Scientists have used a genome sequencer system to monitor low frequency human immunodeficiency virus (HIV) variants from human samples.

Correct determination of HIV tropism is critical for the administration of a new class of drugs called CCR5 antagonists used for the treatment of AIDS. HIV tropism refers to the type of cell the HIV virus infects, as determined by coreceptors that the virus employs for entry into the cell. Determining the coreceptor that a HIV strain uses, CCR5, CXCR4, or a combination of both, is a critical component of monitoring and treating HIV.

454 Life Sciences (Branford, CT, USA), a Roche company (Indianapolis, IN, USA) announced that a team of scientists from the British Columbia (BC) Center of Excellence in HIV/AIDS (Vancouver, Canada) and the University of British Columbia, (Vancouver, Canada) used the company's genome sequencer FLX system in a recent study of HIV tropism. The 454 sequencing system has simple, unbiased sample preparation and long, highly accurate sequence reads, including paired-end reads. The technology of the sequencing system has enabled hundreds of studies in diverse fields including cancer, infectious diseases, and drug discovery

Preliminary results of the study found that conventional genotyping methods lack sufficient sensitivity for detection of the CXCR4 variant, which is a contraindication for administering CCR5 antagonists. By using deep sequencing, the team was able to quantify low-frequency variants associated with poor response to CCR5 antagonists and accurately determine HIV tropism across all individuals' samples.

The 454 sequencing system has a simple, unbiased sample preparation and long, highly accurate sequence reads, including paired-end reads. The technology of the sequencing system has enabled hundreds of studies in diverse fields including cancer, infectious diseases, and drug discovery

Preliminarily results of the study were presented by Dr. Richard Harrigan (lab director at the BC Center for Excellence in HIV/AIDS) at the HIV DART (Duke University AIDS Research and Treatment Center) conference in Puerto Rico on December 10, 2008. Dr. Harrigan explained, "The sensitivity of the genome sequencer FLX platform allowed us to monitor HIV sequence variation from 48 or 96 individuals´ samples simultaneously, and still have far greater ability to spot minority variants than using standard approaches."

He added that this has important implications for therapy monitoring. "The fact that the genome sequencer FLX system gives a quantitative measure of sequence variance within a sample is a bonus.”

The genome sequencer FLX system, powered by 454 sequencing, enables discoveries in de novo sequencing, resequencing of whole genomes and target DNA regions, metagenomics, and RNA analysis. Featuring a unique combination of long reads, exceptional accuracy, and ultra-high throughput, the genome sequencer FLX system delivers a comprehensive result at a low total cost, giving it excellent value for any next-generation sequencing platform.

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454 Life Sciences
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British Columbia Center of Excellence in HIV/AIDS