Apr 23, 2020

Complementation can maintain a quasispecies of drug sensitive and resistant HIV

BioRxiv : the Preprint Server for Biology
L. JacksonAlex Sigal

Abstract

HIV exists as multiple genotypes in a single infected individual referred to as a quasispecies. Here we reproduced a quasispecies by moderate selective pressure using an HIV reverse transcriptase inhibitor. The drug resistant genotype never completely supplanted the drug sensitive genotype, which stabilized at about 20 percent 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) which masks 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 that genotypically sensitive virus from co-transfected cells was drug resistant. Resistant virus preferentially infected cells in tandem with drug sensitive HIV, explaining how co-infections of sensitive and resistant genotypes were initiated. Modelling this effect, we observed that a stable quasispecies could form at the experimental multiplicities of infection for the drug resistant and drug sensitive virus, showing that complementation can lead to a quasispecies in an...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Genome
Nucleic Acid Sequencing
Drosophila
Genomics
Sequencing
Sequence Determinations, DNA
Chromosomes
Psathyrella
Simulation
Drosophila

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.