Friedrich R, Friedrich U, Maennle G
Division of Molecular Oncology, Justus Liebig University, Giessen, Germany.
Virology. 1991 Jul;183(1):343-50. doi: 10.1016/0042-6822(91)90147-4.
The replication-defective Friend spleen focus-forming virus (F-SFFV) induces acute erythroblastosis in adult mice. The envelope-related (env) gene and LTR are the only functional elements of the viral genome. The env-coded glycoprotein gp55 has been shown to be responsible for target cell specificity and for the short latency of the disease caused by SFFV. This molecule closely resembles the env coded proteins gp70 + p15E of mink cell focus inducing viruses (MCFV). The only substantial differences between these two env genes are a large deletion spanning 585 nucleotides in the middle of the F-SFFV gene and a frameshift mutation near the 3' end leading to a modified and shortened membrane anchor in the mature protein. To determine if the large deletion and/or the frameshift mutation are capable of changing the properties of a nonpathogenic MCFV into those of an acutely pathogenic SFFV we introduced these changes into the env gene of an MCFV. The results show that the mutated MCFV is as acutely pathogenic as F-SFFV. We therefore conclude that the modified membrane anchor of gp55 and the change caused by the large deletion are the essential determinants of the high pathogenicity of SFFV.
复制缺陷型弗氏脾集落形成病毒（F-SFFV）可在成年小鼠中诱发急性成红细胞增多症。包膜相关（env）基因和长末端重复序列（LTR）是病毒基因组仅有的功能元件。已证明env编码的糖蛋白gp55决定靶细胞特异性以及由SFFV引起的疾病的短潜伏期。该分子与水貂细胞集落诱导病毒（MCFV）的env编码蛋白gp70 + p15E极为相似。这两个env基因之间唯一显著的差异是F-SFFV基因中部有一个跨越585个核苷酸的大片段缺失，以及3'端附近的一个移码突变，导致成熟蛋白中的膜锚定结构发生改变并缩短。为了确定该大片段缺失和/或移码突变是否能够将无致病性的MCFV的特性转变为急性致病性SFFV的特性，我们将这些变化引入了MCFV的env基因。结果表明，突变后的MCFV与F-SFFV一样具有急性致病性。因此，我们得出结论，gp55修饰后的膜锚定结构以及大片段缺失所导致的变化是SFFV高致病性的关键决定因素。
