Structural changes of envelope proteins during alphavirus fusion

The pH-sensitive mechanism that gets alphaviruses into host cells Alphaviruses are significant animal and human pathogens — as demonstrated in recent outbreaks of infection with the mosquito-borne Chikungunya virus in India and southeast Asia. The E1 and E2 glycoproteins of alphaviruses are central to the way the virus infects host cells. The E1/E2 heterodimers that form spikes on the virus surface dissociate in the acidic conditions found in the internal vesicles of host cells, and E1 triggers infection by fusing with the endosomal membrane. Félix Rey and colleagues present the structure of Chikungunya virus envelope glycoprotein at neutral pH, and Michael Rossmann and colleagues reveal the structure of the envelope proteins of Sindbis virus at low pH. Sindbis virus can cause fever in humans and is the most extensively studied alphavirus. Comparison of the two structures provides insight into how fusion activation is controlled and points to possible vaccine targets.