Serotype-specific anti-Dengue virus NS1 mouse antibodies cross-react with prM and are potentially involved in virus production.
Dengue virus (DENV) infection induces a strong B-cell immune response against the viral nonstructural protein 1 (NS1). Anti-NS1 antibodies (Abs) may affect virus production because they coexist with the virus in the patients' blood. The present study examined whether ten mouse monoclonal antibodies (MAbs) raised against NS1 affected production of the DENV-2. Three MAbs, 4C2, 4G11, and 4E5, showed weak neutralizing activity in a focus reduction assay. In addition, two serotype-specific MAbs, 4C2 and 4G11, protected suckling mice from lethal infection with DENV-2. An immunoprecipitation assay with DENV-2 showed that these MAbs, which were specific for the NS1 of DENV-4 and DENV-1, cross-reacted with the DENV-2 pre-membrane (prM) protein, but not with DENV-2 NS1. Interestingly, high concentrations of MAb 4G11 showed antibody-dependent enhancement of DENV-2 infection in human monocyte THP-1 cells. Taken together, these observations suggest that serotype-specific anti-NS1 MAbs are potentially involved in virus production.
Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Promsin
P
Masrinoul
Magot Diata
MD
Omokoko
Sabar
S
Pambudi
Kazuyoshi
K
Ikuta
Takeshi
T
Kurosu
D000330:Aedes; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003429:Cross Reactions / Q000276:immunology; D003715:Dengue / Q000276:immunology / Q000517:prevention & control; D003716:Dengue Virus / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; C079340:NS1 protein, Dengue virus type 2; C082515:NS1 protein, dengue-1 virus; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C074932:prM protein, Flavivirus