Phylogenetic analysis of HIV-1 Gag cleavage sites polymorphism in HIV acutely infected patients Castro E 1,2, Cavassini M 1, Bart PA 2 and Pantaleo G 2.

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Presentation transcript:

Phylogenetic analysis of HIV-1 Gag cleavage sites polymorphism in HIV acutely infected patients Castro E 1,2, Cavassini M 1, Bart PA 2 and Pantaleo G 2. 1 Service of Infectious Diseases and 2 Laboratory of AIDS Immunopathogenesis, Service of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois and Lausanne University, Switzerland.

Baseline demographics and HIV infection related parameters of subjects from the study. Parameters (n=20) Age, mean years (range) 37.1 (25-53) Gender Men 19 (95.0) Women 1 (5.0) CD4+T cell count, median cells/mm 3 (IQR) 396 ( ) Log 10 HIV RNA, median copies/mL (IQR) 6.8 ( ) HLA locus B alleles B*07, B*57 or B*58 5 (25.0) Other B alleles 15 (75.0) Transmission route MSM 11 (55.0) Heterosexual 7 (35.0) Intravenous drug users 2 (10.0) Note Data are no. (%) of each parameter, unless otherwise indicated. IQR, iterquartile range.

Laboratory workflow Schematic representation of HIV-1 gene map and related Gag cleavage site substrates.

HIV-1 clade assignment based on phylogenetic analysis of gag and baseline genotypic reassessment *. HIV-1 clade of the 20 isolates studiedSubtypesRecombinant forms B (10) CRF02_AG (3) F1 (3) CRF11_like (2) CRF01_AE (1) 13 isolates 7 isolates Drug resistance related mutations Resistance mutations and clades Protease polymorphisms and clades RT K103N (3F1) G16E (3F1,1CRF01_AE) Prot L10V (3F1,1B) K20I (3CRF02_AG) D60E (3F1,2CRF11_like) I62V (1B) 4 isolates 10 isolates * Castro E et al.: HIV-1 drug resistance transmission networks in southwest Switzerland. AIDS Res Hum Retroviruses ; 26: Note: Data are no. of each parameter. CRF refers to HIV-1 circulating recombinant forms.

p17 p24 p2/p7/p1 /p6 Gag p24-p7 amino acid alignment from a subset of sequences from the study. Patient Clade HLA-B * Patient Clade HLA-B * HXB2 Reference Sequence: gag relative position GPGHKARVLA EAMSQVTNSA TIMMQRGNFR NQRKIVKCFN CGKEGHTARN CRAPRK GPGHKARVLA EAMSQVTNSA TIMMQRGNFR NQRKIVKCFN CGKEGHTARN CRAPRK 07/40 PHI-5 CRF01 07/40..S AQ-NV N K G.K-RI L CRF02 08/14..S AQ-Q. NV G..-TI.... WA.RD--TPE IAR.LG 11 CRF11 37/ Q-HT N..I..S..K G..-RI.... WA.KD--TPE IAG.LX 14 CRF02 08/18..S AQ-Q. NV G..-TI L....K CRF11 35/ Q-PT N..I G.K-RI L F1 08/ A.-TT K.L..NS..K G..R TD--TPQ /57 6 B 18/57..S A...H.....G.K.K I B 08/14..S AN-QT.....K.... K.G WAERD--TP. IAG.LG 9 B 07/13..S AN-QT.....K.... K.G WAERD--TP. IAG.LG 10 B 35/51..S T. NV...K..V.....PI.... WA.K.--TPE IAG.PG 12 B 15/ V S WA.K.--TQE IAG.LG 13 B 44/ M...T A....K.... S...T..... WA.K.--TPE IAG.LG GPGHKARVL Gag-p24 CTL epitope Gag-p2 encoding region Zinc finger binding region LARNCRAPRK Gag-p7 CTL epitope

HIV-1 Gag motifs replacing CD8 T-cell epitope lengths in B and non-B clades. Natural polymorphisms at key target sites of future maturation inhibitors. Protease inhibitors drug resistance related polymorphisms mostly concerning wild type non-B clades. Conclusions

. Thank you for your attention.