development and characterization of a reverse genetic system for studying dengue virus serotype 3 strain variation and neutralization反向遗传系统的发展和特征研究登革3型病毒毒株的变异和中和.pdfVIP

Development and Characterization of a Reverse Genetic System for Studying Dengue Virus Serotype 3 Strain Variation and Neutralization 1 2 3 2 2 William B. Messer , Boyd Yount , Kari E. Hacker , Eric F. Donaldson , Jeremy P. Huynh , Aravinda M. de 3 2 Silva *, Ralph S. Baric * 1 Division of Infectious Diseases, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America, 2 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America, 3 Department of Microbiology and Immunology, and Southeast Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America Abstract Dengue viruses (DENV) are enveloped single-stranded positive-sense RNA viruses transmitted by Aedes spp. mosquitoes. There are four genetically distinct serotypes designated DENV-1 through DENV-4, each further subdivided into distinct genotypes. The dengue scientific community has long contended that infection with one serotype confers lifelong protection against subsequent infection with the same serotype, irrespective of virus genotype. However this hypothesis is under increased scrutiny and the role of DENV genotypic variation in protection from repeated infection is less certain. As dengue vaccine trials move increasingly into field-testing, there is an urgent need to develop tools to better define the role of genotypic variation in DENV infection and immunity. To better understand genotypic variation in DENV-3 neutraliz