We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Antibodies against the Envelope Glycoprotein Promote Infectivity of Immature Dengue Virus Serotype 2.
- Authors
Voorham, Júlia M. da Silva; Rodenhuis-Zybert, Izabela A.; Nuñez, Nilda Vanesa Ayala; Colpitts, Tonya M.; Ende-Metselaar, Heidi van der; Fikrig, Erol; Diamond, Michael S.; Wilschut, Jan; Smit, Jolanda M.
- Abstract
Cross-reactive dengue virus (DENV) antibodies directed against the envelope (E) and precursor membrane (prM) proteins are believed to contribute to the development of severe dengue disease by facilitating antibody-dependent enhancement of infection. We and others recently demonstrated that anti-prM antibodies render essentially non-infectious immature DENV infectious in Fcc-receptor-expressing cells. Immature DENV particles are abundantly present in standard (st) virus preparations due to inefficient processing of prM to M during virus maturation. Structural analysis has revealed that the E protein is exposed in immature particles and this prompted us to investigate whether antibodies to E render immature particles infectious. To this end, we analyzed the enhancing properties of 27 anti-E antibodies directed against distinct structural domains. Of these, 23 bound to immature particles, and 15 enhanced infectivity of immature DENV in a furindependent manner. The significance of these findings was subsequently tested in vivo using the well-established West Nile virus (WNV) mouse model. Remarkably, mice injected with immature WNV opsonized with anti-E mAbs or immune serum produced a lethal infection in a dose-dependent manner, whereas in the absence of antibody immature WNV virions caused no morbidity or mortality. Furthermore, enhancement infection studies with standard (st) DENV preparations opsonized with anti-E mAbs in the presence or absence of furin inhibitor revealed that prM-containing particles present within st virus preparations contribute to antibody-dependent enhancement of infection. Taken together, our results support the notion that antibodies against the structural proteins prM and E both can promote pathogenesis by enhancing infectivity of prMcontaining immature and partially mature flavivirus particles.
- Subjects
GLYCOPROTEINS; DENGUE viruses; SEROTYPES; WEST Nile virus; LABORATORY mice; FLAVIVIRUSES
- Publication
PLoS ONE, 2012, Vol 7, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0029957