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SRX8330765: GSM4548178: first run_D12_C6; Human immunodeficiency virus 1; OTHER
1 ILLUMINA (Illumina MiSeq) run: 12,661 spots, 6.4M bases, 4.1Mb downloads

Submitted by: NCBI (GEO)
Study: Complementation can maintain a quasispecies of drug sensitive and resistant HIV
show Abstracthide Abstract
The goal of this study was to determine how an HIV quasispecies is maintained in the face of selection. We deep sequenced the HIV provirus from cell populations as well as single cells at different time points from in vitro evolution experiments and found that when a less fit and more fit infect the same cell, they share components (complmentation) and therefore allow the less fit to perpetuate. We reproduced a quasispecies to an HIV reverse transcriptase inhibitor. The drug resistant genotype never completely supplanted the drug sensitive genotype, which stabilized at about 20% of viral sequences. Single-cell sequencing showed that resistant genotype frequency plateaued when cells were co-infected with sensitive and resistant genotypes, suggesting a sharing of viral proteins in co-infected cells (complementation), masking genotypic differences. To test if complementation can confer phenotypic drug resistance, we co-transfected fluorescently labelled molecular clones of sensitive and resistant HIV and observed drug resistance in genotypically sensitive virus from co-transfected cells. Resistant virus preferentially co-infected cells with drug sensitive HIV, explaining initiation of co-infections. Modelling showed that a stable quasispecies could form at the experimental multiplicities of infection. Conclusions: Complementation can lead to a quasispecies in infection environments where multiple infections per cell are common Overall design: Sequencing of Reverse transcriptase region of HIV proviral DNA from infected cell populations (3 independent experiments) as well as single cells (either 30 or 60 cells from each time point)
Sample: first run_D12_C6
SAMN14898788 • SRS6650172 • All experiments • All runs
Library:
Instrument: Illumina MiSeq
Strategy: OTHER
Source: GENOMIC
Selection: other
Layout: PAIRED
Construction protocol: For infected single cells, the cells were lysed and DNA was kept suspended in the lysis buffer. For infected cell populations, genomic DNA was extracted using the QIAamp DNA mini kit (Qiagen) Phusion hot start II DNA polymerase (New England Biolabs) PCR reaction mix (10$ul 5 x Phusion HF buffer, 1ul dNTPs, 2.5ul of the forward primer, 2.5ul of the reverse primer, 0.5ul Phusion hot start II DNA polymerase, 2.5ul of DMSO and molecular biology grade water to 50ul reaction volume) was added to the lysed single cells or extracted genomic DNA of cell populations. Two rounds of PCR were performed. The first-round reaction amplified a region of the RT gene in the proviral DNA using the forward primer 5' tcgtcggcagcgtcagatgtgtataagagacagTTAATAAGAGAACTCAAGATTTC 3' and reverse primer 5' gtctcgtgggctcggagatgtgtataagagacagCCCCACCTCAACAGATGTTGTC 3'. Non-capitalized portion of the primers represent the Nextera XT Index Kit adaptors. Cycling program was 98C for 30 seconds, then 35 cycles of 98C for 10 seconds, 50C for 30 seconds and 72C for 15 seconds with a final extension of 72C for 5 minutes. 1$\mu l$ of the first round product was then transferred into a PCR mix as above, with second round Nextera XT Index Kit adaptor primers (forward 5' tcgtcggcagcgtcagatgtgtataagagacag 3', reverse 5' gtctcgtgggctcggagatgtgtataagagacag 3'). The second round PCR amplified a 400bp product which was then visualized on a 1% agarose gel. The PCR amplicon was gel extracted using the QIAquick gel extraction kit (Qiagen). Illumina indices were attached to the amplicon with the Nextera XT Index Kit and deep sequenced using the Illumina Miseq. Fast-q files were analysed in Geneious. amplicon sequencing using illumina MiSeq with adaptors from Nextera kit
Experiment attributes:
GEO Accession: GSM4548178
Links:
Runs: 1 run, 12,661 spots, 6.4M bases, 4.1Mb
Run# of Spots# of BasesSizePublished
SRR1177783512,6616.4M4.1Mb2020-05-14

ID:
10836668

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