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Assembly and Purification of Prototype Foamy Virus Intasomes
Published on: March 19, 2018
Prototype foamy virus gag nuclear localization: a novel pathway among retroviruses
Erik Müllers1, Kristin Stirnnagel, Sylvia Kaulfuss
1Institut für Virologie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
Journal of Virology
|July 1, 2011
Summary
Foamy virus (FV) Gag protein localizes to the nucleus during mitosis by binding to chromatin, not through a typical nuclear localization signal (NLS). This chromatin tethering mechanism is essential for Gag nuclear entry in foamy virus infections.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Nuclear localization of Gag protein is a key feature of foamy virus (FV) infection.
- Previously identified motifs, a chromatin-binding site (CBS) and a nuclear localization signal (NLS) in glycine-arginine-rich box II (GRII), were thought to mediate nuclear import.
- The precise mechanisms governing Gag nuclear translocation remain largely unelucidated.
Purpose of the Study:
- To investigate the nuclear localization mechanisms of prototype foamy virus (PFV) Gag.
- To characterize the nuclear import route of Gag, including the roles of the CBS and NLS.
- To determine if PFV Gag utilizes a canonical NLS-mediated pathway for nuclear entry.
Main Methods:
- Live-cell fluorescence microscopy was employed to monitor PFV Gag nuclear localization in real-time.
- Mutant PFV Gag proteins, including those tagged with a simian vacuolating virus 40-NLS (SV40-NLS), were analyzed.
- The contributions of the CBS and NLS to nuclear localization were dissected.
Main Results:
- PFV Gag does not enter the nucleus of interphase cells via NLS-mediated import and lacks a functional NLS.
- Nuclear localization of PFV Gag occurs exclusively through tethering to chromatin during mitosis.
- The CBS is critical for this chromatin-dependent nuclear localization, while the NLS is dispensable.
- Gag's nuclear localization is independent of other viral components like Pol, Env, and viral RNA.
- Adding a heterologous SV40-NLS enabled interphase nuclear import but did not restore infectivity in a Gag mutant.
Conclusions:
- PFV Gag nuclear localization utilizes a novel pathway distinct from typical NLS-mediated import, relying on chromatin tethering during mitosis.
- The chromatin-binding site (CBS) is essential for this unique nuclear entry mechanism.
- This novel pathway is not essential for viral infectivity or Pol encapsidation, suggesting specialized roles for Gag nuclear localization in FV biology.
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