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Site directed mutagenesis Y143C Q148H N155H G140S+Q148H

# 2970 Effects of HIV integrase polymorphisms on raltegravir -resistance susceptibility. H Suzuki 1 , M Maejima 2 , H Ode 2 , J Hattori 2 , M Nishizawa 1 , S Ibe 2 , Y Iwantani 2,3 , Y Yokomaku 2 , W Sugiura 1,2,3

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Site directed mutagenesis Y143C Q148H N155H G140S+Q148H

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  1. #2970 Effects of HIV integrase polymorphisms on raltegravir-resistance susceptibility H Suzuki1, M Maejima2, H Ode2, J Hattori2, M Nishizawa1, S Ibe2, Y Iwantani2,3, Y Yokomaku2, W Sugiura1,2,3 1.AIDS Research Center, National Institute of Infectious Diseases (NIID), Tokyo, Japan 2. Clinical Research Center, Nagoya Medical Center, Nagoya, Japan 3.Department of AIDS Research, Nagoya Graduate School of Medicine, Nagoya, Japan Background and Objective: Integrase is naturally polymorphic enzyme. Clarify the effect of IN polymorphisms on RAL-resistance and replication capacity. Methods: Construction of RAL resistant viruses Site directed mutagenesis Y143C Q148H N155H G140S+Q148H in house phenotyping & replication capacity evaluation env vpr LTR 5304 gag LTR pol 3932 vif rev tat tat nef vpu IN from Pt 864bp Not1 PflM1

  2. #2970 Effects of HIV integrase polymorphisms on raltegravir-resistance susceptibility HXB2 DR1093 DR7026 HXB2 DR1093 DR7026 1. Little effect of backbone IN polymorphisms in RAL resistance 2. Backbone In polymorphisms affected RC of RAL resistance clones Fold resistance Luciferase activity WT WT Y143C Y143C N155H N155H Q148H Q148H G140S/Q148H G140S/Q148H the results match with RAL vs. IN vs. Mg2+ affinities by homology modeling Pre-existing IN mutations affected RC significantly, whereas the effects to RAL resistance were limited. Our data suggest RC appeared to be more important in determining RAL resistance pathways.

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