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Series GSE84865 Query DataSets for GSE84865
Status Public on Aug 31, 2017
Title Ebola virus glycoprotein variant with increased infectivity for human cells dominated the 2013-2016 outbreak
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The unprecedented magnitude of the 2013-2016 Makona Ebola virus (M-EBOV) epidemic likely resulted from multiple epidemiologic factors that set it apart from previous outbreaks. Nonetheless, genetic adaptations that distinguish M-EBOV from previous isolates may also have contributed to the scale of the epidemic. Of particular interest is a M-EBOV glycoprotein (GP) variant, GP-A82V, that was first detected at the inflection point of the 2013-2016 outbreak - when the number of cases increased exponentially - and which completely supplanted the earlier M-EBOV sequence. We found that, as compared with the earlier strain, GP-A82V increased the ability of M-EBOV to fuse with and infect cells of primate origin, including human blood dendritic cells, without altering innate immune signaling in target cells. Residue 82 is located at the NPC1-binding site on M-EBOV GP and the increased infectivity of GP-A82V was restricted to cells from species in which the NPC1 orthologue bears primate-defining residues at the critical interface. We utilized HIV-derived lentiviral vectors pseudotyped with founder and A82V containing M-EBOV GPs to explore the potential that this modification alters how human monocyte-derived dendritic cells (MDDCs) respond to EBOV GP stimulation.
Overall design We generated stocks of lentiviral vector bearing one the following three M-EBOV GPs: founder, A82V, and A82V/T230A. These viral stocks were used to challenge MDDCs from two healthy, anonymous human donors. Stimulated MDDCs were harvested at 1, 2, 4, and 6 hours after viral addition. Gene expression in M-EBOV GP challenged MDDCs was compared to a unstimulated control.
Contributor(s) Diehl WE, Kim K, McDonel P, Kucukural A, Garber M, Luban J
Citation(s) 27814506
Submission date Jul 26, 2016
Last update date May 15, 2019
Contact name Alper Kucukural
Phone 7743124493
Organization name UMass Medical School
Department Program in Molecular Medicine
Lab Biocore
Street address 364 Plantation Street
City Worcester
State/province MA
ZIP/Postal code 01605
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (26)
GSM2252655 F70_0hr
GSM2252656 F70_A82V_1hr
GSM2252657 F70_A82V_2hr
BioProject PRJNA335391
SRA SRP079916

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Supplementary file Size Download File type/resource
GSE84865_genes_expression_expected_count.tsv.gz 1.2 Mb (ftp)(http) TSV
GSE84865_genes_expression_tpm.tsv.gz 1.3 Mb (ftp)(http) TSV
GSE84865_isoforms_expression_expected_count.tsv.gz 2.1 Mb (ftp)(http) TSV
GSE84865_isoforms_expression_tpm.tsv.gz 2.0 Mb (ftp)(http) TSV
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