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Foamy Virus Assembly with Emphasis on Pol Encapsidation

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Lee, Eun-Gyung, Stenbak, Carolyn, Linial, Maxine·2013·Viruses
DOI 10.3390/v5030886PMC PMC3705302
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Abstract

Foamy viruses (FVs) differ from all other genera of retroviruses (orthoretroviruses) in many aspects of viral replication. In this review, we discuss FV assembly, with special emphasis on Pol incorporation. FV assembly takes place intracellularly, near the pericentriolar region, at a site similar to that used by betaretroviruses. The regions of Gag, Pol and genomic RNA required for viral assembly are described. In contrast to orthoretroviral Pol, which is synthesized as a Gag-Pol fusion protein and packaged through Gag-Gag interactions, FV Pol is synthesized from a spliced mRNA lacking all Gag sequences. Thus, encapsidation of FV Pol requires a different mechanism. We detail how WT Pol lacking Gag sequences is incorporated into virus particles. In addition, a mutant in which Pol is expressed as an orthoretroviral-like Gag-Pol fusion protein is discussed. We also discuss temporal regulation of the protease, reverse transcriptase and integrase activities of WT FV Pol.

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Figure 1 Genome of prototype foamy virus (PFV). Depicted is the molecular clone PFV-13 (GenBank accession no. U21247; 11,954 bases). The shaded boxes below the genome indicate the location of the LTR promoter regions in the proviral DNA. (A) The thin lines represent the genomic RNA and mRNA for Pol protein. Pol is expressed from a spliced mRNA. The 5´ splice site (ss) and the 3´ splice site (3´ss) are indicated. (B) The colored boxes indicate the three major PFV protein products: Gag, Pol and Env. PR-mediated cleavage sites are indicated with dashed lines and arrows. CTRS, cytoplasmic targeting and retention signal; GR boxes, glycine/arginine-rich motifs; PR, protease; RT, reverse transcriptase; IN, integrase. LP, leader peptide; SU, surface domain; TM, transmembrane domain. (C) The thick lines represent RNA sequences required for proper assembly. Cis-acting sequences (CAS) are required for genomic RNA packaging; Pol encapsidation sequences (PES) are required for Pol packaging.
Figure 1 Genome of prototype foamy virus (PFV). Depicted is the molecular clone PFV-13 (GenBank accession no. U21247; 11,954 bases). The shaded boxes below the genome indicate the location of the LTR promoter regions in the proviral DNA. (A) The thin lines represent the genomic RNA and mRNA for Pol protein. Pol is expressed from a spliced mRNA. The 5´ splice site (ss) and the 3´ splice site (3´ss) are indicated. (B) The colored boxes indicate the three major PFV protein products: Gag, Pol and Env. PR-mediated cleavage sites are indicated with dashed lines and arrows. CTRS, cytoplasmic targeting and retention signal; GR boxes, glycine/arginine-rich motifs; PR, protease; RT, reverse transcriptase; IN, integrase. LP, leader peptide; SU, surface domain; TM, transmembrane domain. (C) The thick lines represent RNA sequences required for proper assembly. Cis-acting sequences (CAS) are required for genomic RNA packaging; Pol encapsidation sequences (PES) are required for Pol packaging.CC BY · PubMed Central
Figure 2 Model of regulation of Pol enzymatic activities during virus assembly. (A) The precursor Pol protein contains the protease (PR), reverse transcriptase (RT) and integrase (IN) domains. (B) Upon incorporation into virions, the precursor Pol protein forms dimers through IN-IN interactions. (C) The dimerization of precursor Pol allows formation of the PR active site. (D) Active PR cleaves Gag and Pol proteins, as indicated by the dashed lines. (E) After cleavage, PR-RT remains a monomer and is active as a polymerase, initiating reverse transcription of the viral RNA genome. Free IN is also active.
Figure 2 Model of regulation of Pol enzymatic activities during virus assembly. (A) The precursor Pol protein contains the protease (PR), reverse transcriptase (RT) and integrase (IN) domains. (B) Upon incorporation into virions, the precursor Pol protein forms dimers through IN-IN interactions. (C) The dimerization of precursor Pol allows formation of the PR active site. (D) Active PR cleaves Gag and Pol proteins, as indicated by the dashed lines. (E) After cleavage, PR-RT remains a monomer and is active as a polymerase, initiating reverse transcription of the viral RNA genome. Free IN is also active.CC BY · PubMed Central

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Metadata

Authors
Lee, E.-G., Stenbak, C., & Linial, M.
Affiliations
  • Fred Hutch Cancer Center (US)
  • Seattle University (US)
Corresponding author
Linial, Maxine
Venue
Viruses
Publisher
MDPI AG
Published
2013-03-20
Volume
5
Issue
3
Pages
886-900
ISSN
1999-4915 (ISSN-L)
DOI
10.3390/v5030886
PMC
PMC3705302
OpenAlex
W1983893496
Cited by
15
References
1
Citations by year
2025: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2019: 2 · 2017: 1 · 2016: 2 · 2014: 1 · 2013: 3
FWCI
0.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Viruses (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Pfizer
  • National Institutes of Health
  • National Cancer Institute (R01 CA18282, R01CA018282)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Mycology
Keywords
foamy virus, viral assembly, spliced mRNA, proteolytic activity, reverse transcriptase activity, retroviral replication
MeSH terms
Animals, Capsid, Humans, Retroviridae Infections, Gene Products, pol, Gene Expression Regulation, Viral, Spumavirus, Virus Assembly

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