{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:30:38Z","timestamp":1790267438342,"version":"4.1.0"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Upon activation of Toll-like and RIG-I-like receptor signaling pathways, the transcription factor IRF5 translocates to the nucleus and induces antiviral immune programs. The recent discovery of a homozygous mutation in the immunoregulatory gene guanine exchange factor dedicator of cytokinesis 2 (\n                    <jats:italic>Dock2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>mu\/mu<\/jats:italic>\n                    <\/jats:sup>\n                    ) in several\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mouse colonies has complicated interpretation of immune functions previously ascribed to IRF5. To define the antiviral functions of IRF5\n                    <jats:italic>in vivo<\/jats:italic>\n                    , we infected backcrossed\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    \u00d7\n                    <jats:italic>Dock2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>wt\/wt<\/jats:italic>\n                    <\/jats:sup>\n                    mice (here called\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice) and independently generated CMV-Cre\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    mice with West Nile virus (WNV), a pathogenic neurotropic flavivirus. Compared to congenic wild-type animals,\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and CMV-Cre\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    mice were more vulnerable to WNV infection, and this phenotype was associated with increased infection in peripheral organs, which resulted in higher virus titers in the central nervous system. The loss of IRF5, however, was associated with only small differences in the type I interferon response systemically and in the draining lymph node during WNV infection. Instead, lower levels of several other proinflammatory cytokines and chemokines, as well as fewer and less activated immune cells, were detected in the draining lymph node 2 days after WNV infection. WNV-specific antibody responses in\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice also were blunted in the context of live or inactivated virus infection and this was associated with fewer antigen-specific memory B cells and long-lived plasma cells. Our results with\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice establish a key role for IRF5 in shaping the early innate immune response in the draining lymph node, which impacts the spread of virus infection, optimal B cell immunity, and disease pathogenesis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    Although the roles of IRF3 and IRF7 in orchestrating innate and adaptive immunity after viral infection are established, the function of the related transcription factor IRF5 remains less certain. Prior studies in\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice reported conflicting results as to the contribution of IRF5 in regulating type I interferon and adaptive immune responses. The lack of clarity may stem from a recently discovered homozygous loss-of-function mutation of the immunoregulatory gene\n                    <jats:italic>Dock2<\/jats:italic>\n                    in several colonies of\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Here, using a mouse model with a deficiency in IRF5 and wild-type Dock2 alleles, we investigated how IRF5 modulates West Nile virus (WNV) pathogenesis and host immune responses. Our\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies indicate that IRF5 has a key role in shaping the early proinflammatory cytokine response in the draining lymph node, which impacts immunity and control of WNV infection.\n                  <\/jats:p>","DOI":"10.1128\/jvi.01545-14","type":"journal-article","created":{"date-parts":[[2014,7,17]],"date-time":"2014-07-17T00:37:36Z","timestamp":1405557456000},"page":"11007-11021","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Interferon Regulatory Factor 5-Dependent Immune Responses in the Draining Lymph Node Protect against West Nile Virus Infection"],"prefix":"10.1128","volume":"88","author":[{"given":"Larissa B.","family":"Thackray","sequence":"first","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bimmi","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin M.","family":"Richner","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Miner","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia K.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, 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Genetic variants and disease-associated factors contribute to enhanced interferon regulatory factor 5 expression in blood cells of patients with systemic lupus erythematosus. 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