Variability of the conserved V3 loop tip motif in HIV-1 subtype B isolates collected from Brazilian and French patients

The diversity of the V3 loop tip motif sequences of HIV-1 subtype B was analyzed in patients from Botucatu (Brazil) and Montpellier (France). Overall, 37 tetrameric tip motifs were identified, 28 and 17 of them being recognized in Brazilian and French patients, respectively. The GPGR (P) motif was predominant in French but not in Brazilian patients (53.5% vs 31.0%), whereas the GWGR (W) motif was frequent in Brazilian patients (23.0%) and absent in French patients. Three tip motif groups were considered: P, W, and non-P non-W groups. The distribution of HIV-1 isolates into the three groups was significantly different between isolates from Botucatu and from Montpellier (P < 0.001). A higher proportion of CXCR4-using HIV-1 (X4 variants) was observed in the non-P non-W group as compared with the P group (37.5% vs 19.1%), and no X4 variant was identified in the W group (P < 0.001). The higher proportion of X4 variants in the non-P non-W group was essentially observed among the patients from Montpellier, who have been infected with HIV-1 for a longer period of time than those from Botucatu. Among patients from Montpellier, CD4+ cell counts were lower in patients belonging to the non-P non-W group than in those belonging to the P group (24 cells/µL vs 197 cells/µL; P = 0.005). Taken together, the results suggest that variability of the V3 loop tip motif may be related to HIV-1 coreceptor usage and to disease progression. However, as analyzed by a bioinformatic method, the substitution of the V3 loop tip motif of the subtype B consensus sequence with the different tip motifs identified in the present study was not sufficient to induce a change in HIV-1 coreceptor usage

KIR genes and their human leukocyte antigen ligands in the progression to cirrhosis in patients with chronic hepatitis C

Natural killer (NK) cells play pivotal roles in immune responses against infection with viruses, such as hepatitis C virus (HCV), and killer cell immunoglobulin-like receptors (KIRs) are related to the activation and inhibition of NK cells. The aim of this study was to investigate the possibility that KIR genes and their human leukocyte antigen (HLA) ligands influence progression to cirrhosis in patients infected with genotype 1 of HCV. A total of 145 Brazilian patients with confirmed chronic hepatitis C grouped from F0 to F4 according to fibrosis progression to cirrhosis were evaluated. Genotyping of KIR and HLA genes was performed by polymerase chain reaction with sequence-specific oligonucleotide probes. The HLA-C2 KIR ligand was more frequent in patients than in healthy controls (74.5% vs 64.3%, p = 0.04, odds ratio (OR) = 1.6, 95% confidence interval (Cl) = 1.03-2.52). Moreover, the HLA-C1C2 genotype was more frequent in patients with advanced fibrosis or cirrhosis (F3-F4 group) than in patients in the F0-F2 group (61.6% vs 44.7%, p = 0.06) and in the F4 group compared with the F0-F3 group (65.7% vs 46.7%, p = 0.05, OR = 2.19, 95% CI = 1.01-4.73). NK and KIR ligands may contribute to the development of liver damage in patients chronically infected by HCV. (C) 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier B.V. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq