Chemistry and Bioinformatics Considerations in Using Next-Generation Sequencing Technologies to Inferring HIV Proviral DNA Genome-Intactness

Viruses. 2021 Sep 19;13(9):1874. doi: 10.3390/v13091874.

Abstract

HIV persists via integration of the viral DNA into the human genome. The HIV DNA pool within an infected individual is a complex population that comprises both intact and defective viral genomes, each with a distinct integration site, in addition to a unique repertoire of viral quasi-species. Obtaining an accurate profile of the viral DNA pool is critical to understanding viral persistence and resolving interhost differences. Recent advances in next-generation deep sequencing (NGS) technologies have enabled the development of two sequencing assays to capture viral near-full- genome sequences at single molecule resolution (FLIP-seq) or to co-capture full-length viral genome sequences in conjunction with its associated viral integration site (MIP-seq). This commentary aims to provide an overview on both FLIP-seq and MIP-seq, discuss their strengths and limitations, and outline specific chemistry and bioinformatics concerns when using these assays to study HIV persistence.

Keywords: HIV genomes; HIV persistence; deep sequencing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Computational Biology
  • DNA, Viral / genetics
  • Genome, Human
  • Genome, Viral*
  • HIV Infections / virology*
  • HIV-1 / genetics*
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Proviruses / genetics*
  • Sequence Analysis, DNA
  • Virus Integration*

Substances

  • DNA, Viral