RESUMEN
In order to investigate the association between length variation of the CD209L neck region and human immunodeficiency virus (HIV)-1 susceptibility, disease progression, and treatment response outcomes, we genotyped 139 HIV-1-seropositive and 109 seronegative individuals. The heterozygous genotype 6/5 showed a significant increased risk of HIV-1 infection (OR 3.03, 95% CI 0.99-9.33, p 0.046). Moreover, after highly active antiretroviral therapy (HAART), HIV-1-seropositive individuals carrying the 6/5, 7/5 and 7/7 genotypes and alleles 5, 6 and 7 showed good CD4(+) T-cell recovery. In addition, individuals with the 7/5, 6/6 and 7/7 genotypes showed a significant decrease in viral load during the treatment period as compared with baseline (p < 0.05). Interestingly, we found that alleles 4 and 6 were associated with protection against AIDS progression. D209L variation may influence susceptibility to HIV-1, response to treatment, and disease progression.
Asunto(s)
Moléculas de Adhesión Celular/genética , Predisposición Genética a la Enfermedad , Infecciones por VIH/genética , VIH-1/aislamiento & purificación , Lectinas Tipo C/genética , Polimorfismo Genético , Receptores de Superficie Celular/genética , Secuencias Repetidas en Tándem , Adulto , Anciano , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Estudios de Cohortes , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Genotipo , Técnicas de Genotipaje , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Marruecos , Resultado del Tratamiento , Carga ViralRESUMEN
L-SIGN is a C-type lectin expressed on liver sinusoidal endothelial cells involved in the capture of hepatitis C virus and trans-infection of adjacent hepatocyte cells. The neck region of L-SIGN is highly polymorphic, with three to nine tandem repeats of 23 residues. This polymorphism is associated with a number of infectious diseases, but has not been explored in HCV. We therefore investigated the impact of L-SIGN neck region length variation on the outcome of HCV infection. We studied 322 subjects, 150 patients with persistent HCV infection, 63 individuals with spontaneous clearance and 109 healthy controls. In healthy subjects, we found a total of nine genotypes, with the 7/7 genotype being the most frequent (33%) followed by the 7/6 (22.9%) and the 7/5 (18.3%). The frequencies of the alleles were as follows: 7-LSIGN (56.4%), 6-LSIGN (20.2%), 5-L-SIGN (18.3%) and 4-L-SIGN (5%). The frequency of the 7/4 genotype was higher in spontaneous resolvers (14.3%) as compared with the persistent group (4%) (OR = 0.25, 95% CI = 0.07-0.82, p 0.022). In addition, we found that 4-L-SIGN was associated with spontaneous resolution of HCV infection (OR = 0.30, 95%CI, 0.12-0.74, p 0.005). Interestingly, patients with 4-L-SIGN had lower viral loads when compared with carriers of the 5 (p 0.001), 6 (p 0.021) and 7-alleles (p 0.048). The results indicate that neck region polymorphism of L-SIGN can influence the outcome of HCV infection and the four-tandem repeat is associated with clearance of HCV infection.
Asunto(s)
Moléculas de Adhesión Celular/genética , Frecuencia de los Genes , Hepatitis C Crónica/genética , Lectinas Tipo C/genética , Ganglios Linfáticos , Receptores de Superficie Celular/genética , Carga Viral , Anciano , Femenino , Genotipo , Hepacivirus , Humanos , Hígado , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite , Marruecos , Polimorfismo Genético , Remisión EspontáneaRESUMEN
The cytidine deaminase apolipoprotein B mRNA editing catalytic subunit-3 (APOBEC3) induces G-to-A hypermutation in hepatitis B virus (HBV) genomes and operates as part of the innate antiviral immune system. We investigated the associations between the presence of APOBEC3 variants and HBV carriage in a case-control study in the Moroccan population. A polymorphic deletion affecting the APOBEC3B gene and the H186R variant of APOBEC3G were genotyped in 179 HBV chronic carriers and 216 healthy control subjects. In addition, to assess the overall impact of APOBEC3 deaminases on circulating HBV, we looked for hyperedited forms of the viral genome using the 3DPCR technique and analysed editing context. Data analysis showed that there was no significant difference in the frequencies of deleted APOBEC3B alleles (P = 0.261) or genotypes (P = 0.333) between patients with chronic hepatitis B and control subjects. By contrast, subjects bearing deleted genotype had a faster progression of liver disease than those with the insertion genotype (adjusted OR, 3.72; 95% CI, 0.38-36.12). The analysis of the APOBEC3G H186R polymorphism revealed that R/R genotype frequencies were not significantly different in HBV infected patients and in healthy subjects. 3DPCR was positive in 26 samples (14%) among 179. Amplified viral segments displayed monomorphic G>A transitions highly reminiscent of APOBEC3G activity. Most intriguingly, hemi/homozygous carriers of the APOBEC3B deletion had significantly lower virus loads than patients with the wild type (median 539 vs. 2213 IU/mL, P = 0.0023). This result suggests that genetic variations in APOBEC3 cytidine deaminases do not predispose to chronicity but may modulate the course of persistent HBV infection.
Asunto(s)
Portador Sano/inmunología , Citidina Desaminasa/genética , Hepatitis B Crónica/genética , Hepatitis B Crónica/inmunología , Polimorfismo Genético , Desaminasa APOBEC-3G , Adulto , Anciano , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Hepatitis B Crónica/patología , Humanos , Masculino , Persona de Mediana Edad , Antígenos de Histocompatibilidad Menor , MarruecosRESUMEN
Human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are major public health concerns. We aimed to determine the prevalence of HBV and HCV infections among HIV-infected patients, and to identify the main circulating hepatitis strains in Morocco. The study was carried out in 503 HIV-infected patients. Our survey indicated that the prevalence of HIV/hepatitis co-infection was 10.6%; 5.2% of patients were HBV surface antigen positive, and 5.4% of patients were anti-HCV positive. Among the HBV surface antigen-positive group, HBV DNA sequencing identified exclusively genotype D (D1: 26.7%; D7: 73.3%) in accordance with what is found in the general population. In contrast, sequencing of HCV isolates produced an unusual subtype distribution with a decreasing order of prevalence: 1a, 3a (both 23.5%), 1b, 4a (both 17.6%), 1c (11.8%) and 6h (6%).
Asunto(s)
Coinfección/epidemiología , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Adulto , Coinfección/virología , Femenino , Hepatitis B/virología , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Marruecos/epidemiologíaRESUMEN
The molecular pathogenesis of hepatocellular carcinoma, a tumour characterized by a vast clinical heterogeneity, remains unexplored outside Europe and Eastern Asia. We analysed by direct sequencing or loss of heterozygosity assay, the common targets of genomic alterations in 42 hepatocellular carcinomas collected in western North-Africa. Overall, genomic instability was uncommon, allelic losses affecting mostly chromosomes 1p, 4q, 8p and 17p (24-28% of cases). CTNNB1 and TP53 were infrequently mutated (9 and 17% of cases, respectively). Surprisingly, TP53 mutation R249S, diagnostic of aflatoxin B1 exposure, usually frequent in Africa, was exceptional (one case), indicating that in western North-Africa, hepatocellular carcinoma genetics differs markedly from that of the remainder of the continent.