Porcine circovirus 2 (PCV2) is the smallest autonomously replicating virus and thus defines the minimum amount of genetic and biochemical information needed for infection. PCV2 infects nearly every tissue within its host, and infections result in immunosuppression and subsequent death of the host. Infection is initiated via the attachment of the PCV2 capsid to heparan sulfate and chondroitin sulfate B glycosaminoglycan (GAG) on the surface of the cell. We demonstrate that the PCV2 capsid does not recognize the pyranose backbone of a GAG, and solely interacts with the sulfates of GAG. We visualize the interaction between heparin sulfate, an analog for heparan sulfate, and the PCV2 capsid using cryo-electron micr... More
Porcine circovirus 2 (PCV2) is the smallest autonomously replicating virus and thus defines the minimum amount of genetic and biochemical information needed for infection. PCV2 infects nearly every tissue within its host, and infections result in immunosuppression and subsequent death of the host. Infection is initiated via the attachment of the PCV2 capsid to heparan sulfate and chondroitin sulfate B glycosaminoglycan (GAG) on the surface of the cell. We demonstrate that the PCV2 capsid does not recognize the pyranose backbone of a GAG, and solely interacts with the sulfates of GAG. We visualize the interaction between heparin sulfate, an analog for heparan sulfate, and the PCV2 capsid using cryo-electron microscopy. The image reconstructions provide the first example of an asymmetric distribution of heparin sulfate on the surface of a virus capsid. We demonstrate that each subunit possesses six heparin sulfate binding sites, but binding at any site occludes binding at the other five sites. The binding sites are defined by arginine, lysine, and polar amino acids. Mutation of these arginine and lysine to alanine diminishes the binding capacity of the PCV2 to heparin sulfate. A third to two-thirds of the binding sites (subunits) in each PCV2 is occupied by segments of one or multiple 12kDa heparin sulfate chains –leaving the remaining subunits unliganded. We discuss the significance of the unliganded subunits in the life cycle of PCV2.
