Structural studies of Chikungunya virus-like particles complexed with human antibodies: Neutralization and cell-to-cell transmission
Autor(es): Porta Jason, Mangala Prasad Vidya, Wang Cheng-I, Akahata Wataru, Ng Lisa F P, Rossmann Michael G
Resumo: Chikungunya virus is a positive-str-ed RNA alphavirus. Structures of chikungunya virus-like particles in complex with strongly neutralizing antibody Fab fragments (8B10 - 5F10) were determined using cryo-electron microscopy - X-ray crystallography. By fitting the crystallographically determined structures of these Fab fragments into the cryo-electron density maps, we show that Fab fragments of antibody 8B10 extend radially from the viral surface - block receptor binding on the E2 glycoprotein. In contrast, Fab fragments of antibody 5F10 bind the tip of the E2 B domain - lie tangentially on the viral surface. Fab 5F10 fixes the B domain rigidly to the surface of the virus, blocking exposure of the fusion loop on glycoprotein E1 - therefore preventing the virus from becoming fusogenic. Although Fab 5F10 can neutralize the wild-type virus, it can also bind to a mutant virus without inhibiting fusion or attachment. Although the mutant virus is no longer able to propagate by extracellular budding, it can, however, enter the next cell by traveling through junctional complexes without being intercepted by a neutralizing antibody to the wild-type virus, thus clarifying how cell-to-cell transmission can occur. Alphaviral infections are transmitted mainly by mosquitoes. Chikungunya virus (CHIKV), which belongs to the Alphavirus genus, has a wide distribution in the Old World that has exp-ed in recent years into the Americas. There are currently no vaccines or drugs against alphaviral infections. Therefore, a better underst-ing of CHIKV - its associated neutralizing antibodies will aid in the development of effective treatments.
Imprenta: Journal of Virology, v. 90, n. 3, p. 1169-1177, 2015
Identificador do objeto digital: 10.1128/JVI.02364-15
Descritores: Chikungunya virus - Cell ; Chikungunya virus - RNA ; Chikungunya virus - Antibodies ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Transmission ; Chikungunya virus - Vaccine ; Chikungunya virus - Immunology
Data de publicação: 2015
