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Importantly, up to 30% of affected individuals develop long-term neurologic sequelae. We investigated the role of chemokine receptor Ccr5 in a mouse model of TBEV infection using the naturally attenuated tick-borne flavivirus Langat virus (LGTV). Ccr5-deficient mice presented with an increase in viral replication within the CNS and decreased survival during LGTV encephalitis compared with wild-type controls. This enhanced susceptibility was due to the temporal lag in lymphocyte migration into the CNS. Adoptive transfer of wild-type T cells, but not Ccr5-deficient T cells, significantly improved survival outcome in LGTV-infected Ccr5-deficient mice. Concomitantly, a significant increase in neutrophil migration into the CNS in LGTV-infected Ccr5\u2212\/\u2212 mice was documented at the late stage of infection. Ab-mediated depletion of neutrophils in Ccr5\u2212\/\u2212 mice resulted in a significant improvement in mortality, a decrease in viral load, and a decrease in overall tissue damage in the CNS compared with isotype control\u2013treated mice. Ccr5 is crucial in directing T cells toward the LGTV-infected brain, as well as in suppressing neutrophil-mediated inflammation within the CNS.<\/jats:p>","DOI":"10.4049\/jimmunol.1502452","type":"journal-article","created":{"date-parts":[[2016,4,30]],"date-time":"2016-04-30T03:09:30Z","timestamp":1461985770000},"page":"4622-4631","source":"Crossref","is-referenced-by-count":36,"title":["Dual Function of Ccr5 during Langat Virus Encephalitis: Reduction in Neutrophil-Mediated Central Nervous System Inflammation and Increase in T Cell\u2013Mediated Viral Clearance"],"prefix":"10.1093","volume":"196","author":[{"given":"Daniela","family":"Michlmayr","sequence":"first","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana V","family":"Bardina","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G","family":"Pletnev","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean K","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,6,1]]},"reference":[{"key":"2025030702174032400_r1","volume-title":"Tick-Borne Encephalitis Virus: A General Overview","author":"Donoso-Mantke","year":"2011"},{"key":"2025030702174032400_r2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0166-3542(02)00206-1","article-title":"Tick-borne encephalitis","volume":"57","author":"Gritsun","year":"2003","journal-title":"Antiviral Res."},{"issue":"26","key":"2025030702174032400_r3","article-title":"Tick-borne encephalitis in Europe and beyond\u2013the epidemiological situation as of 2007","volume":"13","author":"Suss","year":"2008","journal-title":"Euro Surv."},{"key":"2025030702174032400_r4","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.tmaid.2010.06.004","article-title":"Tick-borne encephalitis: pathogenesis and clinical implications","volume":"8","author":"R\u016f\u017eek","year":"2010","journal-title":"Travel Med. 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