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Cell. 2018 Sep 6;174(6):1465-1476.e13. doi: 10.1016/j.cell.2018.07.031. Epub 2018 Aug 16.

Cell-Penetrating Peptide Mediates Intracellular Membrane Passage of Human Papillomavirus L2 Protein to Trigger Retrograde Trafficking.

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Department of Genetics, Yale School of Medicine, New Haven, CT 06520-8005, USA.
Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520-8002, USA.
Department of Genetics, Yale School of Medicine, New Haven, CT 06520-8005, USA; Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520-8040, USA; Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06520-8024, USA; Yale Cancer Center, New Haven, CT 06520-8028, USA. Electronic address:


Cell-penetrating peptides (CPPs) are short protein segments that can transport cargos into cells. Although CPPs are widely studied as potential drug delivery tools, their role in normal cell physiology is poorly understood. Early during infection, the L2 capsid protein of human papillomaviruses binds retromer, a cytoplasmic trafficking factor required for delivery of the incoming non-enveloped virus into the retrograde transport pathway. Here, we show that the C terminus of HPV L2 proteins contains a conserved cationic CPP that drives passage of a segment of the L2 protein through the endosomal membrane into the cytoplasm, where it binds retromer, thereby sorting the virus into the retrograde pathway for transport to the trans-Golgi network. These experiments define the cell-autonomous biological role of a CPP in its natural context and reveal how a luminal viral protein engages an essential cytoplasmic entry factor.


HIV Tat; HPV; cell-penetrating peptide; protein transduction domain; proximity ligation assay; retrograde; retromer; split GFP; virus

[Available on 2019-09-06]
[Indexed for MEDLINE]

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