 Ratna Wijaya
Visiting Research Fellow in Microbiology and Immunology Department
NUS |
Title:
Role of non-structural protein 1 glycosylation in dengue virus fitness and virulence
Abstract:
The non-structural protein 1 (NS1) of dengue virus (DENV) is a highly conserved 46-55 kDa protein which contains two N-glycosylation sites at positions 130 and 207 (N130 and N207). Secreted hexameric NS1 (sNS1) has been proposed to play an important role in dengue pathogenesis. However, the role of the two N-glycans in NS1’s biological functions has not been carefully examined. In this study, we generated stable DENV mutants that lack glycan structures at either N sites of NS1 and subsequently determined the in vitro and in vivo fitness in cell lines and symptomatic animal model, respectively. We show that the lack of glycan at either N sites of NS1 did not impair the structure, conformation, and lipid cargo of the hexameric sNS1 as well as the replication and growth of the virus in both mosquito and mammalian cell lines. However, while the N130 de-glycosylated mutant displayed a parental in vivo fitness in IFNAR-/- mice, the N207 de-glycosylated mutant was significantly attenuated as evidenced by higher survival rate and faster clearance of the virus in circulation, compared to the WT virus. Further experiment revealed that infection with N207 de-glycosylated mutant induces a lower initial inflammatory host response. Our results suggested that the glycans at position N207 but not N130 on NS1, play an important role in DENV in vivo fitness and virulence, by modulating the initial inflammatory response.
Biography:
Ratna Sari Wijaya is a visiting research fellow in Professor Sylvie Alonso’s Lab at the Department of Microbiology and Immunology, National University of Singapore. Her current research aims to understand the molecular mechanisms underlying dengue virus attenuation by non-structural 1 (NS1) protein glycosylation deficiency.
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