RRC ID 44622
Author Sánchez-Felipe L, Villar E, Muñoz-Barroso I.
Title Entry of Newcastle Disease Virus into the host cell: role of acidic pH and endocytosis.
Journal Biochim. Biophys. Acta
Abstract Most paramyxoviruses enter the cell by direct fusion of the viral envelope with the plasma membrane. Our previous studies have shown the colocalization of Newcastle Disease Virus (NDV) with the early endosome marker EEA1 and the inhibition of NDV fusion by the caveolin-phosphorylating drug phorbol 12-myristate 13-acetate (PMA) prompted us to propose that NDV enters the cells via endocytosis. Here we show that the virus-cell fusion and cell-cell fusion promoted by NDV-F are increased by about 30% after brief exposure to low pH in HeLa and ELL-0 cells but not in NDV receptor- deficient cell lines such as GM95 or Lec1. After a brief low-pH exposure, the percentage of NDV fusion at 29 °C was similar to that at 37 °C without acid-pH stimulation, meaning that acid pH would decrease the energetic barrier to enhance fusion. Furthermore, preincubation of cells with the protein kinase C inhibitor bisindolylmaleimide led to the inhibition of about 30% of NDV infectivity, suggesting that a population of virus enters cells through receptor-mediated endocytosis. Moreover, the involvement of the GTPase dynamin in NDV entry is shown as its specific inhibitor, dynasore, also impaired NDV fusion and infectivity. Optimal infection of the host cells was significantly affected by drugs that inhibit endosomal acidification such as concanamycin A, monensin and chloroquine. These results support our hypothesis that entry of NDV into ELL-0 and HeLa cells occurs through the plasma membrane as well as by dynamin- low pH- and receptor- dependent endocytosis.
Volume 1838(1 Pt B)
Pages 300-9
Published 2014-1
DOI 10.1016/j.bbamem.2013.08.008
PII S0005-2736(13)00285-X
PMID 23994097
MeSH Animals CHO Cells Cell Membrane / drug effects Cell Membrane / metabolism* Cell Membrane / virology Chloroquine / pharmacology Cricetulus Dynamins / antagonists & inhibitors Dynamins / metabolism* Endocytosis* Endosomes / drug effects Endosomes / metabolism HeLa Cells Host-Pathogen Interactions Humans Hydrazones / pharmacology Hydrogen-Ion Concentration Indoles / pharmacology Macrolides / pharmacology Maleimides / pharmacology Membrane Fusion / drug effects Monensin / pharmacology Newcastle disease virus / drug effects Newcastle disease virus / physiology* Protein Kinase C / antagonists & inhibitors Protein Kinase C / metabolism Receptors, Virus / antagonists & inhibitors Receptors, Virus / metabolism* Thermodynamics Virion / drug effects Virion / physiology* Virus Internalization / drug effects
IF 3.438
Times Cited 8
Human and Animal Cells