title: The magnitude of dengue virus NS1 protein secretion is strain dependent and does not correlate with severe pathologies in the mouse infection model.
abstract: There are conflicting data on the relationship between the level of secreted NS1 (sNS1), viremia, and disease severity upon dengue virus (DENV) infection in the clinical setting, and therefore, we examined this relationship in the widely accepted AG129 mouse model. Because of the failure of a routinely used NS1 detection kit to detect sNS1 of the mouse-adapted DENV2 strain, we screened 15 previously undescribed NS1 monoclonal antibodies and developed a robust capture enzyme-linked immunosorbent assay (ELISA) with detection sensitivity at the low nanogram level (0.2 ng/ml) using recombinant baculovirus-expressed sNS1 as well as sNS1 that was immunoaffinity purified from the various DENV2 strains employed in this study. Using this test, we demonstrated that increased viremia paralleled severe pathologies; however, sNS1 level did not correlate with viremia or severity. Furthermore, among the DENV2 strains that were tested, the level of NS1 secretion did not correspond to virus replication rate in vitro, at the cellular level. Together, our data indicate that the magnitude of NS1 secretion appears to be strain dependent and does not correlate with viral virulence in the AG129 mouse model.
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Satoru
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kah Hin
authors.initials: KH
authors.lastname: Tan
authors.forename: Abhay P S
authors.initials: AP
authors.lastname: Rathore
authors.forename: Kathryn
authors.initials: K
authors.lastname: Rozen-Gagnon
authors.forename: Wang
authors.initials: W
authors.lastname: Shuai
authors.forename: Christiane
authors.initials: C
authors.lastname: Ruedl
authors.forename: Subhash G
authors.initials: SG
authors.lastname: Vasudevan
mesh_terms: D000330:Aedes; D000818:Animals; D002460:Cell Line; D003715:Dengue / Q000473:pathology* / Q000821:virology; D003716:Dengue Virus / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D057507:Mice, 129 Strain; D013045:Species Specificity; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: C079340:NS1 protein, Dengue virus type 2; D017361:Viral Nonstructural Proteins