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To address the importance of DC activation for RABV vaccine efficacy, the genes for several DC recruitment and\/or activation molecules, e.g., granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage-derived chemokine (MDC), and macrophage inflammatory protein 1\u03b1 (MIP-1\u03b1), were individually cloned into RABV. The ability of these recombinant viruses to activate DCs was determined<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. Infection of mouse bone marrow-derived DCs with each of the recombinant viruses resulted in DC activation, as shown by increased surface expression of CD11c and CD86 as well as an increased level of alpha interferon (IFN-\u03b1) production compared to levels observed after infection with the parent virus. Intramuscular infection of mice with each of the viruses recruited and\/or activated more DCs and B cells in the periphery than infection with the parent virus, leading to the production of higher levels of virus-neutralizing antibodies. Furthermore, a single immunization with recombinant RABV expressing GM-CSF or MDC protected significantly more mice against intracerebral challenge with virulent RABV than did immunization with the parental virus. Yet, these viruses did not show more virulence than the parent virus, since direct intracerebral inoculation with each virus at up to 1 \u00d7 10<jats:sup>7<\/jats:sup>fluorescent focus units each did not induce any overt clinic symptom, such as abnormal behavior, or any neurological signs. Together, these data indicate that recombinant RABVs expressing these molecules activate\/recruit DCs and enhance protective immune responses.<\/jats:p>","DOI":"10.1128\/jvi.01552-10","type":"journal-article","created":{"date-parts":[[2010,11,25]],"date-time":"2010-11-25T03:51:05Z","timestamp":1290657065000},"page":"1634-1644","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":93,"title":["Rabies Virus Expressing Dendritic Cell-Activating Molecules Enhances the Innate and Adaptive Immune Response to Vaccination"],"prefix":"10.1128","volume":"85","author":[{"given":"Yongjun","family":"Wen","sequence":"first","affiliation":[{"name":"Departments of Pathology, University of Georgia, Athens, Georgia 30602"},{"name":"Institute of Special Economic Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Zuojia, Jilin 132109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualei","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Pathology, University of Georgia, Athens, Georgia 30602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Special Economic Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Zuojia, Jilin 132109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuhe","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Special Economic Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Zuojia, Jilin 132109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph A.","family":"Tripp","sequence":"additional","affiliation":[{"name":"Infectious Diseases, University of Georgia, Athens, Georgia 30602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Infectious Diseases, University of Georgia, Athens, Georgia 30602"},{"name":"Anatomy and Radiology, University of Georgia, Athens, Georgia 30602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen F.","family":"Fu","sequence":"additional","affiliation":[{"name":"Departments of Pathology, University of Georgia, Athens, Georgia 30602"},{"name":"Infectious Diseases, University of Georgia, Athens, Georgia 30602"},{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.767"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/32588"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023427228024"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.7.4043"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0086"},{"key":"e_1_3_2_7_2","first-page":"195","volume":"20","year":"1989","unstructured":"Blancou, J., et al. 1989. 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