HIV1- identification of the specific restriction factor SAMHD1 Monsef Benkirane Institut de Génétique Humaine Montpellier CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD
Dendritic cells are refractory to HIV-1 infection Does HIV-1 escapes innate immune recognition by avoiding productive infection of Dendritic cells? X
> Initially isolated as an IFN -induced factor in macrophages and dendritic cells > Like for TREX1 and RNASEH2, mutations in SAMHD1 results in Aicardi Goutière Syndrome AGS AGS is a rare genetic disorder that mimics symptoms from a congenital infection AGS is associated with an increased production of IFN α Purification of Vpx-associated proteins SAM domain and HD domain 1 Protein-Protein interaction domain SAM HD Putative hydrolase domain 45 110 164 319 626 1 Missing in isoform 2 113-126
The big picture Would decreasing Samhd1 levels allow for better immune control of HIV-1 infection?
Conclusion and perspectives SAMHD1 is the dendritic and myeloid cells-specific HIV-1-restriction factor counteracted by Vpx <ul><li>Understanding SAMHD1 function </li></ul><ul><li>- What is the natural function of SAMHD1 in Macrophages and Dendritic cells? </li></ul><ul><li>What substrate for SAMHD1? </li></ul><ul><li>Why has HIV-1 not evolved means to counteract SAMHD1? </li></ul><ul><li>What is the involvement of SAMHD1 in the physiopathology of AIDS ? </li></ul><ul><ul><li>In non human primates </li></ul></ul><ul><ul><li>In HIV elite controllers, LTNPS </li></ul></ul><ul><li>Implication for Dendritic cell–based vaccine development. </li></ul>
Many thanks to: LAGUETTE Nadine CHABLE-BESSIA Christine SOBHIAN Bijan RINGEARD Mathieu YATIM Ahmad SCHWARTZ Olivier CASARTELLI Nicoletta EMILIANI Stéphane SEGERAL Emmanuel