title: Structural determinants of tissue tropism and in vivo pathogenicity for the parvovirus minute virus of mice.
abstract: Two strains of the parvovirus minute virus of mice (MVM), the immunosuppressive (MVMi) and the prototype (MVMp) strains, display disparate in vitro tropism and in vivo pathogenicity. We report the crystal structures of MVMp virus-like particles (MVMp(b)) and native wild-type (wt) empty capsids (MVMp(e)), determined and refined to 3.25 and 3.75 A resolution, respectively, and their comparison to the structure of MVMi, also refined to 3.5 A resolution in this study. A comparison of the MVMp(b) and MVMp(e) capsids showed their structures to be the same, providing structural verification that some heterologously expressed parvovirus capsids are indistinguishable from wt capsids produced in host cells. The structures of MVMi and MVMp capsids were almost identical, but local surface conformational differences clustered from symmetry-related capsid proteins at three specific domains: (i) the icosahedral fivefold axis, (ii) the "shoulder" of the protrusion at the icosahedral threefold axis, and (iii) the area surrounding the depression at the icosahedral twofold axis. The latter two domains contain important determinants of MVM in vitro tropism (residues 317 and 321) and forward mutation residues (residues 399, 460, 553, and 558) conferring fibrotropism on MVMi. Furthermore, these structural differences between the MVM strains colocalize with tropism and pathogenicity determinants mapped for other autonomous parvovirus capsids, highlighting the importance of common parvovirus capsid regions in the control of virus-host interactions.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, 32610-0245, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Kontou
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Govindasamy
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Nam
authors.forename: Nathan
authors.initials: N
authors.lastname: Bryant
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Llamas-Saiz
authors.forename: Concepción
authors.initials: C
authors.lastname: Foces-Foces
authors.forename: Eva
authors.initials: E
authors.lastname: Hernando
authors.forename: Mari-Paz
authors.initials: MP
authors.lastname: Rubio
authors.forename: Robert
authors.initials: R
authors.lastname: McKenna
authors.forename: José M
authors.initials: JM
authors.lastname: Almendral
authors.forename: Mavis
authors.initials: M
authors.lastname: Agbandje-McKenna
mesh_terms: D002213:Capsid / Q000737:chemistry; D036022:Capsid Proteins / Q000737:chemistry; D008915:Minute Virus of Mice / Q000737:chemistry* / Q000472:pathogenicity / Q000502:physiology; D008958:Models, Molecular; D011487:Protein Conformation; D018523:Tropism; D014774:Virulence
chemical_list: D036022:Capsid Proteins