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Zika virus is a member of the Flavivirus genus that had not been associated with severe disease in humans until the recent outbreaks, when it was linked to microcephaly in newborns in Brazil and to Guillain-Barre syndrome in adults in French Polynesia. Zika virus is related to dengue virus, and here we report that a subset of antibodies targeting a conformational epitope isolated from patients with dengue virus also potently neutralize Zika virus. The crystal structure of two of these antibodies in complex with the envelope protein of Zika virus reveals the details of a conserved epitope, which is also the site of interaction of the envelope protein dimer with the precursor membrane (prM) protein during virus maturation. Comparison of the Zika and dengue virus immunocomplexes provides a lead for rational, epitope-focused design of a universal vaccine capable of eliciting potent cross-neutralizing antibodies to protect simultaneously against both Zika and dengue virus infections., Zika virus (ZIKV) is an arthropod-borne enveloped virus belonging to the Flavivirus genus in the family Flaviviridae, which also includes the human pathogenic yellow fever, dengue, West Nile and tick-borne [...]

Dengue disease is caused by four different flavivirus (1) serotypes, which infect 390 million people yearly with 25% symptomatic cases (2) and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype 2 (refs 3,4). Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies (5,6). We recently isolated human antibodies potently neutralizing all four dengue virus serotypes (7). Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop (8) and the two conserved glycan chains. This 'E-dimer-dependent epitope' is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell (9), explaining its conservation across serotypes and highlighting an Achilles' heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus., Exposed at the surface of infectious mature dengue virus (DENV) particles, protein E is the sole target of neutralizing antibodies. It displays an icosahedral arrangement in which 90 E dimers [...]

Little is known about the three-dimensional organization of rubella virus, which causes a relatively mild measles-like disease in children but leads to serious congenital health problems when contracted in utero [...]

Author(s): Giovanna Barba-Spaeth; Wanwisa Dejnirattisai; Alexander Rouvinski; Marie-Christine Vaney; Iris Medits; Arvind Sharma; Etienne Simon-Lorire; Anavaj Sakuntabhai; Van-Mai Cao-Lormeau; Ahmed Haouz; Patrick England; Karin Stiasny; Juthathip Mongkolsapaya; Franz X. Heinz; [...]