Direct Binding of Retromer to Human Papillomavirus Type 16 Minor Capsid Protein L2 Mediates Endosome Exit during Viral Infection

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The human papillomaviruses are important carcinogens, but little is known about how these non-enveloped viruses traffic to the nucleus, the site of genome replication. We use imaging, biochemical, and genetic techniques to show that a multi-subunit intracellular trafficking machine known as retromer binds directly to the L2 minor capsid protein in the virus particle to initiate its transport from the endosome to other membrane-bound organelles farther inside the cell. Most notably, knock-down of retromer expression or mutation of newly identified retromer binding sites in L2 cause the accumulation of incoming HPV16 capsids in the endosome and prevent trafficking to the Golgi. These defects can be corrected by insertion of a retromer binding site from a cellular cargo. Because all previously known retromer cargoes are cellular transmembrane proteins, the virus represents a new class of retromer cargo. In addition to elucidating the mechanism of viral endosome escape, these results suggest that retromer may play a more versatile role in cell biology than previously recognized.

Vyšlo v časopise: Direct Binding of Retromer to Human Papillomavirus Type 16 Minor Capsid Protein L2 Mediates Endosome Exit during Viral Infection. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004699
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004699

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