期刊
CELLULAR MICROBIOLOGY
卷 12, 期 4, 页码 453-472出版社
WILEY
DOI: 10.1111/j.1462-5822.2009.01407.x
关键词
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资金
- Biomedical Research Council, Singapore [BMRC/06/1/21/19/451]
- National University of Singapore [R-182-000-115-112]
P>The Flaviviridae family consists of several medically important pathogens such as West Nile virus (WNV) and Dengue virus (DENV). Flavivirus capsid (C) protein is a key structural component of virus particles. However, the role of C protein in the pathogenesis of arthropod-borne flaviviruses is poorly understood. To examine whether flavivirus C protein can associate with cellular proteins, and contribute to viral pathogenesis, WNV/DENV C protein was screened against a human brain/liver cDNA yeast two-hybrid library. This study identified human Sec3 exocyst protein (hSec3p) as a novel interacting partner of WNV and DENV C protein. Mutagenesis studies showed that the SH2 domain-binding motif of hSec3p binds to the first 15 amino acids of C protein. We report for the first time that hSec3p can modulate virus production by affecting viral RNA transcription and translation through the sequestration of elongation factor 1 alpha (EF1 alpha). This molecular discovery shed light on the protective role of hSec3p during flavivirus infection. This study also highlighted the antagonistic mechanism adopted by flavivirus C protein that can negatively regulate the formation of hSec3p-EF1 alpha complex by sequestering hSec3p to establish successful infection.
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