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To evaluate the effect of overexpression of chemokines on RABV infection, chemokines macrophage inflammatory protein 1\u03b1 (MIP-1\u03b1), RANTES, and IP-10 were individually cloned into the genome of attenuated RABV strain HEP-Flury. These recombinant RABVs were characterized in vitro for growth properties and expression of chemokines. It was found that all the recombinant viruses grew as well as the parent virus, and each of the viruses expressed the intended chemokine in a dose-dependent manner. When these viruses were evaluated for pathogenicity in the mouse model, it was found that overexpression of MIP-1\u03b1 further decreased RABV pathogenicity by inducing a transient innate immune response. In contrast, overexpression of RANTES or IP-10 increased RABV pathogenicity by causing neurological diseases, which is due to persistent and high-level expression of chemokines, excessive infiltration and accumulation of inflammatory cells in the central nervous system, and severe enhancement of blood-brain barrier permeability. These studies indicate that overexpression of chemokines, although important in controlling virus infection, may not always be beneficial to the host.<\/jats:p>","DOI":"10.1128\/jvi.01346-09","type":"journal-article","created":{"date-parts":[[2009,9,10]],"date-time":"2009-09-10T00:45:40Z","timestamp":1252543540000},"page":"11808-11818","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":78,"title":["The Roles of Chemokines in Rabies Virus Infection: Overexpression May Not Always Be Beneficial"],"prefix":"10.1128","volume":"83","author":[{"given":"Ling","family":"Zhao","sequence":"first","affiliation":[{"name":"Departments of Pathology"},{"name":"State-Key Laboratory of Agricultural Microbiology, Department of Preventive Veterinary, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harufusa","family":"Toriumi","sequence":"additional","affiliation":[{"name":"Departments of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Kuang","sequence":"additional","affiliation":[{"name":"Departments of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanchun","family":"Chen","sequence":"additional","affiliation":[{"name":"State-Key Laboratory of Agricultural Microbiology, Department of Preventive Veterinary, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen F.","family":"Fu","sequence":"additional","affiliation":[{"name":"Departments of Pathology"},{"name":"Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602"},{"name":"State-Key Laboratory of Agricultural Microbiology, Department of Preventive Veterinary, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"279","volume":"5","year":"1964","unstructured":"Abelseth, M. 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