期刊
VIROLOGY
卷 406, 期 2, 页码 328-335出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2010.07.024
关键词
Dengue virus; Flavivirus; Envelope protein; Domain III; FG loop; Mosquitoes; Mutagenesis
类别
资金
- Centers for Disease Control and Prevention
- Pediatric Dengue Vaccine Initiative (PDVI) [TR-159A]
- College of Veterinary Medicine and Biomedical Sciences Research Council
The FG extended loop in domain Ill of the dengue virus type 2 (DENV2) envelope protein is postulated to be a molecular determinant for host cell infectivity. To determine the contribution of the FG loop to virus infectivity, an infectious cDNA clone of DENV2 was manipulated by deleting amino acids in the loop (VEPG Delta) to mimic tick-borne flaviviruses or by substituting these AAs with RGD or RGDK/S to mimic motifs present in other mosquito-borne flaviviruses. We found the FG loop to be dispensable for infection of C6/36 cells but critical for infection of Aedes aegypti mosquito midguts and mammalian cells. All the FG loop mutants were able to bind to and enter mammalian cells but replication of VEPG Delta in Vero cells at 37 degrees C was delayed until acquisition of secondary mutations. Reduced binding of DENV2 type-specific monoclonal antibody 3H5 to mutant viruses confirmed the FG loop motif as its target epitope. (C) 2010 Elsevier Inc. All rights reserved.
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