{"id":{"repo_id":"wustl","oai_identifier":"oai:openscholarship.wustl.edu:etd-1239"},"canonical_url":"https://search.dev.ndltd.org/etd/wustl/oai:openscholarship.wustl.edu:etd-1239","repository":{"repo_id":"wustl","name":"Washington University in St. Louis","base_url":"https://openscholarship.wustl.edu/do/oai/"},"display":{"title":"The Impact Of Interferon Regulatory Factor 3 On The Immune Response To Herpes Simplex Virus Type I Infection","abstract":"The type I interferon: IFN) cascade is critical in control of herpes simplex virus type I: HSV-1) infection and relies on specific recognition molecules to rapidly signal viral infection via interferon regulatory factor-3: IRF-3) -dependent pathways. The absence of these recognition molecules or the loss of IRF-3 would be predicted to render early recognition pathways inoperative and thus impact viral infection. However, previous results had produced contradictory results in terms of the role of IRF-3 during HSV-1 infection. In this study, infected IRF-3-/- immune cells were found to support increased HSV-1 replication compared to control cells. In addition, IRF-3 deficient cells exhibited delayed type I IFN synthesis following infection and were partially restored in the presence of exogenous IFN; blockade of the type I IFN receptor resulted in similar titers in control and IRF-3-/- cells. Together, the data demonstrated that defective and deficient type I IFN production in IRF-3-/- cells resulted in increased HSV-1 replication in vitro. In vivo, IRF-3 deficiency was found to have no significant impact on HSV-1 replication in peripheral tissues following ocular challenge with a laboratory: 17) or a neurovirulent strain: McKrae) of virus. However, IRF-3-/- mice were significantly more susceptible to central nervous system infection following both peripheral and intracranial infection with HSV-1. Increased viral replication and inflammatory cytokine production were observed in brain tissues of IRF-3-/- mice compared to control mice. In addition, the production of IFNβ and IFNα was delayed and reduced in IRF-3-/- brains. These data demonstrate a critical role for IRF-3 in control of central nervous system infection following HSV-1 challenge. Together, the data illustrate the importance of IRF-3 mediated pathways in initiating the type I IFN cascade necessary to control HSV-1 infection both in vitro and in vivo.","abstract_html":"The type I interferon: IFN) cascade is critical in control of herpes simplex virus type I: HSV-1) infection and relies on specific recognition molecules to rapidly signal viral infection via interferon regulatory factor-3: IRF-3) -dependent pathways. The absence of these recognition molecules or the loss of IRF-3 would be predicted to render early recognition pathways inoperative and thus impact viral infection. However, previous results had produced contradictory results in terms of the role of IRF-3 during HSV-1 infection. In this study, infected IRF-3-/- immune cells were found to support increased HSV-1 replication compared to control cells. In addition, IRF-3 deficient cells exhibited delayed type I IFN synthesis following infection and were partially restored in the presence of exogenous IFN; blockade of the type I IFN receptor resulted in similar titers in control and IRF-3-/- cells. Together, the data demonstrated that defective and deficient type I IFN production in IRF-3-/- cells resulted in increased HSV-1 replication in vitro. In vivo, IRF-3 deficiency was found to have no significant impact on HSV-1 replication in peripheral tissues following ocular challenge with a laboratory: 17) or a neurovirulent strain: McKrae) of virus. However, IRF-3-/- mice were significantly more susceptible to central nervous system infection following both peripheral and intracranial infection with HSV-1. Increased viral replication and inflammatory cytokine production were observed in brain tissues of IRF-3-/- mice compared to control mice. In addition, the production of IFNβ and IFNα was delayed and reduced in IRF-3-/- brains. These data demonstrate a critical role for IRF-3 in control of central nervous system infection following HSV-1 challenge. Together, the data illustrate the importance of IRF-3 mediated pathways in initiating the type I IFN cascade necessary to control HSV-1 infection both in vitro and in vivo.","abstract_has_math":false,"creators":["Menachery, Vineet"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biology and Biomedical Sciences: Immunology","degree_department":null,"school":null,"contributors":["David Leib"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-01-01T08:00:00Z","date_published":"2010-01-01T08:00:00Z","updated_at":"2026-07-24T06:13:49Z","subjects":["Biology","Microbiology","Early Recognition response","HSV","IFN","IRF3","virus"],"languages":["English (en)"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7QN64R3"],"render_values":[{"text":"https://doi.org/10.7936/K7QN64R3","href":"https://doi.org/10.7936/K7QN64R3","code":true}]}]},"links":{"outbound_url":"https://openscholarship.wustl.edu/etd/240","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["David Leib"]},{"key":"dc:creator","label":"Author","values":["Menachery, Vineet"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2010-01-01T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biology and Biomedical Sciences: Immunology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology","Microbiology","Early Recognition response","HSV","IFN","IRF3","virus"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English (en)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://openscholarship.wustl.edu/etd/240"]},{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7QN64R3"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The type I interferon: IFN) cascade is critical in control of herpes simplex virus type I: HSV-1) infection and relies on specific recognition molecules to rapidly signal viral infection via interferon regulatory factor-3: IRF-3) -dependent pathways. The absence of these recognition molecules or the loss of IRF-3 would be predicted to render early recognition pathways inoperative and thus impact viral infection. However, previous results had produced contradictory results in terms of the role of IRF-3 during HSV-1 infection. In this study, infected IRF-3-/- immune cells were found to support increased HSV-1 replication compared to control cells. In addition, IRF-3 deficient cells exhibited delayed type I IFN synthesis following infection and were partially restored in the presence of exogenous IFN; blockade of the type I IFN receptor resulted in similar titers in control and IRF-3-/- cells. Together, the data demonstrated that defective and deficient type I IFN production in IRF-3-/- cells resulted in increased HSV-1 replication in vitro. In vivo, IRF-3 deficiency was found to have no significant impact on HSV-1 replication in peripheral tissues following ocular challenge with a laboratory: 17) or a neurovirulent strain: McKrae) of virus. However, IRF-3-/- mice were significantly more susceptible to central nervous system infection following both peripheral and intracranial infection with HSV-1. Increased viral replication and inflammatory cytokine production were observed in brain tissues of IRF-3-/- mice compared to control mice. In addition, the production of IFNβ and IFNα was delayed and reduced in IRF-3-/- brains. These data demonstrate a critical role for IRF-3 in control of central nervous system infection following HSV-1 challenge. Together, the data illustrate the importance of IRF-3 mediated pathways in initiating the type I IFN cascade necessary to control HSV-1 infection both in vitro and in vivo."]},{"key":"dc:title","label":"Title","values":["The Impact Of Interferon Regulatory Factor 3 On The Immune Response To Herpes Simplex Virus Type I Infection"]}]}],"canonical_facts":{"dc:contributor":["David Leib"],"dc:creator":["Menachery, Vineet"],"dc:date.available":["2010-01-01T08:00:00Z"],"dc:description.abstract":["The type I interferon: IFN) cascade is critical in control of herpes simplex virus type I: HSV-1) infection and relies on specific recognition molecules to rapidly signal viral infection via interferon regulatory factor-3: IRF-3) -dependent pathways. The absence of these recognition molecules or the loss of IRF-3 would be predicted to render early recognition pathways inoperative and thus impact viral infection. However, previous results had produced contradictory results in terms of the role of IRF-3 during HSV-1 infection. In this study, infected IRF-3-/- immune cells were found to support increased HSV-1 replication compared to control cells. In addition, IRF-3 deficient cells exhibited delayed type I IFN synthesis following infection and were partially restored in the presence of exogenous IFN; blockade of the type I IFN receptor resulted in similar titers in control and IRF-3-/- cells. Together, the data demonstrated that defective and deficient type I IFN production in IRF-3-/- cells resulted in increased HSV-1 replication in vitro. In vivo, IRF-3 deficiency was found to have no significant impact on HSV-1 replication in peripheral tissues following ocular challenge with a laboratory: 17) or a neurovirulent strain: McKrae) of virus. However, IRF-3-/- mice were significantly more susceptible to central nervous system infection following both peripheral and intracranial infection with HSV-1. Increased viral replication and inflammatory cytokine production were observed in brain tissues of IRF-3-/- mice compared to control mice. In addition, the production of IFNβ and IFNα was delayed and reduced in IRF-3-/- brains. These data demonstrate a critical role for IRF-3 in control of central nervous system infection following HSV-1 challenge. Together, the data illustrate the importance of IRF-3 mediated pathways in initiating the type I IFN cascade necessary to control HSV-1 infection both in vitro and in vivo."],"dc:identifier":["https://openscholarship.wustl.edu/etd/240"],"dc:identifier.doi":["https://doi.org/10.7936/K7QN64R3"],"dc:language":["English (en)"],"dc:subject":["Biology","Microbiology","Early Recognition response","HSV","IFN","IRF3","virus"],"dc:title":["The Impact Of Interferon Regulatory Factor 3 On The Immune Response To Herpes Simplex Virus Type I Infection"],"thesis:degree_discipline":["Biology and Biomedical Sciences: Immunology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T06:13:49Z"}