Tropism Testing Who needs a Phenotype Arevir Meeting May 2011 Swiss - - PowerPoint PPT Presentation

tropism testing who needs a phenotype arevir meeting may
SMART_READER_LITE
LIVE PREVIEW

Tropism Testing Who needs a Phenotype Arevir Meeting May 2011 Swiss - - PowerPoint PPT Presentation

Tropism Testing Who needs a Phenotype Arevir Meeting May 2011 Swiss 3 step System Element 1 (TrackC): (ca. 85% of analyses) Element 2 (Geno2Pheno): -RNA-DNA conversion (cDNA); (ca. 25% of analyses) -PCR-amplification of V3 region


slide-1
SLIDE 1

Tropism Testing – Who needs a Phenotype…

Arevir Meeting May 2011

slide-2
SLIDE 2
slide-3
SLIDE 3
slide-4
SLIDE 4

Swiss 3‐step System

Element 1 (TrackC): (ca. 85% of analyses)

  • RNA-DNA conversion (cDNA);
  • PCR-amplification of V3 region by PCR;
  • Hybridization to known DNA probes;
  • Capillary-based nucleic acid duplex tracking

assay “TrackC”: Element 2 (Geno2Pheno): (ca. 25% of analyses)

  • RNA-DNA conversion;
  • DNA-amplification of V3 region by PCR;
  • Sequencing of the env V3-region of the

viral genome;

  • Sequence based interpretation of V3

Amino Acid information using Geno2Pheno

slide-5
SLIDE 5

Element 3 (PhenX-R): (ca. 10% of analyses)

  • RNA-DNA conversion; amplification of env;
  • Cloning into replicative HIV cassette (plasmid lacking env);
  • Transfection into permissive human cell line;
  • 4-days virus replication in presence of drug;
  • Read-out: HIV tropism; virus fitness; dualtrop/mixes
slide-6
SLIDE 6

Viral RNA from Patient

Provirus-Cassette for the Env Gene (=> complete Virus!)

RT

Treatment in vitro w/ Corec.-Antagonists

RT

Env Env Env Env Env

Amplification

Env Env

“PhenX-R”

slide-7
SLIDE 7

Replicative phenotypic Tropism test

  • Why?

– To verify ambiguous Geno‐results – To assess minority populations – To discriminate dualtropic and mixed viruses – To determine viral fitness

slide-8
SLIDE 8
slide-9
SLIDE 9

rPhenotypic Tropism Testing

  • When?

– When FPR does not allow conclusive decision – Disagreement between TrackC/G2P – For unusual V3 lengths