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 demonstrated that cellular chaperones were unable to aid the folding of p73 and suggested that ASFV may encode a chaperone. An 80-kDa protein encoded by ASFV, termed the capsid-associated protein (CAP) 80, bound to the newly synthesized capsid protein in infected cells. The 80-kDa protein was released following conformational maturation of p73 and dissociated before capsid assembly. Coexpression of the 80-kDa protein with p73 prevented aggregation and allowed the capsid protein to fold with kinetics identical to those seen in infected cells. CAP80 is, therefore, a virally encoded chaperone that facilitates capsid protein folding by masking domains exposed by the newly synthesized capsid protein, which are susceptible to aggregation, but cannot be accommodated by host chaperones. It is likely that these domains are ultimately buried when newly synthesized capsid proteins are added to the growing capsid shell.
Cobbold
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C
Department of Immunology, Institute for Animal Health, Pirbright Laboratory, Woking, Surrey GU24 ONF, United Kingdom.
Windsor
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Wileman
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T
D000358:African Swine Fever Virus / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002213:Capsid / Q000737:chemistry* / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D017510:Protein Folding; D014779:Virus Replication / Q000235:genetics
D018832:Molecular Chaperones