Homology Modelling and Structural Comparisons of Capsid-Associated Proteins from Circoviruses Reveal Important Virus-Specific Surface Antigens

Abstract

Circoviridae represent a growing family of small animal viruses. Some of these viruses have veterinary and medical importance, although, a vast amount of these newly discovered viruses have unknown effects on their hosts. The cap- sid-associated protein (Cap) of circoviruses is of interest because of its role in viral structure, immune evasion, host cell entry, and nuclear shuttling of viral components. The structure of the porcine circovirus 2 (PCV2) Cap has been solved and offered insight to these functions. Based on the crystallographic PCV2 Cap structure, models from circoviruses isolated from avian, fish, and mammalian hosts have been constructed and analyzed to better understand the roles of these proteins in the virus family. A high degree of conservation is observed in the models, however, the surface anti- gens differ among viruses. This is likely a reflection of the small genome harbored by circoviruses, and therefore the requirement of their few proteins to carry out specific vital functions, while maintaining enough variation to success- fully infect their hosts. Here we describe the putative structures of a range of Cap proteins from circoviruses based on the crystallographic determination of porcine Cap, identifying key regions for function and inhibition of crystal forma- tion.