A virally encoded chaperone specialized for folding of the major capsid protein of African swine fever virus

It is generally believed that cellular chaperones facilitate the folding of virus capsid proteins, or that capsid proteins fold spontaneously. Here we show that p73, the major capsid protein of African swine fever virus (ASFV ) failed to fold and aggregated when expressed alone in cells. This demonst rated that cellular chaperones were unable to aid the folding of p73 and su ggested that ASFV may encode a chaperone. An 80-kDa protein encoded by ASFV , termed the capsid-associated protein (CAP) 80, bound to the newly synthes ized capsid protein in infected cells. The 80-kDa protein was released foll owing conformational maturation of p73 and dissociated before capsid assemb ly. Coexpression of the 80-kDa protein with p73 prevented aggregation and a llowed the capsid protein to fold with kinetics identical to those seen in infected cells. CAP80 is, therefore, a virally encoded chaperone that facil itates capsid protein folding by masking domains exposed by the newly synth esized capsid protein, which are susceptible to aggregation, but cannot be accommodated by host chaperones. It is likely that these domains are ultima tely buried when newly synthesized capsid proteins are added to the growing capsid shell.