Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Schelhaas, M; Shah, B; Holzer, M; Blattmann, P; Kühling, L; Day, PM; Schiller, JT; Helenius, A.
Entry of human papillomavirus type 16 by actin-dependent, clathrin- and lipid raft-independent endocytosis.
PLoS Pathog. 2012; 8(4):e1002657-e1002657
Doi: 10.1371/journal.ppat.1002657
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- Co-authors Med Uni Graz
- Holzer Michael
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- Abstract:
- Infectious endocytosis of incoming human papillomavirus type 16 (HPV-16), the main etiological agent of cervical cancer, is poorly characterized in terms of cellular requirements and pathways. Conflicting reports attribute HPV-16 entry to clathrin-dependent and -independent mechanisms. To comprehensively describe the cell biological features of HPV-16 entry into human epithelial cells, we compared HPV-16 pseudovirion (PsV) infection in the context of cell perturbations (drug inhibition, siRNA silencing, overexpression of dominant mutants) to five other viruses (influenza A virus, Semliki Forest virus, simian virus 40, vesicular stomatitis virus, and vaccinia virus) with defined endocytic requirements. Our analysis included infection data, i.e. GFP expression after plasmid delivery by HPV-16 PsV, and endocytosis assays in combination with electron, immunofluorescence, and video microscopy. The results indicated that HPV-16 entry into HeLa and HaCaT cells was clathrin-, caveolin-, cholesterol- and dynamin-independent. The virus made use of a potentially novel ligand-induced endocytic pathway related to macropinocytosis. This pathway was distinct from classical macropinocytosis in regards to vesicle size, cholesterol-sensitivity, and GTPase requirements, but similar in respect to the need for tyrosine kinase signaling, actin dynamics, Na⁺/H⁺ exchangers, PAK-1 and PKC. After internalization the virus was transported to late endosomes and/or endolysosomes, and activated through exposure to low pH.
- Find related publications in this database (using NLM MeSH Indexing)
- Actins - metabolism
- Caveolins - metabolism
- Clathrin - metabolism
- Endocytosis -
- HeLa Cells -
- Human papillomavirus 16 - physiology
- Humans -
- Membrane Microdomains - metabolism
- Papillomavirus Infections - genetics
- Protein Kinase C - metabolism
- Signal Transduction -
- Sodium-Hydrogen Antiporter - metabolism
- Virus Internalization -
- p21-Activated Kinases - metabolism