Identification of a new 2-amino acid insertion in the integrase coding region of HIV-1 subtype G isolates

J Med Virol. 2021 Nov;93(11):6388-6392. doi: 10.1002/jmv.27205. Epub 2021 Jul 21.

Abstract

Amino acid insertions have been rarely found in the integrase (IN) coding region of Human immunodeficiency virus 1 (HIV-1), and have been considered as natural polymorphisms. It is still unclear the potential impact of these insertion mutations on the viral replication capacity and/or susceptibility to integrase strand transfer inhibitors (INSTIs). The objective of this study was to describe a previously unreported amino acid insertion in the IN coding region of HIV-1 isolates obtained from antiretroviral treatment-naïve infected individuals. Nucleotide sequences of HIV-1 isolates obtained from two infected individuals were analyzed for genotypic resistance to antiretroviral drugs. Phylogenetic inference was carried out for HIV-1 genetic variant identification. An unreported insertion of a threonine (T) and an asparagine (N) between codon 255 and 256 (S255N_TN) was identified in the IN C-terminal domain of HIV-1 subtype G isolates. No resistance-associated mutations to INSTIs were detected in the inserted sequences. Both individuals maintained undetectable HIV-1 RNA viral load, 24 months after undergoing antiretroviral treatment with an INSTI containing regimen. The results demonstrated the possibility of transmission of this insertion mutation and suggested that the codon 255 insert by itself may not affect susceptibility to INSTIs.

Keywords: HIV-1; insertion mutation; integrase; subtype G.

MeSH terms

  • Amino Acids / genetics*
  • Anti-Retroviral Agents / therapeutic use
  • Drug Resistance, Viral / genetics
  • Female
  • Frameshift Mutation*
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV Integrase / genetics*
  • HIV Integrase Inhibitors / pharmacology
  • HIV-1 / classification
  • HIV-1 / genetics*
  • Humans
  • Male
  • Mutation
  • Open Reading Frames / genetics*
  • Phylogeny
  • Sequence Analysis, DNA

Substances

  • Amino Acids
  • Anti-Retroviral Agents
  • HIV Integrase Inhibitors
  • HIV Integrase