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Evolution of foamy viruses: the most ancient of all retroviruses.

Rethwilm A, Bodem J - Viruses (2013)

Bottom Line: The analysis of the spectrum of animal species infected by exogenous FVs or harboring endogenous FV elements in their genome is pivotal.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.

View Article: PubMed Central - PubMed

Affiliation: Universität Würzburg, Institut für Virologie und Immunbiologie, Versbacher Str.7, Würzburg 97078, Germany. virologie@vim.uni-wuerzburg.de.

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.

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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.
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viruses-05-02349-f001: 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.

Mentions: Even hepadnaviruses, which are related to FVs in terms of their replication pathway (Figure 1), show a one thousand-fold higher in vivo point mutation rate upon chronic human infections [16], despite the fact that they have a much more compact genetic order with largely overlapping reading frames that puts constraints on the variability of hepadnaviruses [31]. Indeed, the common origin of retroviruses with hepadnaviruses has been suggested long ago [32,33], and FVs might represent this evolutionary link, from which both viral families evolved [34,35,36]. However, fossil viral records are not available to address this question. Thus, for the time being, the relation of FV genomes to orthoretroviruses and hepadnaviruses is more or less a functional one. Therefore, due to the accuracy of genome copying and sequence stability, an FV sequence can be used to determine the animal subspecies of its origin, provided the exclusion of trans-species infection [37]. This feature has practical consequences, for instance, by designing breeding strategies for non-human primates (NHPs). For obvious reasons, it is often impossible to obtain blood samples from wild or quasi-wild animals, particularly the great apes. However, methods have been adapted from experiences in AIDS-research to amplify FV sequences from fecal samples obtained without disturbing the animals [38]. Due to the enormous genome conservation of FVs, such analyses revealed a phylogenetic co-distribution of the viruses with their hosts [37].


Evolution of foamy viruses: the most ancient of all retroviruses.

Rethwilm A, Bodem J - Viruses (2013)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814592&req=5

viruses-05-02349-f001: 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.
Mentions: Even hepadnaviruses, which are related to FVs in terms of their replication pathway (Figure 1), show a one thousand-fold higher in vivo point mutation rate upon chronic human infections [16], despite the fact that they have a much more compact genetic order with largely overlapping reading frames that puts constraints on the variability of hepadnaviruses [31]. Indeed, the common origin of retroviruses with hepadnaviruses has been suggested long ago [32,33], and FVs might represent this evolutionary link, from which both viral families evolved [34,35,36]. However, fossil viral records are not available to address this question. Thus, for the time being, the relation of FV genomes to orthoretroviruses and hepadnaviruses is more or less a functional one. Therefore, due to the accuracy of genome copying and sequence stability, an FV sequence can be used to determine the animal subspecies of its origin, provided the exclusion of trans-species infection [37]. This feature has practical consequences, for instance, by designing breeding strategies for non-human primates (NHPs). For obvious reasons, it is often impossible to obtain blood samples from wild or quasi-wild animals, particularly the great apes. However, methods have been adapted from experiences in AIDS-research to amplify FV sequences from fecal samples obtained without disturbing the animals [38]. Due to the enormous genome conservation of FVs, such analyses revealed a phylogenetic co-distribution of the viruses with their hosts [37].

Bottom Line: The analysis of the spectrum of animal species infected by exogenous FVs or harboring endogenous FV elements in their genome is pivotal.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.

View Article: PubMed Central - PubMed

Affiliation: Universität Würzburg, Institut für Virologie und Immunbiologie, Versbacher Str.7, Würzburg 97078, Germany. virologie@vim.uni-wuerzburg.de.

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.

Show MeSH
Related in: MedlinePlus