RESUMO
IMPORTANCE: Previously, we modeled direct transmission chains of Zika virus (ZIKV) by serially passaging ZIKV in mice and mosquitoes and found that direct mouse transmission chains selected for viruses with increased virulence in mice and the acquisition of non-synonymous amino acid substitutions. Here, we show that these same mouse-passaged viruses also maintain fitness and transmission capacity in mosquitoes. We used infectious clone-derived viruses to demonstrate that the substitution in nonstructural protein 4A contributes to increased virulence in mice.
Assuntos
Culicidae , Aptidão Genética , Mosquitos Vetores , Virulência , Zika virus , Animais , Camundongos , Culicidae/virologia , Mosquitos Vetores/virologia , Virulência/genética , Zika virus/química , Zika virus/genética , Zika virus/patogenicidade , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia , Inoculações Seriadas , Substituição de Aminoácidos , Aptidão Genética/genéticaRESUMO
The Zika virus outbreak in the Americas has caused global concern. To help accelerate this fight against Zika, we launched the OpenZika project. OpenZika is an IBM World Community Grid Project that uses distributed computing on millions of computers and Android devices to run docking experiments, in order to dock tens of millions of drug-like compounds against crystal structures and homology models of Zika proteins (and other related flavivirus targets). This will enable the identification of new candidates that can then be tested in vitro, to advance the discovery and development of new antiviral drugs against the Zika virus. The docking data is being made openly accessible so that all members of the global research community can use it to further advance drug discovery studies against Zika and other related flaviviruses.