The Determination of HIV-1 RT Mutation Rate, Its Possible Allosteric Effects, and Its Implications on Drug Resistance

Viruses. 2020 Mar 9;12(3):297. doi: 10.3390/v12030297.

Abstract

The high mutation rate of the human immunodeficiency virus type 1 (HIV-1) plays a major role in treatment resistance, from the development of vaccines to therapeutic drugs. In addressing the crux of the issue, various attempts to estimate the mutation rate of HIV-1 resulted in a large range of 10-5-10-3 errors/bp/cycle due to the use of different types of investigation methods. In this review, we discuss the different assay methods, their findings on the mutation rates of HIV-1 and how the locations of mutations can be further analyzed for their allosteric effects to allow for new inhibitor designs. Given that HIV is one of the fastest mutating viruses, it serves as a good model for the comprehensive study of viral mutations that can give rise to a more horizontal understanding towards overall viral drug resistance as well as emerging viral diseases.

Keywords: HIV-1; allostery; drug resistance; mutation rate; retroviruses; reverse transcriptase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allosteric Site / genetics*
  • Anti-HIV Agents / pharmacology
  • Drug Design
  • Drug Resistance, Viral / drug effects
  • Drug Resistance, Viral / genetics*
  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / drug effects
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / genetics*
  • Humans
  • Models, Molecular
  • Mutation
  • Mutation Rate*
  • Reverse Transcriptase Inhibitors / pharmacology

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase