Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China.
Viruses. 2019 Jan 31;11(2):130. doi: 10.3390/v11020130.
Foamy viruses (FVs) have extensive cell tropism in vitro, special replication features, and no clinical pathogenicity in naturally or experimentally infected animals, which distinguish them from orthoretroviruses. Among FVs, bovine foamy virus (BFV) has undetectable or extremely low levels of cell-free transmission in the supernatants of infected cells and mainly spreads by cell-to-cell transmission, which deters its use as a gene transfer vector. Here, using an in vitro virus evolution system, we successfully isolated high-titer cell-free BFV strains from the original cell-to-cell transmissible BFV3026 strain and further constructed an infectious cell-free BFV clone called pBS-BFV-Z1. Following sequence alignment with a cell-associated clone pBS-BFV-B, we identified a number of changes in the genome of pBS-BFV-Z1. Extensive mutagenesis analysis revealed that the C-terminus of envelope protein, especially the K898 residue, controls BFV cell-free transmission by enhancing cell-free virus entry but not the virus release capacity. Taken together, our data show the genetic determinants that regulate cell-to-cell and cell-free transmission of BFV.
泡沫病毒（FV）在体外具有广泛的细胞嗜性、特殊的复制特征，并且在自然或实验感染的动物中没有临床致病性，这使它们有别于正逆转录病毒。在 FV 中，牛泡沫病毒（BFV）在感染细胞的上清液中无细胞游离形式或极低水平的游离传播，主要通过细胞间传播传播，这阻碍了其作为基因转移载体的使用。在这里，我们使用体外病毒进化系统，成功地从原始的细胞间可传播 BFV3026 株中分离出高滴度的无细胞 BFV 株，并进一步构建了一种称为 pBS-BFV-Z1 的感染性无细胞 BFV 克隆。与细胞相关的克隆 pBS-BFV-B 进行序列比对后，我们发现 pBS-BFV-Z1 的基因组中有许多变化。广泛的诱变分析表明，包膜蛋白的 C 末端，特别是 K898 残基，通过增强无细胞病毒进入而不是病毒释放能力来控制 BFV 的无细胞传播。总之，我们的数据显示了调节 BFV 细胞间和无细胞传播的遗传决定因素。
