Analysis of Recombination in the HIV-1pol Gene

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Analysis of Recombination in the HIV-1pol Gene
Richard Myers Division of Infection and
Immunity University College London
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HIV-1 Recombination

• HIV-1 sequence classification 3 groups (M, N
  and O) and 9 subtypes (A-H, J and K).
• Recombination by superinfection / co-infection.
• There are 16 HIV-1 CRFs most common CRF01 (AE)
  and CRF02 (AG).
• Intra-subtype recombination exists, but is harder
  to detect and studied less extensively.

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Detecting Recombination in pol
Seq Data 10,545 HIV pol Sequences
STAR
Rec-PSSM
Subtypes
Inter-subtypes
Rec-Triplet (all data/pure subtypes)
Intra-subtypes
History analysis for each recombinant
by Phylogenetic Trees etc
Non-Recombinant Subtypes
LOHA
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STAR

• High throughput subtyping tool that uses Position
  Specific Scoring Matrices (PSSMs).
• Myers, R. E., Clarke, C., Khan, A., Kellam, P.,
  Tedder, R. (2006). Genotyping Hepatitis B Virus
  from whole and sub-genomic fragments using
  position specific scoring matrices in STAR-HBV.
  J. Gen Virol. (In Press).
• Myers, R. E., Gale, C. V., Harrison, A.,
  Takeuchi, Y. Kellam, P. (2005). A statistical
  model for HIV-1 sequence classification using the
  subtype analyser (STAR). Bioinformatics 21,
  3535-40.
• Gale, C. V., Myers, R., Tedder, R. S., Williams,
  I. G. Kellam, P. (2004). Development of a novel
  human immunodeficiency virus type 1 subtyping
  tool, Subtype Analyzer (STAR) analysis of
  subtype distribution in London. AIDS Res Hum
  Retroviruses 20, 457-64.
• http//www.vgb.ucl.ac.uk/starn.shtml

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Subtyping Concordance
10545 sequences from the UK National Resistance
Database
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STAR and Rec-PSSM Results
Subtype Frequency n.10545
Distribution of Recombinant Architectures
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CRF 03
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CRF 04
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Detection of CRFs
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Conclusions

• Large number of HIV-1 non-B subtypes in the UK
  (32.6).
• The UK epidemic contains HIV-1 subtype
  recombinants (11).
• Evidence for recombination outside of established
  CRFs.
• Only 10 of recombinant sequences appear to be
  established CRFs (excluding CRF01/02
• General mixing of HIV-1 sequences and breakdown
  of subtype classification.

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HIV-1 Subtype Evolution?
Rambaut et al 2005 Nature Reviews Genetics
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Acknowledgements
Paul Kellam Yasu Takeuchi Catherine Gale Robert
Gifford Arshad Kahn
MRC / UCL Centre for Medical Molecular Virology
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Detecting Recombination in pol

• Detecting Recombination in HIV-1 pol is a 3 step
  process.
• 1. Separate pure subtype sequences from
  putative recombinant sequences (Subtype Analyser
  STAR, Rec-PSSM).
• 2. Analyse putative recombinant sequences using a
  high throughput screen for inter-subtype
  recombination (Rec-PSSM).
• 3. Analyse pure subtype sequences for
  intra-subtype recombination (Triplet-Rec).

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STAR and Rec-PSSM Results
Subtype Frequency n.10545
Distribution of Recombinant Architectures