RESUMEN
BACKGROUND: The time of progression towards AIDS can vary greatly among seropositive patients, and may be associated with host genetic variation. The NR1I2 (PXR) gene, a ligand-activated transcription factor, regulates the transcription immune pathway genes and can therefore be targets of viral replication mechanisms influencing time of progression to AIDS. OBJECTIVE: To verify the association of single nucleotide polymorphisms (SNPs) rs3814057, rs6785049, rs7643645, and rs2461817 in the NR1I2 (PXR) gene with progression to AIDS in HIV-1 infected patients. METHODS: Blood samples were obtained from 96 HIV-1 positive individuals following informed consent. DNA was isolated and genotyped through real time polymerase chain reaction (PCR) for the presence of SNPs in the NR1I2. Questionnaires on socio-demographic features and behaviors were answered and time of progression to AIDS was estimated based on medical chart analysis. FINDINGS: Patients with the GG genotype for rs7643645 were shown to be related with a more rapid disease progression when compared to GA and AA genotypes. This result was maintained by the Multivariate Cox Regression considering sex, ethnicity, and presence of HLA-B*57, HLA-B*27, and CCR5del32 polymorphisms. MAIN CONCLUSIONS: Recent studies reported the expression of the nuclear receptors in T-Lymphocytes, suggesting their possible role in the immune response. In addition, nuclear receptors have been shown to inhibit the HIV replication, although no such mechanism has been thoroughly elucidated to date. This is the first time an association between NR1I2 polymorphism and time of progression to AIDS is reported and supports an apparent relationship between the gene in the immune response and identifies another genetic factor influencing AIDS progression.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/genética , Progresión de la Enfermedad , Receptores de Esteroides/genética , Síndrome de Inmunodeficiencia Adquirida/patología , Adulto , Femenino , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Receptor X de PregnanoRESUMEN
Typical human immunodeficiency virus-1 subtype B (HIV-1B) sequences present a GPGR signature at the tip of the variable region 3 (V3) loop; however, unusual motifs harbouring a GWGR signature have also been isolated. Although epidemiological studies have detected this variant in approximately 17-50% of the total infections in Brazil, the prevalence of B"-GWGR in the southernmost region of Brazil is not yet clear. This study aimed to investigate the C2-V3 molecular diversity of the HIV-1B epidemic in southernmost Brazil. HIV-1 seropositive patients were ana-lysed at two distinct time points in the state of Rio Grande do Sul (RS98 and RS08) and at one time point in the state of Santa Catarina (SC08). Phylogenetic analysis classified 46 individuals in the RS98 group as HIV-1B and their molecular signatures were as follows: 26% B"-GWGR, 54% B-GPGR and 20% other motifs. In the RS08 group, HIV-1B was present in 32 samples: 22% B"-GWGR, 59% B-GPGR and 19% other motifs. In the SC08 group, 32 HIV-1B samples were found: 28% B"-GWGR, 59% B-GPGR and 13% other motifs. No association could be established between the HIV-1B V3 signatures and exposure categories in the HIV-1B epidemic in RS. However, B-GPGR seemed to be related to heterosexual individuals in the SC08 group. Our results suggest that the established B"-GWGR epidemics in both cities have similar patterns, which is likely due to their geographical proximity and cultural relationship.
Asunto(s)
Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Seropositividad para VIH/virología , VIH-1/aislamiento & purificación , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Brasil/epidemiología , Consumidores de Drogas/estadística & datos numéricos , Femenino , VIH-1/clasificación , VIH-1/genética , Heterosexualidad , Homosexualidad Masculina , Humanos , Masculino , Epidemiología Molecular , Filogenia , Prevalencia , Alineación de Secuencia/estadística & datos numéricos , Parejas Sexuales , Reacción a la TransfusiónRESUMEN
HPV types 16 and 18 were studied in paraffin-fixed cervical biopsy collected in southern Brazil. HPV 16, HPV 18 and co-infection HPV 16/18 were identified in 10/57 (17.5%), 4/57 (7%) and in 43/57 (75.4%) samples, respectively. Southern Brazil has one of the highest prevalence rates of HPV 16/18 reported.
Asunto(s)
Cuello del Útero/patología , Coinfección/virología , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Infecciones por Papillomavirus/virología , Adolescente , Adulto , Biopsia , Brasil/epidemiología , Cuello del Útero/virología , Coinfección/epidemiología , Coinfección/patología , Femenino , Papillomavirus Humano 16/clasificación , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/clasificación , Papillomavirus Humano 18/genética , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/patología , Prevalencia , Adulto JovenRESUMEN
Bone marrow stromal cell antigen-2 (BST-2)/Tetherin is a restriction factor that prevents Human immunodeficiency virus type 1 (HIV-1) release from infected cells and mediates pro-inflammatory cytokine production. This study investigated the risk conferred by single nucleotide polymorphisms (rs919266, rs9192677, and rs9576) at BST-2 coding gene (BST2) in HIV-1 mother-to-child transmission and in disease progression. Initially, 101 HIV-1+ pregnant women and 331 neonates exposed to HIV-1 from Zambia were enrolled. Additional BST2 single nucleotide polymorphism analyses were performed in 2 cohorts with acquired immunodeficiency syndrome (AIDS) progression: an adult Brazilian cohort (37 rapid, 30 chronic and 21 long-term non-progressors) and an Italian pediatric cohort (21 rapid and 67 slow progressors). The rs9576A allele was nominally associated with protection during breastfeeding (P = 0.019) and individuals carrying rs919266 GA showed slower progression to AIDS (P = 0.033). Despite the influence of rs919266 and rs9576 on BST2 expression being still undetermined, a preventive role by BST2 polymorphisms was found during HIV-1 infection.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/genética , Antígenos CD/genética , Progresión de la Enfermedad , VIH-1/fisiología , Transmisión Vertical de Enfermedad Infecciosa , Madres , Polimorfismo Genético , Complicaciones Infecciosas del Embarazo/genética , Síndrome de Inmunodeficiencia Adquirida/fisiopatología , Adulto , Femenino , Proteínas Ligadas a GPI/genética , VIH-1/crecimiento & desarrollo , Humanos , Inmunidad Innata/genética , Recién Nacido , Masculino , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , ZambiaRESUMEN
ABSTRACT HPV types 16 and 18 were studied in paraffin-fixed cervical biopsy collected in southern Brazil. HPV 16, HPV 18 and co-infection HPV 16/18 were identified in 10/57 (17.5%), 4/57 (7%) and in 43/57 (75.4%) samples, respectively. Southern Brazil has one of the highest prevalence rates of HPV 16/18 reported.
Asunto(s)
Humanos , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Cuello del Útero/patología , Infecciones por Papillomavirus/virología , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Coinfección/virología , Biopsia , Brasil/epidemiología , Cuello del Útero/virología , Prevalencia , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/epidemiología , Papillomavirus Humano 16/clasificación , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/clasificación , Papillomavirus Humano 18/genética , Coinfección/patología , Coinfección/epidemiologíaRESUMEN
ABSTRACT HPV types 16 and 18 were studied in paraffin-fixed cervical biopsy collected in southern Brazil. HPV 16, HPV 18 and co-infection HPV 16/18 were identified in 10/57 (17.5%), 4/57 (7%) and in 43/57 (75.4%) samples, respectively. Southern Brazil has one of the highest prevalence rates of HPV 16/18 reported.
RESUMEN
BACKGROUND The time of progression towards AIDS can vary greatly among seropositive patients, and may be associated with host genetic variation. The NR1I2 (PXR) gene, a ligand-activated transcription factor, regulates the transcription immune pathway genes and can therefore be targets of viral replication mechanisms influencing time of progression to AIDS. OBJECTIVE To verify the association of single nucleotide polymorphisms (SNPs) rs3814057, rs6785049, rs7643645, and rs2461817 in the NR1I2 (PXR) gene with progression to AIDS in HIV-1 infected patients. METHODS Blood samples were obtained from 96 HIV-1 positive individuals following informed consent. DNA was isolated and genotyped through real time polymerase chain reaction (PCR) for the presence of SNPs in the NR1I2. Questionnaires on socio-demographic features and behaviors were answered and time of progression to AIDS was estimated based on medical chart analysis. FINDINGS Patients with the GG genotype for rs7643645 were shown to be related with a more rapid disease progression when compared to GA and AA genotypes. This result was maintained by the Multivariate Cox Regression considering sex, ethnicity, and presence of HLA-B*57, HLA-B*27, and CCR5del32 polymorphisms. MAIN CONCLUSIONS Recent studies reported the expression of the nuclear receptors in T-Lymphocytes, suggesting their possible role in the immune response. In addition, nuclear receptors have been shown to inhibit the HIV replication, although no such mechanism has been thoroughly elucidated to date. This is the first time an association between NR1I2 polymorphism and time of progression to AIDS is reported and supports an apparent relationship between the gene in the immune response and identifies another genetic factor influencing AIDS progression.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Síndrome de Inmunodeficiencia Adquirida/genética , Síndrome de Inmunodeficiencia Adquirida/patología , Progresión de la Enfermedad , Polimorfismo Genético , GenotipoRESUMEN
Persistent infection with high-risk human papillomavirus (HR-HPV) has been associated with cervical cancer. Developing assays for the identification of these viral types is of great importance for monitoring patients and controlling strategies. The development of the MCHA (microplate colorimetric hybridization assay), a PCR-based method for identifying six of the most common HR-HPV types (HPV 16, 18, 31, 33, 39 and 45) is described. The MCHA combines the amplification with the GP5+/GP6+ consensus primers followed by PCR reverse hybridization with specific probes and detection through a colorimetric assay. The performance of the MCHA was evaluated using 108 DNA samples typed previously by the PapilloCheck(®). The agreement between both methods was 69.4% for HPV 16; 79.1% for HPV 45; 82.4% for HPV 18; 93.6% for HPV 31; 87.9% for HPV 33, and 17.6% for HPV 39. The assay had higher sensitivity than the Papillocheck(®), particularly for identifying HPV 16 and 18. The MCHA seemed to be sensitive and specific for the identification of the most prevalent HPV types in invasive cervical cancer, HPV 16, 18, 45, 33 and 31. It requires low-cost reagents and common laboratory apparatus.
Asunto(s)
Técnicas de Genotipaje/métodos , Hibridación de Ácido Nucleico/métodos , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Proteínas de la Cápside/genética , Colorimetría , Femenino , Genotipo , Humanos , Proteínas Oncogénicas Virales/genética , Infecciones por Papillomavirus/virología , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/virologíaRESUMEN
Typical human immunodeficiency virus-1 subtype B (HIV-1B) sequences present a GPGR signature at the tip of the variable region 3 (V3) loop; however, unusual motifs harbouring a GWGR signature have also been isolated. Although epidemiological studies have detected this variant in approximately 17-50% of the total infections in Brazil, the prevalence of B"-GWGR in the southernmost region of Brazil is not yet clear. This study aimed to investigate the C2-V3 molecular diversity of the HIV-1B epidemic in southernmost Brazil. HIV-1 seropositive patients were ana-lysed at two distinct time points in the state of Rio Grande do Sul (RS98 and RS08) and at one time point in the state of Santa Catarina (SC08). Phylogenetic analysis classified 46 individuals in the RS98 group as HIV-1B and their molecular signatures were as follows: 26% B"-GWGR, 54% B-GPGR and 20% other motifs. In the RS08 group, HIV-1B was present in 32 samples: 22% B"-GWGR, 59% B-GPGR and 19% other motifs. In the SC08 group, 32 HIV-1B samples were found: 28% B"-GWGR, 59% B-GPGR and 13% other motifs. No association could be established between the HIV-1B V3 signatures and exposure categories in the HIV-1B epidemic in RS. However, B-GPGR seemed to be related to heterosexual individuals in the SC08 group. Our results suggest that the established B"-GWGR epidemics in both cities have similar patterns, which is likely due to their geographical proximity and cultural relationship.