia. XBY-S2-treated P18 infected guinea pigs over time had overall increased cytokine mRNA expression of TNF-alpha, IL-8, IL-1beta, and IL-10 compared to PBS-treated P18 infected guinea pigs. A suppression of PBL IL-1beta and RANTES mRNA at day 12 of P18 infection was repeatedly observed. Conclusions from these experiments are 1) macrophage-derived cytokines do not explain the differential replication of P2 and P18 viruses, 2) high levels of IFN-gamma and MCP-1 may contribute to virulence of P18 virus, 3) over-expression of pro-inflammatory cytokines in PBL, liver, or spleen is not associated with terminal shock, 4) boosting of pro-inflammatory cytokines by an AP-1 aptamer correlates with reduced viremia and survival of P18 infection."],"dc:format.medium":["electronic"],"dc:identifier.other":["etd-07182005-142738"],"dc:identifier.uri":["http://hdl.handle.net/2152.3/163"],"dc:language.iso":["eng"],"dc:rights":["Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works."],"dc:subject":["viral hemorrhagic fever","innate immunity"],"dc:title":["Cytokine patterns in a comparative model of arenavirus infection: Implications for virulence and control of viral replication"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["PhD"],"thesis:institution_name":["The University of Texas Medical Branch"]},"updated_at":"2026-07-24T05:50:48Z"}