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Jan van Lunzen

Analysis of TRIM5α mRNA Polymorphisms and Characterization of a novel TRIM5α variant found in HIV-1 Long-Term Non-Progressors. Jan van Lunzen Heinrich-Pette-Institute for Experimental Virology and Immunology University Medical Center Hamburg Eppendorf. The Monkey Block.

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Jan van Lunzen

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  1. Analysis of TRIM5α mRNA Polymorphisms and Characterization of a novel TRIM5α variant found in HIV-1 Long-Term Non-Progressors Jan van Lunzen Heinrich-Pette-Institute for Experimental Virology and Immunology University Medical Center Hamburg Eppendorf

  2. The Monkey Block

  3. TRIM5alpha – Restriction Mechanism

  4. TRIM5alpha domain structure 43 174 693 1479 283 381 391 883 RING B-box2 coiled coil SPRY RBCC

  5. HIV disease progression

  6. Study subjects

  7. Polymorphisms in Rhesus monkeys 43 174 693 1479 283 381 391 883 RING B-box2 coiled coil SPRY RBCC

  8. 0 0 0 0 0 0 0 0 0 0 RING RING B-box2 B-box2 coiled coil coiled coil SPRY SPRY Distribution in Rhesus Monkeys LTNP Progressors

  9. 43 174 693 1479 Polymorphisms in human study subjects 283 381 391 883 RING B-box2 coiled coil SPRY RBCC

  10. Polymorphisms in human study subjects 43 174 693 1479 283 381 391 883 RING B-box2 coiled coil SPRY RBCC

  11. 0 RING RING RING B-box2 B-box2 B-box2 coiled coil coiled coil coiled coil SPRY SPRY SPRY 0 0 0 LTNP 226 389 1255 477 746 809 407 767Δ 940Δ 0 0 0 Progressors 226 389 809 1255 477 746 767Δ 407 940Δ 0 0 Seronegative 226 389 809 1255 477 746 940Δ 767Δ 407

  12. Functional analysis TRIM5alpha IRES-dTomato sF91-TRIM5alpha-dTom sF91-TRIM5alpha-dTom variants HIV NL43env-IRES-eGFP sort TRIM5alpha expressing cells Cf1Th and HeLa FACS

  13. Functional analysis

  14. Conclusions • Relatively high frequency of TRIM5α polymorhisms in humans and rhesus monkeys • No difference between LTNP and progressors in SIV infected rhesus macaques • Exchange aa R136Q more frequent in human LTNP compared to progressors • New 100 bp deletion overrepresented in human LTNP leading to shift of ORF • No major influence of this deletion on HIV infectivity in a functional in vitro assay

  15. Acknowledgements Heinrich-Pette-Institute for Experimental Virology and Immunology Joachim Hauber Philip Hartjen Nele Jensen Sebastian Frerk German Primate Center Christiane Stahl-Hennig

  16. Thank you!

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