Real-time PCR quantitation of subtype C HIV DNA in a Zambian discordant couple cohort

AIDS Res Hum Retroviruses. 2006 May;22(5):438-44. doi: 10.1089/aid.2006.22.438.

Abstract

To study the viral sequence diversity that is characteristic of HIV infection, PCR amplification and sequencing of viral genes is an essential step. However, a limitation of traditional PCR methods is that one viral target may be preferentially amplified over another when multiple sequences are present. This presents a particular problem when conclusions about diversity are made from one or only a few PCRs. One way to avoid resampling is to perform a large number of PCR amplifications on a single template; however, this requires that extensive dilution series be carried out on each patient sample to identify the appropriate concentration of input DNA. Here we describe the development and implementation of a quantitative real-time PCR (qPCR) method that detects a short sequence in gag and is optimized to detect subtype C HIV sequences. The standard curve was externally validated using two chronically infected cell lines carrying a known number of HIV copies per genome, and this assay yielded reproducible and accurate measurements on patient DNA samples over a wide range of input targets. The qPCR assay results were consistent with those obtained by the traditional limiting dilution method yet entailed only a fraction of the time and reagents required for the latter. This robust and quantitative real-time assay can be used to ensure that each viral sequence obtained through PCR represents a single template for studies in which the diversity of the entire population must be accurately portrayed, and can readily be applied to other research settings and viral subtypes.

Publication types

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

MeSH terms

  • Cohort Studies
  • DNA, Viral / analysis*
  • Female
  • Genes, gag*
  • HIV Infections / virology*
  • HIV Seronegativity
  • HIV Seropositivity
  • HIV-1 / classification
  • HIV-1 / genetics*
  • Humans
  • Male
  • Polymerase Chain Reaction / methods*
  • Reference Standards
  • Reproducibility of Results
  • Sexual Partners
  • Zambia / epidemiology

Substances

  • DNA, Viral