Infectious Entry of Merkel Cell Polyomavirus.
A549 Cells
Antigens, Viral, Tumor
/ metabolism
Carcinoma, Merkel Cell
/ virology
Cell Line
Cell Line, Tumor
Cell Movement
/ physiology
Fibroblasts
/ virology
HEK293 Cells
HeLa Cells
Heparitin Sulfate
/ metabolism
Humans
Merkel cell polyomavirus
/ metabolism
N-Acetylneuraminic Acid
/ metabolism
Polyomavirus Infections
/ virology
Skin
/ virology
Skin Neoplasms
/ virology
Tumor Virus Infections
/ virology
Viral Tropism
/ physiology
MCPyV
endocytosis
polyomavirus
virus entry
virus-host interaction
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
15 03 2019
15 03 2019
Historique:
received:
08
11
2018
accepted:
23
12
2018
pubmed:
11
1
2019
medline:
20
11
2019
entrez:
11
1
2019
Statut:
epublish
Résumé
Merkel cell polyomavirus (MCPyV) is a small, nonenveloped tumor virus associated with an aggressive form of skin cancer, Merkel cell carcinoma (MCC). MCPyV infections are highly prevalent in the human population, with MCPyV virions being continuously shed from human skin. However, the precise host cell tropism(s) of MCPyV remains unclear: MCPyV is able to replicate within a subset of dermal fibroblasts, but MCPyV DNA has also been detected in a variety of other tissues. However, MCPyV appears different from other polyomaviruses, as it requires sulfated polysaccharides, such as heparan sulfates and/or chondroitin sulfates, for initial attachment. Like other polyomaviruses, MCPyV engages sialic acid as a (co)receptor. To explore the infectious entry process of MCPyV, we analyzed the cell biological determinants of MCPyV entry into A549 cells, a highly transducible lung carcinoma cell line, in comparison to well-studied simian virus 40 and a number of other viruses. Our results indicate that MCPyV enters cells via caveolar/lipid raft-mediated endocytosis but not macropinocytosis, clathrin-mediated endocytosis, or glycosphingolipid-enriched carriers. The viruses were internalized in small endocytic pits that led the virus to endosomes and from there to the endoplasmic reticulum (ER). Similar to other polyomaviruses, trafficking required microtubular transport, acidification of endosomes, and a functional redox environment. To our surprise, the virus was found to acquire a membrane envelope within endosomes, a phenomenon not reported for other viruses. Only minor amounts of viruses reached the ER, while the majority was retained in endosomal compartments, suggesting that endosome-to-ER trafficking is a bottleneck during infectious entry.
Identifiants
pubmed: 30626687
pii: JVI.02004-18
doi: 10.1128/JVI.02004-18
pmc: PMC6401430
pii:
doi:
Substances chimiques
Antigens, Viral, Tumor
0
Heparitin Sulfate
9050-30-0
N-Acetylneuraminic Acid
GZP2782OP0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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