Search

Foamy virus (FV) is a retrovirus with a safer integration profile than other retroviruses, rendering it appealing for gene therapy. Prototype FV (PFV) vector systems have been devised to yield high-titer vectors carrying large transgenes. Subsequent iterations of PFV vectors have been engineered to be replication-incompetent, enhancing their safety. A third generation PFV vector system, composed of four plasmids, has been adapted to accommodate large transgenes. Additionally, a novel dual-vector system shows promise for convenient and efficient gene delivery, particularly with the forthcoming development of stable producer cell lines expressing PFV Env. FVs exhibit a broad host spectrum due to the ubiquitous presence of the host factor, heparan sulfate (HS), on their surface. The receptor-binding domain (RBD) of FV Env proteins plays a crucial role in binding to the host cell HS. The FV vector system has been employed in hematopoietic stem cell (HSC) gene therapy to address monogenic diseases in dog and mouse models. In addition, FV vectors safely and efficiently deliver anti-HIV transgenes to HSCs, and vectors carrying HIV epitopes successfully induce antibodies against HIV, offering the promise of anti-HIV gene therapy and vaccine development. In this review, we delve into the development and utilization of FV vector systems, emphasizing their unique advantages in gene therapy, including their non-pathogenic nature, broad host tropism, large transgene capacity, and persistence in resting cells. Furthermore, we discuss the potential of FV vectors in tackling current challenges in gene therapy and their viability as valuable tools for treating genetic diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)