Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Sep 25;5(10):2349-74.
doi: 10.3390/v5102349.

Evolution of foamy viruses: the most ancient of all retroviruses

Axel Rethwilm  1 , Jochen Bodem
Affiliations
Review

Evolution of foamy viruses: the most ancient of all retroviruses

Axel Rethwilm et al. Viruses. .

Abstract

Recent evidence indicates that foamy viruses (FVs) are the oldest retroviruses (RVs) that we know and coevolved with their hosts for several hundred million years. This coevolution may have contributed to the non-pathogenicity of FVs, an important factor in development of foamy viral vectors in gene therapy. However, various questions on the molecular evolution of FVs remain still unanswered. The analysis of the spectrum of animal species infected by exogenous FVs or harboring endogenous FV elements in their genome is pivotal. Furthermore, animal studies might reveal important issues, such as the identification of the FV in vivo target cells, which than require a detailed characterization, to resolve the molecular basis of the accuracy with which FVs copy their genome. The issues of the extent of FV viremia and of the nature of the virion genome (RNA vs. DNA) also need to be experimentally addressed.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The principal replication strategies of viruses making use of reverse transcription. While orthoretroviruses are RNA viruses, which replicate through a DNA intermediate and require integration for reproduction, hepadnaviruses are DNA viruses replicating through an RNA intermediate without the integration of their genome. FVs appear to functionally bridge these pathways, since they reverse transcribe (at least to a significant extent) late in replication (like hepadnaviruses) and must integrate their genome into the host cell genome (like orthoretroviruses). Furthermore, cellular exit of FV particles depends on their cognate glycoprotein as in hepadnaviruses, while budding of orthoretroviral particles is Env-independent (Figure adapted from [3]). RT, reverse transcriptase.
Figure 2
Figure 2
Prototype foamy virus (PFV) genome organization with particular reference to the length and structure of the long terminal repeat (LTR) with the canonical U3, R and U5 regions. The retroviral genes (gag, pro-pol, env) are abbreviated as usual. The FV accessory tas and orf-2 reading frames are shown, as well as the spliced reading frame, giving rise to the Bet protein. The start of transcription in the LTR is indicated by an arrow in the enlargement at the bottom. The numbers refer to lengths in kilobase pairs (kbp) or base pairs (bp).
Figure 3
Figure 3
Overall nucleotide genome conservation of primate lentiviral (A) and primate foamy viral (B) genomes. The values are approximate and show a reciprocal feature of lentiviral and foamy viral gag and env genes. For clarity, accessory reading frames have been omitted (adapted from [81]).
Figure 4
Figure 4
Phylogeny of current endogenous and exogenous FV pol amino acid sequences (from the active center-specifying integrase sequences and comprising 142 codons). A neighbor-joining tree was calculated by using the Maximum Composite Likelihood method with a bootstrap test of 10,000 replicates. BFV, bovine FV (NP_044929.1); EFV equine FV (NP_054716.1); PFV, prototypic FV (in red) (Y07725.1); SFVcpz, SFV from chimpanzee (CCP47057); SFVgor, SFV from gorilla (AY195688.1); SFVora, SFV from orangutan (CAD67562); SFVagm, African green monkey (Cercopithecus aethiops) FV (YP_001956722.2); SFVcha, SFV from Chlorocebus aethiops (CAM34599); SFVcep, SFV from Cercopithecus pygerythrus (AAV92627); SFVman, SFV from mandrill (ADO65890.1); SFVpap, SFV from Papio (CAM34655); SFVmcy (previously SFVmac) from Macaca mulatta, SFV from Macaca cyclopis (CAA41394.1); SFVtup, SFV from Tupaia [155] (AGN49359); SFVspm, SFV from spider monkey (ABV59399.1); SFVmar, SFV from marmosets (ADE06000.1); SFVsqu, SFV from squirrel monkeys (ADE05995.1); FFV, feline FV (NP_056914); Puma, FV from Puma concolor (AGC11913); RaFV-1, FV from the bat Rhinolophus affinis (AFK85015); SloEFV, endogenous FV from sloths (Katzourakis et al., 2009); CoeEFV, endogenous FV in the coelacanth (Latimeria) genome (JX006241.1); platyfish EFV, endogenous FV from platyfish (M. Schartl, personal communication); zebrafish EFV, zebrafish (M. Schartl, personal communication); and Cod EFV, codfish (M. Schartl, personal communication) genomes; integrase encoding sequences of the macaque simian immunodeficiency virus (SIVmac in magenta) (AAC57420.1) served as the outlier; the endogenous FV sequence from aye-aye (PSFVaye) [156] was not incorporated, because integrase sequences are not available.
Figure 5
Figure 5
A 425-nucleotide fragment from the conserved region of the integrase domain of pol was used to establish the phylogenetic tree demonstrating the phylogenetic relations of SFVcpz, PFV and SFVgor. The position of the proviral PFV (red) sequence and other proviral plasmids (blue) are indicated. SIVmac (magenta) served as an outlier. Pan paniscus is Bonobo.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Linial M.L. Foamy viruses are unconventional retroviruses. J. Virol. 1999;73:1747–1755. - PMC - PubMed
    1. Rethwilm A. Molecular biology of foamy viruses. Med. Microbiol. Immunol. 2010;199:197–207. doi: 10.1007/s00430-010-0158-x. - DOI - PubMed
    1. Rethwilm A., Lindemann D. Foamy Viruses. In: Knipe D.M., Howley P.M., editors. Fields Virology. 6th ed. Volume 6. Lippincott Williams & Wilkins; Philadelphia, PA, USA: 2013. pp. 1613–1632.
    1. Lindemann D., Rethwilm A. Foamy virus biology and its application for vector development. Viruses. 2011;3:561–585. doi: 10.3390/v3050561. - DOI - PMC - PubMed
    1. Rethwilm A. Foamy virus vectors: An awaited alternative to gammaretro- and lentiviral vectors. Curr. Gene Ther. 2007;7:261–271. doi: 10.2174/156652307781369092. - DOI - PubMed

LinkOut - more resources