Feline foamy virus-mediated marker gene transfer: Identification of essential genetic elements and influence of truncated and chimeric proteins

Abstract

Retroviral vectors derived from foamy or spumaretroviruses are considered promising tools for targeted gene delivery and vaccination purposes. In order to fully exploit this potential, we identified essential cis-acting sequences on the feline foamy virus (FFV) genome by constructing and analyzing a series of FFV-based replication-deficient vector genomes. Cis-acting sequences essentially required for marker gene transfer were found to be localized at two sites on the FFV genome: (i) in the 5'-untranslated region and close to the gag ATG and (ii) in the central part of the pol gene. The presence of two cis-acting sequences and their relative location on the FFV genome are similar but not identical to the functionally corresponding elements described for simian and primate foamy viruses.

Construction and characterization of efficient, stable and safe replication-deficient foamy virus vectors

“…4,20 Here, we concentrate on the characterization of env-bel-deleted FFV vectors and those with an additional SIN deletion.…”

“…The env gene turned out to be dispensable for vector function, a characteristic similar to other studied FVs. 9,20 In order to optimize the vector function, we focus in the present study on the construction and characterization of FFV vectors deleted in env or in almost the whole env-bel genomic region. The bel genes (Figure 1a) encode the viral Bel1/Tas transactivator and Bet that counteracts APOBEC3-mediated host restriction.…”

Feline Foamy Virus-Based Vectors: Advantages of an Authentic Animal Model

“…The identification of essential cis-elements was performed using the RC FFV Bet-Gfp vector [60] or the RD env-bel-deleted ubi-lacZ vector [54]. These studies were guided in part by corresponding studies in PFV-based vectors and molecular biology studies on PFV and FFV, especially those related to genome packaging and Gag and Pol protein expression [14,28,61].…”

“…It was found that the intact 5'SD is required for the cytoplasmatic accumulation of FFV-based RNA vector genomes [54]. Similarly, deletion of the 3'-end of the 5'-untranslated FFV leader sequence was not compatible with vector function [60]. …”

Development of Foamy Virus Vectors for Gene Therapy for Neurological Disorders and Other Diseases

“…In addition to the prototypic PFV (Trobridge et al, 1998;Heinkelein et al, 1998;Trobridge et al, 2002;Schmidt et al, 1995;Nestler et al, 1997;Heinkelein et al, 2002), a variety of FV vectors have been developed, including simian foamy virus type 1 (SFV-1, macaque) (Wu et al, 1998;Park et al, 2002) and feline foamy virus (FFV) (Bastone et al, 2006;Bastone et al, 2007). A series of vectors and helper plasmids derived from SFV-1 have been constructed, and the minimum vector sequence required for efficient gene transduction has been established.…”