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Series GSE157511 Query DataSets for GSE157511
Status Public on Sep 05, 2020
Title HIV cell-to-cell spread slows evolution of drug resistance
Organism Homo sapiens
Experiment type Other
Summary Here we investigated whether a combination of cell-free infection and cell-to-cell spread confers a selective advantage in the evolution of resistance to an inhibitor relative to cell-to-cell spread alone due to the stronger selection pressure against drug sensitive virus.
We propagated HIV infection using coculture of infected with uninfected cells in the face of the reverse transcriptase inhibitor efavirenz (EFV), and compared the effect on drug resistance evolution of including one cycle of cell-free infection. In the presence of a single cell-free infection step, we obtained earlier evolution of resistance to EFV. When we increased selective pressure by adding emtricitabine (FTC as a second drug, infection with the cell-free step evolved multidrug resistance and was able to replicate, while infection without a cell-free step failed to evolve multidrug resistance.
In conclusion, our results suggest that, HIV cell-to-cell spread has a decreased capacity to rapidly evolve resistance to inhibitors, which is conferred by cell-free infection.
 
Overall design Mathenmatical modeling of evoltion of drug resistance by cell-free infection and cell-to-cell sread supported by sequencing of Reverse transciptase region of proviral DNA from infected cell populations over 48hr timepoints at 20nM EFV, 40nM EFV and a combination of 20nM EFV and 770nM FTC
E7 clone was generated by subcloning RevCEM cells at single cell density. Surviving clones were subdivided into replicate plates. One of the plates was screened for the fraction of GFP expressing cells upon HIV infection using microscopy, and the clone with the highest fraction of GFP positive cells was selected
 
Contributor(s) Hunter J, Cele S, Jackson L, Giandhari J, de Olivera T, Lustig G, Sigal A
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Submission date Sep 04, 2020
Last update date Sep 07, 2020
Contact name Alex Sigal
E-mail(s) Alex.Sigal@ahri.org
Phone +27312604917
Organization name Africa Health Research Institute
Lab Sigal Lab
Street address 719 Umbilo Road, K-RITH Tower building, Level 5
City Durban
State/province KwaZulu-Natal
ZIP/Postal code 4001
Country South Africa
 
Platforms (2)
GPL15520 Illumina MiSeq (Homo sapiens)
GPL17301 Ion Torrent PGM (Homo sapiens)
Samples (143)
GSM4768939 20nM EFV evolution experiment 1 [Day4]
GSM4768940 20nM EFV evolution experiment 1 [Day6CF]
GSM4768941 20nM EFV evolution experiment 1 [Day8CC]
Relations
BioProject PRJNA661547
SRA SRP280132

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Supplementary file Size Download File type/resource
GSE157511_RAW.tar 7.3 Mb (http)(custom) TAR (of CSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
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