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Foamy Virus Protein — Nucleic Acid Interactions during Particle Morphogenesis

View Article: PubMed Central - PubMed

ABSTRACT

Compared with orthoretroviruses, our understanding of the molecular and cellular replication mechanism of foamy viruses (FVs), a subfamily of retroviruses, is less advanced. The FV replication cycle differs in several key aspects from orthoretroviruses, which leaves established retroviral models debatable for FVs. Here, we review the general aspect of the FV protein-nucleic acid interactions during virus morphogenesis. We provide a summary of the current knowledge of the FV genome structure and essential sequence motifs required for RNA encapsidation as well as Gag and Pol binding in combination with details about the Gag and Pol biosynthesis. This leads us to address open questions in FV RNA engagement, binding and packaging. Based on recent findings, we propose to shift the point of view from individual glycine-arginine-rich motifs having functions in RNA interactions towards envisioning the FV Gag C-terminus as a general RNA binding protein module. We encourage further investigating a potential new retroviral RNA packaging mechanism, which seems more complex in terms of the components that need to be gathered to form an infectious particle. Additional molecular insights into retroviral protein-nucleic acid interactions help us to develop safer, more specific and more efficient vectors in an era of booming genome engineering and gene therapy approaches.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of the foamy virus Gag and Pol protein organization. (a) Schematic illustration of the PFV Gag protein organization and selected functional motifs. Several functional motifs of PFV Gag are highlighted in differentially colored boxes. The organization of the C-terminal GR-rich region and the amino acid sequence of the PFV Gag protein are shown in the enlargement below. Numbers indicate amino acid positions of the PFV Gag protein. The black arrow marks the cleavage site of pr71Gag for processing into p68Gag and p3Gag. Gray boxes represent the historically annotated GR boxes (GR-I to -III) within the domain, which is now referred to as the GR-rich region. Arginine residues are highlighted in blue. CTRS: cytoplasmic targeting and retention signal; NES: nuclear export signal; CBS: chromatin binding signal; (NLS): originally annotated putative nuclear localization signal. (b) Schematic illustration of the PFV Pol protein organization. Numbers indicate amino acid positions of the PFV Pol protein. The black arrow marks the cleavage site of pr127Pol for processing into p85PR-RT and p40IN. PR: protease domain; L: linker sequence; RT: reverse transcriptase domain; RH: RNase H domain; IN: integrase domain. Panels (a) and (b) are adapted from [18].
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viruses-08-00243-f004: Schematic representation of the foamy virus Gag and Pol protein organization. (a) Schematic illustration of the PFV Gag protein organization and selected functional motifs. Several functional motifs of PFV Gag are highlighted in differentially colored boxes. The organization of the C-terminal GR-rich region and the amino acid sequence of the PFV Gag protein are shown in the enlargement below. Numbers indicate amino acid positions of the PFV Gag protein. The black arrow marks the cleavage site of pr71Gag for processing into p68Gag and p3Gag. Gray boxes represent the historically annotated GR boxes (GR-I to -III) within the domain, which is now referred to as the GR-rich region. Arginine residues are highlighted in blue. CTRS: cytoplasmic targeting and retention signal; NES: nuclear export signal; CBS: chromatin binding signal; (NLS): originally annotated putative nuclear localization signal. (b) Schematic illustration of the PFV Pol protein organization. Numbers indicate amino acid positions of the PFV Pol protein. The black arrow marks the cleavage site of pr127Pol for processing into p85PR-RT and p40IN. PR: protease domain; L: linker sequence; RT: reverse transcriptase domain; RH: RNase H domain; IN: integrase domain. Panels (a) and (b) are adapted from [18].

Mentions: The overall structure of FV Gag proteins is different though, which directly raises the question of how FVs package their vgRNA (Figure 4a) [48,49]. Originally, MA, CA and NC domains were designated to the FV Gag precursor, however, the post-translational maturation of FV Gag is very limited compared with orthoretroviral Gag proteins and results in an immature capsid morphology of FVs (Figure 1b) [50,51]. Thus, the orthoretroviral domain terminology is no longer applied to FV Gag proteins.


Foamy Virus Protein — Nucleic Acid Interactions during Particle Morphogenesis
Schematic representation of the foamy virus Gag and Pol protein organization. (a) Schematic illustration of the PFV Gag protein organization and selected functional motifs. Several functional motifs of PFV Gag are highlighted in differentially colored boxes. The organization of the C-terminal GR-rich region and the amino acid sequence of the PFV Gag protein are shown in the enlargement below. Numbers indicate amino acid positions of the PFV Gag protein. The black arrow marks the cleavage site of pr71Gag for processing into p68Gag and p3Gag. Gray boxes represent the historically annotated GR boxes (GR-I to -III) within the domain, which is now referred to as the GR-rich region. Arginine residues are highlighted in blue. CTRS: cytoplasmic targeting and retention signal; NES: nuclear export signal; CBS: chromatin binding signal; (NLS): originally annotated putative nuclear localization signal. (b) Schematic illustration of the PFV Pol protein organization. Numbers indicate amino acid positions of the PFV Pol protein. The black arrow marks the cleavage site of pr127Pol for processing into p85PR-RT and p40IN. PR: protease domain; L: linker sequence; RT: reverse transcriptase domain; RH: RNase H domain; IN: integrase domain. Panels (a) and (b) are adapted from [18].
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5035957&req=5

viruses-08-00243-f004: Schematic representation of the foamy virus Gag and Pol protein organization. (a) Schematic illustration of the PFV Gag protein organization and selected functional motifs. Several functional motifs of PFV Gag are highlighted in differentially colored boxes. The organization of the C-terminal GR-rich region and the amino acid sequence of the PFV Gag protein are shown in the enlargement below. Numbers indicate amino acid positions of the PFV Gag protein. The black arrow marks the cleavage site of pr71Gag for processing into p68Gag and p3Gag. Gray boxes represent the historically annotated GR boxes (GR-I to -III) within the domain, which is now referred to as the GR-rich region. Arginine residues are highlighted in blue. CTRS: cytoplasmic targeting and retention signal; NES: nuclear export signal; CBS: chromatin binding signal; (NLS): originally annotated putative nuclear localization signal. (b) Schematic illustration of the PFV Pol protein organization. Numbers indicate amino acid positions of the PFV Pol protein. The black arrow marks the cleavage site of pr127Pol for processing into p85PR-RT and p40IN. PR: protease domain; L: linker sequence; RT: reverse transcriptase domain; RH: RNase H domain; IN: integrase domain. Panels (a) and (b) are adapted from [18].
Mentions: The overall structure of FV Gag proteins is different though, which directly raises the question of how FVs package their vgRNA (Figure 4a) [48,49]. Originally, MA, CA and NC domains were designated to the FV Gag precursor, however, the post-translational maturation of FV Gag is very limited compared with orthoretroviral Gag proteins and results in an immature capsid morphology of FVs (Figure 1b) [50,51]. Thus, the orthoretroviral domain terminology is no longer applied to FV Gag proteins.

View Article: PubMed Central - PubMed

ABSTRACT

Compared with orthoretroviruses, our understanding of the molecular and cellular replication mechanism of foamy viruses (FVs), a subfamily of retroviruses, is less advanced. The FV replication cycle differs in several key aspects from orthoretroviruses, which leaves established retroviral models debatable for FVs. Here, we review the general aspect of the FV protein-nucleic acid interactions during virus morphogenesis. We provide a summary of the current knowledge of the FV genome structure and essential sequence motifs required for RNA encapsidation as well as Gag and Pol binding in combination with details about the Gag and Pol biosynthesis. This leads us to address open questions in FV RNA engagement, binding and packaging. Based on recent findings, we propose to shift the point of view from individual glycine-arginine-rich motifs having functions in RNA interactions towards envisioning the FV Gag C-terminus as a general RNA binding protein module. We encourage further investigating a potential new retroviral RNA packaging mechanism, which seems more complex in terms of the components that need to be gathered to form an infectious particle. Additional molecular insights into retroviral protein-nucleic acid interactions help us to develop safer, more specific and more efficient vectors in an era of booming genome engineering and gene therapy approaches.

No MeSH data available.


Related in: MedlinePlus