{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:02:07Z","timestamp":1783702927817,"version":"3.55.0"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"24","license":[{"start":{"date-parts":[[2011,12,15]],"date-time":"2011-12-15T00:00:00Z","timestamp":1323907200000},"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":[[2011,12,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), and \u0394vhs, an avirulent recombinant lacking the virion host shutoff (vhs) function. In addition, two mouse strains were used: strain 129 (control) and a Stat1-deficient (Stat1\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ) strain. Using combinations of these virus and mouse strains, we established a model of infection resulting in three different outcomes: viral clearance without neurological disease (\u0394vhs infection of control mice), neurological disease followed by viral clearance (\u0394vhs infection of Stat1\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice and WT infection of control mice), or neurological disease followed by death (WT infection of Stat1\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice). Through the use of functional genomics on the infected brain stems, we determined gene signatures that were representative of the three infection outcomes. We demonstrated a pathological signature in the brain stem of Stat1-deficient mice characterized by upregulation of transcripts encoding chemokine receptors, inflammatory markers, neutrophil chemoattractants, leukocyte adhesion proteins, and matrix metalloproteases. Additionally, there was a greater than 100-fold increase in the inflammatory markers interleukin 1\u03b2 (IL-1\u03b2) and IL-6. Consistent with this gene signature, we demonstrated profound CNS inflammation with a concomitant lethal breach of the BBB. Taken together, our results indicated an essential role for normal Stat1-dependent signaling in mediating a nonpathological immune response to viral CNS infection.\n          <\/jats:p>","DOI":"10.1128\/jvi.06032-11","type":"journal-article","created":{"date-parts":[[2011,10,13]],"date-time":"2011-10-13T02:31:46Z","timestamp":1318473106000},"page":"12972-12981","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Functional Genomics Reveals an Essential and Specific Role for Stat1 in Protection of the Central Nervous System following Herpes Simplex Virus Corneal Infection"],"prefix":"10.1128","volume":"85","author":[{"given":"Tracy Jo","family":"Pasieka","sequence":"first","affiliation":[{"name":"Departments of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Cilloniz","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Washington School of Medicine, Seattle, Washington"},{"name":"Washington National Primate Research Center, Seattle, Washington 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria S.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Washington School of Medicine, Seattle, Washington"},{"name":"Washington National Primate Research Center, Seattle, Washington 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Rosato","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, New Hampshire 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Katze","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Washington School of Medicine, Seattle, Washington"},{"name":"Washington National Primate Research Center, Seattle, Washington 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Leib","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, New Hampshire 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