Jung Yong Tae, Kozak Christine A
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0460, USA.
J Virol. 2003 May;77(9):5065-72. doi: 10.1128/jvi.77.9.5065-5072.2003.
Mus spicilegus is an Eastern European wild mouse species that has previously been reported to harbor an unusual infectious ecotropic murine leukemia virus (MLV) and proviral envelope genes of a novel MLV subgroup. In the present study, M. spicilegus neonates were inoculated with Moloney ecotropic MLV (MoMLV). All 17 inoculated mice produced infectious ecotropic virus after 8 to 14 weeks, and two unusual phenotypes distinguished the isolates from MoMLV. First, most of the M. spicilegus isolates grew to equal titers on M. dunni and SC-1 cells, although MoMLV does not efficiently infect M. dunni cells. The deduced amino acid sequence of a representative clone differed from MoMLV by insertion of two serine residues within the VRA of SUenv. Modification of a molecular clone of MoMLV by the addition of these serines produced a virus that grows to high titer in M. dunni cells, establishing a role for these two serine residues in host range. A second unusual phenotype was found in only one of the M. spicilegus isolates, Spl574. Spl574 produces large syncytia of multinucleated giant cells in M. dunni cells, but its replication is restricted in other mouse cell lines. Sequencing and mutagenesis demonstrated that syncytium formation could be attributed to a single amino acid substitution within VRA, S82F. Thus, viruses with altered growth properties are selected during growth in M. spicilegus. The mutations associated with the host range and syncytium-inducing variants map to a key region of VRA known to govern interactions with the cell surface receptor, suggesting that the associated phenotypes may result from altered interactions with the unusual ecotropic virus mCAT1 receptor carried by M. dunni.
斯氏小家鼠是一种东欧野生小鼠物种，此前有报道称其携带一种不寻常的感染性亲嗜性鼠白血病病毒（MLV）以及一种新型MLV亚群的前病毒包膜基因。在本研究中，给斯氏小家鼠新生幼崽接种莫洛尼亲嗜性MLV（MoMLV）。所有17只接种的小鼠在8至14周后都产生了感染性亲嗜性病毒，并且有两种不寻常的表型将分离株与MoMLV区分开来。首先，尽管MoMLV不能有效感染邓氏小鼠细胞，但大多数斯氏小家鼠分离株在邓氏小鼠细胞和SC-1细胞上生长至相同滴度。一个代表性克隆的推导氨基酸序列与MoMLV不同，原因是在SUenv的VRA内插入了两个丝氨酸残基。通过添加这些丝氨酸对MoMLV的分子克隆进行修饰后产生了一种在邓氏小鼠细胞中生长至高滴度的病毒，这确定了这两个丝氨酸残基在宿主范围中的作用。在仅一个斯氏小家鼠分离株Spl574中发现了第二种不寻常的表型。Spl574在邓氏小鼠细胞中产生多核巨细胞的大合胞体，但其复制在其他小鼠细胞系中受到限制。测序和诱变表明，合胞体形成可归因于VRA内的单个氨基酸取代，即S82F。因此，在斯氏小家鼠中生长期间会选择具有改变生长特性的病毒。与宿主范围和合胞体诱导变体相关的突变映射到已知控制与细胞表面受体相互作用的VRA的关键区域，这表明相关表型可能是由于与邓氏小鼠携带的不寻常亲嗜性病毒mCAT1受体的相互作用改变所致。
