Integrase (IN) is an essential enzyme in retroviral life cycle. It mediates viral cDNA integration into host cellular DNA. Feline foamy virus (FFV) is a member of the Spumavirus subfamily of Retroviridae. Recently, its life cycle has been proposed to be different from other retroviruses. Despite this important finding, FFV IN is not understood clearly. Here, we constructed point mutations in FFV IN C-terminal domain (CTD) to obtain a clear understanding of its integration mechanism. Mutation of the amino acid residues in FFV IN CTD interacting with target DNA reduced both IN enzymatic activities in vitro and viral productions in infected cells. Especially, the mutants, R307 and K340, made viral DNA integration less efficient and allowed accumulation of more unintegrated viral DNA, thereby suppressing viral replication. Therefore, we suggest that the CTD residues interacting with the target DNA play a significant role in viral DNA integration and replication.

整合酶（IN）是逆转录病毒生命周期中必不可少的酶。它介导病毒cDNA整合入宿主细胞DNA。猫泡沫病毒（FFV）是逆转录病毒科的Spumavirus亚科的成员。最近，有人提出其生命周期不同于其他逆转录病毒。尽管有这一重要发现，但对FFV IN的了解仍不清楚。在这里，我们构建了FFV IN C端域（CTD）中的点突变，以对其整合机制有一个清晰的了解。FFV IN CTD中的氨基酸残基突变与靶DNA相互作用降低了两种IN的体外酶活性和被感染细胞中的病毒产生。特别是，突变体R307和K340使病毒DNA整合效率降低，并允许积累更多未整合的病毒DNA，从而抑制了病毒复制。因此，我们建议与目标DNA相互作用的CTD残基在病毒DNA整合和复制中起重要作用。