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Analysis of Recombination in the HIV-1 pol Gene

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

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Analysis of Recombination in the HIV-1 pol Gene

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

  2. 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.

  3. 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

  4. 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

  5. Subtyping Concordance 10545 sequences from the UK National Resistance Database

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

  7. CRF 03

  8. CRF 04

  9. Detection of CRF’s

  10. 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 CRF’s (excluding CRF01/02 • General mixing of HIV-1 sequences and breakdown of subtype classification.

  11. HIV-1 Subtype Evolution? Rambaut et al 2005; Nature Reviews Genetics

  12. Acknowledgements Paul Kellam Yasu Takeuchi Catherine Gale Robert Gifford Arshad Kahn MRC / UCL Centre for Medical Molecular Virology

  13. 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).

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

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