Horizontal gene transfer from human host to HIV-1 reverse transcriptase confers drug resistance and partly compensates for replication deficits

Virology. 2014 May;456-457:310-8. doi: 10.1016/j.virol.2014.03.023. Epub 2014 Apr 25.

Abstract

We investigated the origin and the effect of insertion D67D-THGERDLGPA within HIV-1 RT from a patient failing antiviral therapy. The insertion developed within the context of pre-existing NRTI and NNRTI mutations (M41L, L210W, T215Y and N348I). Concurrently, the NRTI mutations T69I and V118I and the NNRTI mutations K103N and Y181C were detected for the first time. High-level drug resistance (fold-changes≥50) and a good replication capacity (87% of wild-type) were observed, significantly higher than for the previous virus without insertion. The insertion was very similar to a region within human chromosome 17 (31/34 nucleotide identity), and had already been detected independently in a Japanese HIV-1 isolate. These results suggest that a particular sequence within human chromosome 17 is prone to horizontal gene transfer into the HIV-1 RT finger subdomain. This insertion confers selective advantage to HIV-1 by its contribution to multi-drug resistance and restoration of impaired replication capacity.

Keywords: Antiretroviral therapy; HIV/AIDS; Insertion; Resistance; Reverse transcriptase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human
  • Drug Resistance, Viral*
  • Gene Transfer, Horizontal*
  • HIV Infections / virology
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • HIV-1 / physiology
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Phylogeny
  • Protein Conformation
  • RNA, Viral / genetics
  • Sequence Analysis, DNA
  • Sequence Homology
  • Virus Replication*

Substances

  • RNA, Viral
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase

Associated data

  • GENBANK/KJ438641
  • GENBANK/KJ438642
  • GENBANK/KJ438643
  • GENBANK/KJ438644
  • GENBANK/KJ438645
  • GENBANK/KJ438646