Abstract
New-generation retroviral vectors have potential applications in vaccination and gene therapy. Foamy viruses are particularly interesting as vectors, because they are not associated to any disease. Vector research is mainly based on primate foamy viruses (PFV), but cats are an alternative animal model, due to their smaller size and the existence of a cognate feline foamy virus (FFV). The potential of replication-competent (RC) FFV vectors for vaccination and replication-deficient (RD) FFV-based vectors for gene delivery purposes has been studied over the past years. In this review, the key achievements and functional evaluation of the existing vectors from in vitro cell culture systems to out-bred cats will be described. The data presented here demonstrate the broad application spectrum of FFV-based vectors, especially in pathogen-specific prophylactic and therapeutic vaccination using RD vectors in cats and in classical gene delivery. In the cat-based system, FFV-based vectors provide an advantageous platform to evaluate and optimize the applicability, efficacy and safety of foamy virus (FV) vectors, especially the understudied aspect of FV cell and organ tropism.
Highlights
The use of viral vectors in clinical therapy is an emerging field
Dogs suffering from canine leukocyte adhesion deficiency were treated with a recombinant foamy viruses (FVs) expressing CD18 [2]
The feline calicivirus (FCV) E1 sequence with a length of 106 aa displayed reasonable genetic stability in the feline foamy virus (FFV) background and was selected as insert. Since it was not clear whether an intact long terminal repeat (LTR) is required for vector replication and gene expression, replicating FFV-FCV vectors with a U3 containing a partially deleted LTR (Figure 1c) and an intact LTR (Figure 1d) were analyzed in cats
Summary
The use of viral vectors in clinical therapy is an emerging field. In addition to the established methods of generating viral vaccines from attenuated or inactivated virus or viral derivatives, viruses, especially retroviruses, can be used as a vector for gene-mediated therapy. There is no reliable and/or fully or at least partially permissive small animal model for PFV replication, very low levels of replication may be detectable in PFV-infected mice and SFV-infected hamster [12,13] This necessitates the use of primates for functional studies of PFV-based replicating vectors for vaccination purposes. The isolate used as backbone for the current PFV vectors is the end-product of the zoonotic transmission of a chimpanzee SFV to humans [8,14,15,16] This single PFV isolate had suffered substantial deletions in the viral long terminal repeat (LTR) sequences, and the PFV Bet protein appears less functional in protecting the virus against host-mediated APOBEC3 restriction than its FFV counterpart [17,18,19,20]. FFV-based vectors (as summarized in Figure 1 and Tables 1 and 2)
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