Replacement of pr gene with Japanese encephalitis virus pr using reverse genetics reduces antibody-dependent enhancement of dengue virus 2 infection

Verfasser / Beitragende:
[Ying Wang, Lulu Si, Yayan Luo, Xiaolan Guo, Junmei Zhou, Danyun Fang, Huijun Yan, Gucheng Zeng, Lifang Jiang]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/22(2015-11-01), 9685-9698
Format:
Artikel (online)
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024 7 0 |a 10.1007/s00253-015-6819-3  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-015-6819-3 
245 0 0 |a Replacement of pr gene with Japanese encephalitis virus pr using reverse genetics reduces antibody-dependent enhancement of dengue virus 2 infection  |h [Elektronische Daten]  |c [Ying Wang, Lulu Si, Yayan Luo, Xiaolan Guo, Junmei Zhou, Danyun Fang, Huijun Yan, Gucheng Zeng, Lifang Jiang] 
520 3 |a 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. 
540 |a The Author(s), 2015 
690 7 |a Dengue virus  |2 nationallicence 
690 7 |a ADE  |2 nationallicence 
690 7 |a Infectious cDNA clone  |2 nationallicence 
690 7 |a Chimeric virus  |2 nationallicence 
690 7 |a prM antibodies  |2 nationallicence 
700 1 |a Wang  |D Ying  |u 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  |4 aut 
700 1 |a Si  |D Lulu  |u 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  |4 aut 
700 1 |a Luo  |D Yayan  |u 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  |4 aut 
700 1 |a Guo  |D Xiaolan  |u 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  |4 aut 
700 1 |a Zhou  |D Junmei  |u 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  |4 aut 
700 1 |a Fang  |D Danyun  |u 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  |4 aut 
700 1 |a Yan  |D Huijun  |u 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  |4 aut 
700 1 |a Zeng  |D Gucheng  |u 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  |4 aut 
700 1 |a Jiang  |D Lifang  |u 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  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/22(2015-11-01), 9685-9698  |x 0175-7598  |q 99:22<9685  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-015-6819-3  |q text/html  |z Onlinezugriff via DOI 
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900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-015-6819-3  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Ying  |u 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  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Si  |D Lulu  |u 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  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Luo  |D Yayan  |u 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  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Guo  |D Xiaolan  |u 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  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhou  |D Junmei  |u 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  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Fang  |D Danyun  |u 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  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Yan  |D Huijun  |u 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  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zeng  |D Gucheng  |u 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  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Jiang  |D Lifang  |u 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  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/22(2015-11-01), 9685-9698  |x 0175-7598  |q 99:22<9685  |1 2015  |2 99  |o 253