caa a22 4500 605501165 CHVBK 20210128100559.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00253-015-6819-3 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6819-3 Replacement of pr gene with Japanese encephalitis virus pr using reverse genetics reduces antibody-dependent enhancement of dengue virus 2 infection [Elektronische Daten] [Ying Wang, Lulu Si, Yayan Luo, Xiaolan Guo, Junmei Zhou, Danyun Fang, Huijun Yan, Gucheng Zeng, Lifang Jiang] Severe dengue is more likely found during secondary heterologous dengue virus (DENV) infection or primary infection of infants born to dengue-immune mothers and led to the hypothesis of antibody-dependent enhancement (ADE). It has been reported that pre-membrane (prM)-reactive antibodies do not efficiently neutralize DENV infection but instead potently promote ADE infection. Meanwhile, these enhancing anti-prM antibodies mainly react with the precursor (pr) peptide. To evaluate the effect of pr gene substitution on neutralization and ADE of DENV infection, a novel chimeric dengue virus (JEVpr/DENV2) was rationally constructed by replacing the DENV pr gene with Japanese encephalitis virus (JEV) pr gene, based on the full-length infectious complementary DNA (cDNA) clone of DENV2 ZS01/01. We found that chimeric JEVpr/DENV2 showed reduced virulence and good immunogenicity. In addition, anti-JEVpr/DENV2 sera showed broad cross-reactivity and efficient neutralizing activity with all four DENV serotypes and immature DENV2 (ImDENV2). Most importantly, compared with anti-DENV2 sera, anti-JEVpr/DENV2 sera showed significantly reduced enhancing activity of DENV infection in K562 cells. These results suggest that the ADE activities could be reduced by replacing the DENV pr gene with JEV pr gene. These findings may help us better understand the pathogenesis of DENV infection and provide a reference for the development of a vaccine against DENV. The Author(s), 2015 Dengue virus nationallicence ADE nationallicence Infectious cDNA clone nationallicence Chimeric virus nationallicence prM antibodies nationallicence Wang Ying Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut Si Lulu Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut Luo Yayan Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut Guo Xiaolan Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut Zhou Junmei Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut Fang Danyun Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut Yan Huijun Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut Zeng Gucheng Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut Jiang Lifang Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/22(2015-11-01), 9685-9698 0175-7598 99:22<9685 2015 99 253 https://doi.org/10.1007/s00253-015-6819-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6819-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wang Ying Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Si Lulu Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Luo Yayan Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Guo Xiaolan Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Zhou Junmei Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Fang Danyun Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Yan Huijun Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Zeng Gucheng Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Jiang Lifang Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/22(2015-11-01), 9685-9698 0175-7598 99:22<9685 2015 99 253