Foamy Virus Capsid Assembly Occurs at a Pericentriolar Region Through a Cytoplasmic Targeting/Retention Signal in Gag

Yu, Shuyuarn F.; Eastman, Scott W.; Linial, Maxine L.

doi:10.1111/j.1600-0854.2006.00448.x

Cited by 53 publications

(88 citation statements)

References 58 publications

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“…3 A and B) provides a clue as to why the mutant viral integration sites cluster around centromeres: As chromosomes approach centrosomes at the end of mitosis, the centromeric regions could come in closer contact with the viral nucleoprotein complexes. Binding of GAG to centrosomes is integral to intracellular trafficking and biogenesis of the spumavirus (34)(35)(36), and it would be of interest to identify the centrosomal receptor for spumaviral GAG.…”

Section: Discussionmentioning

confidence: 99%

Structural basis for spumavirus GAG tethering to chromatin

Lesbats

Serrao

Maskell

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The interactions between a retrovirus and host cell chromatin that underlie integration and provirus expression are poorly understood. The prototype foamy virus (PFV) structural protein GAG associates with chromosomes via a chromatin-binding sequence (CBS) located within its C-terminal region. Here, we show that the PFV CBS is essential and sufficient for a direct interaction with nucleosomes and present a crystal structure of the CBS bound to a mononucleosome. The CBS interacts with the histone octamer, engaging the H2A-H2B acidic patch in a manner similar to other acidic patch-binding proteins such as herpesvirus latency-associated nuclear antigen (LANA). Substitutions of the invariant arginine anchor residue in GAG result in global redistribution of PFV and macaque simian foamy virus (SFV mac ) integration sites toward centromeres, dampening the resulting proviral expression without affecting the overall efficiency of integration. Our findings underscore the importance of retroviral structural proteins for integration site selection and the avoidance of genomic junkyards.retrovirus | integration | nucleosome | chromatin-binding

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Section: Discussionmentioning

confidence: 99%

Structural basis for spumavirus GAG tethering to chromatin

Lesbats

Serrao

Maskell

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…MA proteins of retroviruses are implicated in localization of assembly to membranes or to the microtubule organizing complex (74,82,85,103). Particle formation is dependent on the carboxyl-terminal domain (CTD) of CA and spacer and the I domain of NC, with contributions from different domains dominating in different viruses (1,23,32,73,95,96,99; reviewed in references 3, 64, 82, 98, and 100).…”

mentioning

confidence: 99%

Ty3 Capsid Mutations Reveal Early and Late Functions of the Amino-Terminal Domain

Larsen

Zhang

Beliakova-Bethell

et al. 2007

J Virol

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The Ty3 retrotransposon assembles into 50-nm virus-like particles that occur in large intracellular clusters in the case of wild-type (wt) Ty3. Within these particles, maturation of the Gag3 and Gag3-Pol3 polyproteins by Ty3 protease produces the structural proteins capsid (CA), spacer, and nucleocapsid. Secondary and tertiary structure predictions showed that, like retroviral CA, Ty3 CA contains a large amount of helical structure arranged in amino-terminal and carboxyl-terminal bundles. Twenty-six mutants in which alanines were substituted for native residues were used to study CA subdomain functions. Transposition was measured, and particle morphogenesis and localization were characterized by analysis of protein processing, cDNA production, genomic RNA protection, and sedimentation and by fluorescence and electron microscopy. These measures defined five groups of mutants. Proteins from each group could be sedimented in a large complex. Mutations in the amino-terminal domain reduced the formation of fluorescent Ty3 protein foci. In at least one major homology region mutant, Ty3 protein concentrated in foci but no wt clusters of particles were observed. One mutation in the carboxyl-terminal domain shifted assembly from spherical particles to long filaments. Two mutants formed foci separate from P bodies, the proposed sites of assembly, and formed defective particles. P-body association was therefore found to be not necessary for assembly but correlated with the production of functional particles. One mutation in the amino terminus blocked transposition after cDNA synthesis. Our data suggest that Ty3 proteins are concentrated first, assembly associated with P bodies occurs, and particle morphogenesis concludes with a post-reverse transcription, CA-dependent step. Particle formation was generally resistant to localized substitutions, possibly indicating that multiple domains are involved.

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“…All protein samples were mixed with 2ϫPPPC prior to separation by SDS-PAGE using 7.5% polyacrylamide gels. Immunoblotting using polyclonal antisera specific for PFV Gag (44), PFV IN (942054), simian foamy virus type 1 (SFV-1) PR-RT (67C6), and PFV Env leader peptide (Env-LP) (35), as well as hybridoma supernatants specific for PFV Gag (clone SGG-1) (36), PFV PR-RT (clone 15E10) or PFV IN (clone 3E11) (45), PFV Env surface unit (Env-SU) (clone P3E10) (46,47), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (G8795; Sigma) was performed as previously described (35). The chemiluminescence signal was digitally recorded using an LAS-3000 imager and quantified using ImageGauge in the linear range of the sample signal intensities as described previously (44).…”

Section: Methodsmentioning

confidence: 99%

Prototype Foamy Virus Protease Activity Is Essential for Intraparticle Reverse Transcription Initiation but Not Absolutely Required for Uncoating upon Host Cell Entry

Hütter

Müllers

Stanke

et al. 2013

J Virol

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bFoamy viruses (FVs) are unique among retroviruses in performing genome reverse transcription (RTr) late in replication, resulting in an infectious DNA genome, and also in their unusual Pol biosynthesis and encapsidation strategy. In addition, FVs display only very limited Gag and Pol processing by the viral protease (PR) during particle morphogenesis and disassembly, both thought to be crucial for viral infectivity. Here, we report the generation of functional prototype FV (PFV) particles from mature or partially processed viral capsid and enzymatic proteins with infectivity levels of up to 20% of the wild type. Analysis of protein and nucleic acid composition, as well as infectivity, of virions generated from different Gag and Pol combinations (including both expression-optimized and authentic PFV open reading frames [ORFs]) revealed that precursor processing of Gag, but not Pol, during particle assembly is essential for production of infectious virions. Surprisingly, when processed Gag (instead of Gag precursor) was provided together with PR-deficient Pol precursor during virus production, infectious, viral DNA-containing particles were obtained, even when different vector or proviral expression systems were used. Although virion infectivity was reduced to 0.5 to 2% relative to that of the respective parental constructs, this finding overturns the current dogma in the FV literature that viral PR activity is absolutely essential at some point during target cell entry. Furthermore, it demonstrates that viral PR-mediated Gag precursor processing during particle assembly initiates intraparticle RTr. Finally, it shows that reverse transcriptase (RT) and integrase are enzymatically active in the Pol precursor within the viral capsid, thus enabling productive host cell infection.

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Foamy Virus Capsid Assembly Occurs at a Pericentriolar Region Through a Cytoplasmic Targeting/Retention Signal in Gag

Cited by 53 publications

References 58 publications

Structural basis for spumavirus GAG tethering to chromatin

Structural basis for spumavirus GAG tethering to chromatin

Ty3 Capsid Mutations Reveal Early and Late Functions of the Amino-Terminal Domain

Prototype Foamy Virus Protease Activity Is Essential for Intraparticle Reverse Transcription Initiation but Not Absolutely Required for Uncoating upon Host Cell Entry

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