The search result changed since you submitted your search request. Documents might be displayed in a different sort order.
  • search hit 1 of 2
Back to Result List

Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration

  • Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs) via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H) screen with prototype FV (PFV) Gag protein as bait we identified human polo-like kinase 2 (hPLK2), a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P) motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. TheUnlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs) via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H) screen with prototype FV (PFV) Gag protein as bait we identified human polo-like kinase 2 (hPLK2), a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P) motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt) particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells.show moreshow less

Export metadata

Additional Services

Search Google Scholar Statistics
Metadaten
Author details:Irena Zurnic, Sylvia Hütter, Ute Rzeha, Nicole Stanke, Juliane Reh, Erik Müllers, Martin V. Hamann, Tobias Kern, Gesche K. Gerresheim, Fabian Lindel, Erik Serrao, Paul Lesbats, Alan N. Engelman, Peter CherepanovORCiD, Dirk Lindemann
DOI:https://doi.org/10.1371/journal.ppat.1005860
ISSN:1553-7366
ISSN:1553-7374
Pubmed ID:https://pubmed.ncbi.nlm.nih.gov/27579920
Title of parent work (English):PLoS Pathogens
Publisher:PLoS
Place of publishing:San Fransisco
Publication type:Article
Language:English
Year of first publication:2016
Publication year:2016
Release date:2020/03/22
Volume:12
Number of pages:36
Funding institution:DIGS-BB fellowship; Deutsche Forschungsgemeinschaft [Li621/3-3, Li621/4-1, Li621/4-2, Li621/6-1]; US National Institutes of Health [R01 AI052014, P30 AI060354]
Organizational units:Zentrale und wissenschaftliche Einrichtungen / Potsdam Transfer - Zentrum für Gründung, Innovation, Wissens- und Technologietransfer
Peer review:Referiert
Accept ✔
This website uses technically necessary session cookies. By continuing to use the website, you agree to this. You can find our privacy policy here.