Seth Shaguna, Skountzou Ioanna, Gernert Kim M, Compans Richard W
Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA.
J Virol. 2007 Apr;81(8):4286-97. doi: 10.1128/JVI.01623-06. Epub 2007 Feb 7.
SER virus is a type 5 parainfluenza virus that does not exhibit syncytium formation, in contrast to most other paramyxoviruses. This property has been attributed, at least in part, to the presence of an extension of the cytoplasmic tail (CT) of the SER F protein, as truncations or mutations of this region resulted in enhanced fusion. In this study we used repeated passage to select for mutant SER viruses, which were found to be fusogenic. The mutant viruses replicated at levels comparable to or higher than the wild-type SER virus and caused plaque formation, in contrast to the wild-type virus which does not form plaques. The mutants differed strikingly in their plaque sizes. The F genes of mutant viruses were cloned and sequenced and shared some mutations, including a proline-to-leucine change at position 22 and an isoleucine-to-leucine substitution at position 191; other changes that were specific to each mutant were also found. The HN proteins of mutant viruses also showed mutations spanning the length of the protein whereas the M protein showed a consistent mutation, threonine to isoleucine, at position 129. The structure of the F protein was used to identify residues involved in the mutant phenotypes in terms of their location and proximity to heptad repeat domains.
SER病毒是一种5型副流感病毒，与大多数其他副粘病毒不同，它不会形成多核体。这种特性至少部分归因于SER F蛋白细胞质尾（CT）的延伸，因为该区域的截断或突变会导致融合增强。在本研究中，我们通过反复传代筛选出了具有融合性的突变型SER病毒。与不形成噬斑的野生型病毒相比，突变型病毒的复制水平与野生型SER病毒相当或更高，并导致噬斑形成。突变体的噬斑大小差异显著。对突变型病毒的F基因进行了克隆和测序，发现它们有一些共同的突变，包括第22位脯氨酸到亮氨酸的变化以及第191位异亮氨酸到亮氨酸的替换；还发现了每个突变体特有的其他变化。突变型病毒的HN蛋白也显示出贯穿整个蛋白长度的突变，而M蛋白在第129位显示出一致的突变，苏氨酸变为异亮氨酸。利用F蛋白的结构，根据其位置和与七肽重复结构域的接近程度，确定了与突变表型相关的残基。
