Structure of an Enteric Pathogen, Bovine Parvovirus

Abstract

Bovine parvovirus (BPV), the causative agent of respiratory and gastrointestinal disease in cows, is the type member of the Bocaparvovirus genus of the Parvoviridae family. Toward efforts to obtain a template for the development of vaccines and small-molecule inhibitors for this pathogen, the structure of the BPV capsid, assembled from the major capsid viral protein 2 (VP2), was determined using X-ray crystallography as well as cryo-electron microscopy and three-dimensional image reconstruction (cryoreconstruction) to 3.2-and 8.8-Å resolutions, respectively. The VP2 region ordered in the crystal structure, from residues 39 to 536, conserves the parvoviral eight-stranded jellyroll motif and an ␣A helix. The BPV capsid displays common parvovirus features: a channel at and depressions surrounding the 5-fold axes and protrusions surrounding the 3-fold axes. However, rather than a depression centered at the 2-fold axes, a raised surface loop divides this feature in BPV. Additional observed density in the capsid interior in the cryo-reconstructed map, compared to the crystal structure, is interpreted as 10 additional N-terminal residues, residues 29 to 38, that radially extend the channel under the 5-fold axis, as observed for human bocavirus 1 (HBoV1). Surface loops of various lengths and conformations extend from the core jellyroll motif of VP2. These loops confer the unique surface topology of the BPV capsid, making it strikingly different from HBoV1 as well as the type members of other Parvovirinae genera for which structures have been determined. For the type members, regions structurally analogous to those decorating the BPV capsid surface serve as determinants of receptor recognition, tissue and host tropism, pathogenicity, and antigenicity. IMPORTANCEBovine parvovirus (BPV), identified in the 1960s in diarrheic calves, is the type member of the Bocaparvovirus genus of the nonenveloped, single-stranded DNA (ssDNA) Parvoviridae family. The recent isolation of human bocaparvoviruses from children with severe respiratory and gastrointestinal infections has generated interest in understanding the life cycle and pathogenesis of these emerging viruses. We have determined the high-resolution structure of the BPV capsid assembled from its predominant capsid protein VP2, known to be involved in a myriad of functions during host cell entry, pathogenesis, and antigenicity for other members of the Parvovirinae. Our results show the conservation of the core secondary structural elements and the location of the N-terminal residues for the known bocaparvovirus capsid structures. However, surface loops with high variability in sequence and conformation give BPV a unique capsid surface topology. Similar analogous regions in other Parvovirinae type members are important as determinants of receptor recognition, tissue and host tropism, pathogenicity, and antigenicity. B ovine parvovirus (BPV), the type member of the Bocaparvovirus genus of the Parvoviridae family, was discovered in 1961 in the gastrointestinal tract of di...

Structural Insights into Human Bocaparvoviruses

“…2B and 3A). This unique feature, reported previously for the crystal structure of BPV (39), for HBoV1 at 7.9-Å resolution (33), and low-resolution structures determined for the HBoV-Fab complexes (34), has not been observed in any other non-bocaparvovirus capsid structures determined to date.…”

“…A comparison of these viruses identified differences in the specific variable loop regions between the secondary structure elements forming the surface of the capsids, particularly variable region I (VR-I) to VR-V and VR-VIIIB previously defined for autonomous parvoviruses (38). Compared to the crystal structure of BPV, differences were identified in all 10 reported VRs, VR-I to VR-IX (39). These VRs are important determinants of parvovirus infectivity, transduction efficiency, and antigenicity (39).…”

“…Compared to the crystal structure of BPV, differences were identified in all 10 reported VRs, VR-I to VR-IX (39). These VRs are important determinants of parvovirus infectivity, transduction efficiency, and antigenicity (39). Structural comparisons identified VR-III as a potential determinant of the tissue tropism of HBoVs and VR-VI to VR-VIII as well as VR-IX as potential determinants of bocaparvovirus host tropism.…”

Genetic characterization of feline bocavirus detected in cats in Japan

“…The ORF3 gene is unique and has not been detected in parvoviruses other than BoV [14]. BoV infections have been confirmed in humans, mice, dogs, pigs, cows, and California sea lions [2,[4][5][6]8]. A number of clinical symptoms occur in BoV-infected hosts.…”

Cryo-EM maps reveal five-fold channel structures and their modification by gatekeeper mutations in the parvovirus minute virus of mice (MVM) capsid

“…Both panels show the structure oriented with five-fold axis positioned at the left (axes indicated, lower right). (C) The known crystal structures of other related parvoviruses CPV (PDB ID 1C8D; Simpson et al, 2000) (Pink), FPV (PDB ID 1C8E; Simpson et al, 2000) (Green), B19 (PDB ID 1S58; Kaufmann et al, 2004) (Blue), and BPV (PDB ID: 4QC8; Kailasan et al, 2015) (Orange) were superimposed to show that the VP2 N-termini of parvoviruses have not been visualized before.…”