Kontou Maria, Govindasamy Lakshmanan, Nam Hyun-Joo, Bryant Nathan, Llamas-Saiz Antonio L, Foces-Foces Concepción, Hernando Eva, Rubio Mari-Paz, McKenna Robert, Almendral José M, Agbandje-McKenna Mavis
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, 32610-0245, USA.
J Virol. 2005 Sep;79(17):10931-43. doi: 10.1128/JVI.79.17.10931-10943.2005.
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.
小鼠细小病毒（MVM）的两种毒株，即免疫抑制性毒株（MVMi）和原型毒株（MVMp），在体外嗜性和体内致病性方面表现出不同。我们报告了MVMp病毒样颗粒（MVMp(b)）和天然野生型（wt）空衣壳（MVMp(e)）的晶体结构，分辨率分别确定并精修至3.25 Å和3.75 Å，还将它们与MVMi的结构进行了比较，本研究中MVMi的结构分辨率也精修至3.5 Å。对MVMp(b)和MVMp(e)衣壳的比较表明它们的结构相同，提供了结构验证，即一些异源表达的细小病毒衣壳与宿主细胞中产生的wt衣壳无法区分。MVMi和MVMp衣壳的结构几乎相同，但局部表面构象差异集中在来自三个特定结构域的对称相关衣壳蛋白处：（i）二十面体五重轴；（ii）二十面体三重轴处突起的“肩部”；（iii）二十面体二重轴处凹陷周围的区域。后两个结构域包含MVM体外嗜性的重要决定因素（残基317和321）以及赋予MVMi纤维嗜性的正向突变残基（残基399、460、553和558）。此外，MVM毒株之间的这些结构差异与其他自主细小病毒衣壳所定位的嗜性和致病性决定因素共定位，突出了细小病毒衣壳共同区域在控制病毒 - 宿主相互作用中的重要性。
