The pestivirus Erns glycoprotein interacts with E2 in both infected cells and mature virions. Virology 314:696–705

Erns is a pestivirus envelope glycoprotein indispensable for virus attachment and infection of target cells. Unlike the other two envelope proteins E1 and E2, Erns lacks a transmembrane domain and a vast quantity is secreted into the medium of infected cells. The protein is also present in fractions of pure pestivirus virions, raising the important and intriguing question regarding the mechanism of its attachment to the pestivirus envelope. In this study a direct interaction between Erns and E2 glycoproteins was demonstrated in both pestivirus-infected cells and mature virions. By co- and sequential immunoprecipitation we showed that an Erns-E2 heterodimer is assembled very early after translation of the viral polyprotein and before its processing is completed. Our results suggest that Erns is attached to the pestivirus envelope via a direct interaction with E2 and explain the role of Erns in the initial virus–target cell interaction