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1.
Enferm Infecc Microbiol Clin (Engl Ed) ; 40(4): 179-182, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35473988

RESUMO

INTRODUCTION: The purpose of this study was to determine the prevalence of IgG antibodies against Bartonella sp. in a randomly selected sample from the population of the patients of North Sanitary District of Jaén. METHODS: We used a commercially available immunofluorescent test (Focus-Technology IFA Bartonella quintana and B. henselae test). RESULTS: Six hundred five healthy individuals were divided by sex into three age groups. We detected that 13.55% and 11.07% subjects were IgG seropositive to B. henselae and B. quintana, respectively. CONCLUSIONS: Our data show that the prevalence of both Bartonella species in Andalusia (Southern Spain) is relatively high. No statistical difference in the seropositivity was observed among these groups. In both cases, the IgG antibody titers ranged from 1/128 to 1/512.


Assuntos
Infecções por Bartonella , Bartonella henselae , Bartonella , Doença da Arranhadura de Gato , Anticorpos Antibacterianos , Infecções por Bartonella/epidemiologia , Doença da Arranhadura de Gato/epidemiologia , Humanos , Imunoglobulina G , Espanha/epidemiologia
2.
Virulence ; 13(1): 757-763, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35481423

RESUMO

Individuals lacking interferon lambda 4 (IFNL4) protein due to a common null mutation (rs368234815) in the IFNL4 gene display higher resistance against several infections. The influence of IFNL4 on HIV-1 infection is still under discussion and conflicting results have been reported. This study intended to corroborate or refute the association of the null allele of IFNL4 and HIV-1 predisposition in a cohort of men who have sex with men (MSM). IFNL4 null genotype was assessed on 619 HIV-1-seronegative MSM who were followed for 36 months during a trial of a prophylactic vaccine against HIV-1. Of those, 257 individuals seroconverted during this period. A logistic regression model was constructed including demographic and IFNL4 genotype. In addition, a meta-analysis using data from the current study and other European populations was conducted. The null IFNL4 genotypes were correlated with lower HIV-1 seroconversion (Adjusted OR = 0.4 [95%CI: 0.2-0.8], P = 0.008) and longer time to seroconversion (889 vs. 938 days, P= 0.01). These results were validated by a meta-analysis incorporating data from other European populations and the result yielded a significant association of the IFNL4 null genotype under a dominant model with a lower probability of HIV-1 infection (OR=0.4 [95% CI: 0.3-0.6]; P= 1.3 x 10E-5).


Assuntos
Infecções por HIV , HIV-1 , Minorias Sexuais e de Gênero , Genótipo , Infecções por HIV/genética , HIV-1/genética , Homossexualidade Masculina , Humanos , Interferons , Interleucinas/genética , Masculino , Soroconversão
3.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 40(4): 1-4, Abril, 2022. mapas, tab
Artigo em Inglês | IBECS | ID: ibc-203481

RESUMO

IntroductionThe purpose of this study was to determine the prevalence of IgG antibodies against Bartonella sp. in a randomly selected sample from the population of the patients of North Sanitary District of Jaén.MethodsWe used a commercially available immunofluorescent test (Focus-Technology IFA Bartonella quintana and B. henselae test).ResultsSix hundred five healthy individuals were divided by sex into three age groups. We detected that 13.55% and 11.07% subjects were IgG seropositive to B. henselae and B. quintana, respectively.ConclusionsOur data show that the prevalence of both Bartonella species in Andalusia (Southern Spain) is relatively high. No statistical difference in the seropositivity was observed among these groups. In both cases, the IgG antibody titers ranged from 1/128 to 1/512.


IntroducciónEl propósito de este estudio fue determinar la prevalencia de anticuerpos IgG frente a Bartonella sp. en una muestra escogida al azar de la población de pacientes del Distrito Sanitario Norte de Jaén.MétodosSe ha utilizado una prueba de inmunofluorescencia disponible comercialmente (Focus-Technology IFA Bartonella quintana y prueba de B. henselae). Seiscientos cinco individuos sanos se dividieron por sexo en 3 grupos de edad.ResultadosDetectamos que el 13,55% y el 11,07% de los sujetos eran IgG seropositivos a B. henselae y B. quintana, respectivamente. En ambos casos, los títulos de anticuerpos IgG variaron de 1/128 a 1/512.ConclusiónNuestros datos muestran que la prevalencia de ambas especies de Bartonella en Andalucía (sur de España) es relativamente alta. No se observaron diferencias estadísticas en la seropositividad entre grupos de edad.


Assuntos
Humanos , Ciências da Saúde , Bartonella quintana , Espanha , Bacilos Gram-Negativos Anaeróbios Facultativos , Imunoglobulina G , Microbiologia , Doenças Transmissíveis , Estudos de Casos e Controles , Imunofluorescência
4.
Microorganisms ; 10(2)2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35208821

RESUMO

Type III interferons (IFN-III), also known as IFN-Lambda, have a pivotal role during SARS-CoV-2 infection. IFN-Lambda response among individuals is heterogeneous and its association with COVID-19 symptoms severity needs to be further clarified. We analyzed the genotype frequencies of IFNL4 single nucleotide polymorphism (SNP) rs11322783 in patients with COVID-19 (n = 128), in comparison with a validated data set of European healthy controls (n = 14152). The IFNL4 SNP was also analyzed according to the haematological and clinical parameters of patients with COVID-19. The distributions of IFNL4 genotypes among SARS-CoV-2 positive patients [TT/TT 41.4% (n = 53), TT/ΔG 47.7% (n = 61) and ΔG/ΔG 10.9% (n = 14)] and healthy controls were comparable. Different levels of white blood cells (p = 0.036) and neutrophils (p = 0.042) were found in the IFNL4 different genotypes in patients with COVID-19; the ΔG/ΔG genotype was more represented in the groups with low white blood cells and neutrophils. There were no differences in major inflammation parameters (C-reactive protein, D-dimer, Albumin, and Lactate-dehydrogenase (LDH)] and survival rate according to the IFNL4 genotypes. In conclusion, although patients with COVID-19 did not exhibit a different distribution of the IFNL4 SNP, the ΔG/ΔG genotype was associated with a lower count of immune cell populations. These findings need to be confirmed in larger groups of patients with COVID-19 and the role of IFNL4 SNP needs to be also investigated in other respiratory viral infections.

5.
PNAS Nexus ; 1(3): pgac138, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36741450

RESUMO

An extended haplotype on chromosome 3 is the major genetic risk factor for severe COVID-19. The risk haplotype, which was inherited from Neanderthals, decreases the expression of several cytokine receptors, including CCR5. Recently, a study based on three general population cohorts indicated that the minor allele of one of the variants in the haplotype (rs17713054) protects against HIV infection. We thus expected this allele to be over-represented in highly exposed individuals who remain uninfected (exposed seronegative individuals, ESN). To perform a meta-analysis, we genotyped rs17713054 in three ESN cohorts of European ancestry exposed to HIV through different routes. No evidence of association was detected in the single cohorts. The meta-analysis also failed to detect any effect of the variant on protection from HIV-1. The same results were obtained in a Cox-regression analysis for the time to seroconversion. An in-vitro infection assay did not detect differences in viral replication as a function of rs17713054 genotype status. We conclude that the rs17713054 minor allele is not associated with the ESN phenotype and does not modulate HIV infection in vitro.

6.
Cells ; 10(11)2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34831317

RESUMO

CD46 is the main receptor for complement protein C3 and plays an important role in adaptive immune responses. CD46 genetic variants are associated with susceptibility to several infectious and autoimmune diseases. Additionally, CD46 function can be subverted by HIV-1 to evade attack by complement, a strategy shared by viruses of other families. We sought to determine the association between CD46 gene variants and HIV-1 acquired through intravenous drug use (IDU) and sexual routes (n = 823). Study subjects were of European ancestry and were HIV-1 infected (n = 438) or exposed but seronegative (n = 387). Genotyping of the rs2796265 SNP located in the CD46 gene region was done by allele-specific real-time PCR. A meta-analysis merging IDU and sexual cohorts indicates that the minor genotype (CC) was associated with increased resistance to HIV-1 infection OR = 0.2, 95% CI (0.07-0.61), p = 0.004. The HIV-1-protective genotype is correlated with reduced CD46 expression and alterations in the ratio of CD46 mRNA splicing isoforms.


Assuntos
Predisposição Genética para Doença , Variação Genética , Infecções por HIV/genética , Proteína Cofatora de Membrana/genética , Feminino , Regulação da Expressão Gênica , Frequência do Gene/genética , Soronegatividade para HIV/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Abuso de Substâncias por Via Intravenosa/genética
7.
Exp Appl Acarol ; 85(1): 49-61, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34435267

RESUMO

The genetic population structure relationships of Hyalomma (Euhyalomma) lusitanicum in Andalusia (the south of the Iberian Peninsula) were examined using mtDNA sequence data from 887 bp of cytochrome oxidase subunit I (COI) gene. The sequence for the COI region was determined for 84 individuals collected in several localities of Andalusia, and 10 for other localities (i.e., five from Toledo, central Iberian Peninsula, four from Sicily (Italy) and one from Canary Island). Seventeen haplotypes were detected, including 27 polymorphic sites. The number of amino acid substitutions per site from mean diversity calculations for the entire population was 0.017. AMOVA analysis revealed a low gene flow that characterises the genetic population structure of this species in South Iberian Peninsula, with a haplotype diversity (h) value of 0.815. No geographically induced differentiation was observed, and separate evolutionary units were not detected. Our results indicate low genetic diversity across the geographical range of H. lusitanicum tick in Andalusia. Our data do not show any genetic discontinuity between the tick populations studied, including specimens from Canary Island and Sicily (Italy).


Assuntos
Complexo IV da Cadeia de Transporte de Elétrons , Ixodidae , Animais , Complexo IV da Cadeia de Transporte de Elétrons/genética , Genes Mitocondriais , Ixodidae/genética , Filogenia , Filogeografia
8.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33334612

RESUMO

INTRODUCTION: The purpose of this study was to determine the prevalence of IgG antibodies against Bartonella sp. in a randomly selected sample from the population of the patients of North Sanitary District of Jaén. METHODS: We used a commercially available immunofluorescent test (Focus-Technology IFA Bartonella quintana and B. henselae test). RESULTS: Six hundred five healthy individuals were divided by sex into three age groups. We detected that 13.55% and 11.07% subjects were IgG seropositive to B. henselae and B. quintana, respectively. CONCLUSIONS: Our data show that the prevalence of both Bartonella species in Andalusia (Southern Spain) is relatively high. No statistical difference in the seropositivity was observed among these groups. In both cases, the IgG antibody titers ranged from 1/128 to 1/512.

9.
Int J Mol Sci ; 21(17)2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32878183

RESUMO

BACKGROUND: Complement C4 gene copy number variation plays an important role as a determinant of genetic susceptibility to common diseases, such as systemic lupus erythematosus, schizophrenia, rheumatoid arthritis, and infectious diseases. This study aimed to develop an assay for the quantification of copy number variations in the C4 locus. METHODS: the assay was based on a gene ratio analysis copy enumeration (GRACE) PCR combined with high resolution melting (HRM) PCR. The test was optimized using samples of a known genotype and validated with 72 DNA samples from healthy blood donors. RESULTS: to validate the assay, standard curves were generated by plotting the C4/RP1 ratio values against copy number variation (CNV) for each gene, using genomic DNA with known C4 CNV. The range of copy numbers in control individuals was comparable to distributions observed in previous studies of European descent. CONCLUSIONS: the method herein described significantly simplifies C4 CNV diagnosis to validate the assay.


Assuntos
Complemento C4/análise , Complemento C4/genética , Variações do Número de Cópias de DNA , Predisposição Genética para Doença , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único , Genótipo , Humanos
10.
J Infect Dis ; 222(12): 2007-2011, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-32516401

RESUMO

Toll-like receptor 2 (TLR2) plays a key role in innate immune response recognizing molecular patterns expressed by pathogens. rs111200466 is a TLR2 promoter insertion/deletion polymorphism with contradictory data about its role in human immunodeficiency virus type 1 (HIV-1) infection. We analyzed rs111200466 in HIV-1 disease progression and showed a correlation with a faster progression to the CD4+ < 200 cells/µL outcome for deletion allele carriers (Cox regression analysis: hazard ratio, 2.4 [95% confidence interval, 1.4-4]; P = .001). When naive patients with CD4+ < 200 cells/µL started antiretroviral treatment, rs111200466-deletion carriers showed a trend toward a slower, recovery rate (time required to reach CD4+ > 350 cells/µL; Cox P = .36). Our data suggest rs111200466 as a prognosis factor for HIV-1 disease progression.


Assuntos
Contagem de Linfócito CD4 , Infecções por HIV/genética , Polimorfismo Genético , Receptor 2 Toll-Like/genética , Estudos de Coortes , Progressão da Doença , Feminino , HIV-1 , Humanos , Masculino , Prognóstico , Regiões Promotoras Genéticas , Análise de Sobrevida
11.
Clin Exp Rheumatol ; 38(5): 949-955, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32167874

RESUMO

OBJECTIVES: The TYK2 gene encodes a tyrosin kinase which is involved in multiple immune functions. A functional variant of this gene has been identified to play a protective role in multiple autoimmune diseases. The goal of this study was to evaluate the involvement of this variant of TYK2 in vasculitides [giant cell arteritis (GCA), ANCA-associated vasculitis (AAV) and IgA vasculitis (IgAV)] and viral infections [hepatitis C virus (HCV) and human immunodeficiency virus type I (HIV-1)]. METHODS: The study sample was composed of 13,745 European individuals. The genotyping was performed by Immunochip and TaqMan 5' allele discrimination assays and the allele frequencies were compared using PLINK. RESULTS: Although the results obtained did not reach the genome-wide level of significance, p-values at nominal significance were observed, suggesting that the TYK2 variant provides protection against two vasculitides: GCA (p=5.94E-3; OR (95%CI) = 0.56 (0.37-0.85) and AAV (p=6.79E-3; OR (95%CI) = 0.65 (0.47-0.89). However, this variant was not found to be associated with IgAV. No evidence was gained that the TYK2 variant confers susceptibility to HCV and HIV-1 infection. CONCLUSIONS: This is the first study to propose the association between the TYK2 and both GCA and AAV. Our findings also suggest that TYK2 does not play a relevant role in IgAV or in susceptibility to HCV and HVI-1.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Arterite de Células Gigantes , Infecções , Alelos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Frequência do Gene , Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Humanos , Polimorfismo de Nucleotídeo Único , TYK2 Quinase
12.
AIDS ; 34(1): 25-32, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634193

RESUMO

OBJECTIVES: Complement C3d receptor 2 (CR2) is the main receptor for complement protein C3d and plays an important role in adaptive immune responses. CR2 genetic variants are associated with susceptibility to systemic lupus erythematosus as well as to HIV-1 infection. In addition, CR2 function can be subverted by HIV-1 for an efficient entry into target cells; in a process known as antibody-dependent enhancement of viral infection. We sought to determine the association between CR2 gene variants with HIV-1 acquisition after vaccination with recombinant gp120 protein (Vax004 clinical trial). DESIGN AND METHODS: This is a retrospective cross-sectional study, comprising male volunteers of European ancestry including infected (n = 273) and uninfected (n = 402) vaccinees and placebo, who were genotyped for three single nucleotide polymorphisms (SNPs) in the CR2 gene region. RESULTS: An interaction was observed between the baseline sexual behavior and the SNP rs3813946 for higher risk of infection in vacinees (interaction term P = 0.02). This SNP was associated with increased susceptibility to HIV-1 infection after vaccination in volunteers with low behavioral risk odds ratio (95% confidence interval): 5.5 (1.4-21.7) P = 0.006 but not vaccinees with high behavioral risk or volunteers given placebo (P = 0.7). Moreover, CR2 genotype was strongly associated with the rate of HIV-1 acquisition after vaccination in low-risk volunteers [hazard odds ratio (95% confidence interval): 3.3 (1.6-7.0), P = 0.001]. CONCLUSION: The current study suggests that CR2 may play a role in HIV-1 acquisition after vaccination with rgp120 proteins.


Assuntos
Vacinas contra a AIDS/uso terapêutico , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/prevenção & controle , Receptores de Complemento 3d/genética , Adulto , Estudos Transversais , Predisposição Genética para Doença , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/genética , Humanos , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Comportamento Sexual , Vacinação , Vacinas Sintéticas/uso terapêutico
13.
Sci Rep ; 9(1): 9054, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227787

RESUMO

Due to the relation between lipids and Hepatitis C virus (HCV) life-cycle, we aimed to explore the existence of single nucleotide polymorphisms (SNPs) associated with low susceptibility to HCV-infection within lipid metabolism genes. This was a case-control study in three phases: (I) allelic frequencies of 9 SNPs within 6 genes were compared in 404 HCV-infected patients and 801 population controls; (II) results were validated in 602 HCV-infected individuals and 1352 controls; (III) results were confirmed in 30 HCV-exposed uninfected (EU) individuals. In phase I, only the LDLRAP1-rs4075184-A allele was differentially distributed in patients and controls (358 of 808 alleles [44.3%] and 807 of 1602 alleles [50.3%], respectively) (p = 0.004). In phase II, the A allele frequency was 547 of 1204 alleles (45.4%) in patients and 1326 of 2704 alleles (49.0%) in controls (p = 0.037). This frequency in EU was 36 of 60 alleles (60%), which was higher than that observed in patients from phase I (p = 0.018) and phase II (p = 0.027). The LDLRAP1-mRNA expression was lower in AA carriers than in non-AA carriers (median [Q1-Q3]: 0.85 [0.17-1.75] relative-units [ru] versus 1.71 [1.00-2.73] ru; p = 0.041). Our results suggest that LDLRAP1-rs4075184-A allele is associated with lower susceptibility to HCV-infection and with reduced expression of LDLRAP1-mRNA.


Assuntos
Predisposição Genética para Doença , Hepatite C/genética , Metabolismo dos Lipídeos/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
14.
Infect Genet Evol ; 73: 276-286, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31103723

RESUMO

Vitamin D (VitD) may modulate anti-HIV-1 responses modifying the risk to acquire the HIV-1-infection. We performed a nested case-control exploratory study involving 413 individuals; HIV-1-exposed seropositives (cases) and seronegatives (HESN) (controls) from three cohorts: sexually-exposed from Colombia and Italy and parenterally-exposed from Spain. The association and interactions of 139 variants in 9 VitD pathway genes, and in 14 antiviral genes with resistance/susceptibility (R/S) to HIV-1 infection was evaluated. Associations between variants and mRNA levels were also analyzed in the Colombian samples. Variants and haplotypes in genes of VitD and antiviral pathways were associated with R/S, but specific associations were not reproduced in all cohorts. Allelic heterogeneity could explain such inconsistency since the associations found in all cohorts were consistently in the same genes: VDR and RXRA of the VitD pathway genes and in TLR2 and RNASE4. Remarkably, the multi-locus genotypes (interacting variants) observed in genes of VitD and antiviral pathways were present in most HESNs of all cohorts. Finally, HESNs carrying resistance-associated variants had higher levels of VitD in plasma, of VDR mRNA in blood cells, and of ELAFIN and defensins mRNA in the oral mucosa. In conclusion, despite allelic heterogeneity, most likely due to differences in the genetic history of the populations, the associations were locus dependent suggesting that genes of the VitD pathway might act in concert with antiviral genes modulating the resistance phenotype of the HESNs. Although these associations were significant after permutation test, only haplotype results remained statistically significant after Bonferroni test, requiring further replications in larger cohorts and functional analyzes to validate these conclusions.


Assuntos
Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Imunidade Inata/genética , Vitamina D/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Variação Genética/genética , Genótipo , HIV-1 , Humanos , Itália , Masculino , Receptores de Calcitriol/genética , Espanha
15.
J Infect Dis ; 219(5): 772-776, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30289470

RESUMO

An interferon λ4 gene (IFNL4) knockout allele (rs368234815; TT) is associated with spontaneous and IFN-α-dependent cure of hepatitis C virus infection. The role of this polymorphism in the susceptibility to human immunodeficiency virus type 1 (HIV-1) infection is controversial. This study aimed to assess the association of this knockout IFNL4 variant and sexually transmitted HIV-1 infection. A total of 228 HIV-1-positive individuals and 136 HIV-exposed seronegative individuals were investigated for their association with IFNL4 rs368234815 genotypes. The IFNL4 ΔG functional allele is associated with increased susceptibility to HIV-1 infection through the sexual route (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.6; P = .004). A meta-analysis including a population of injection drug users suggests a codominant mode of inheritance of this risk factor (OR, 2.0; 95% CI, 1.3-3.2; P = .001).


Assuntos
Transmissão de Doença Infecciosa , Predisposição Genética para Doença , Infecções por HIV/genética , Infecções por HIV/transmissão , Interleucinas/genética , Deleção de Sequência , Feminino , Genótipo , Humanos , Masculino
16.
Infect Genet Evol ; 45: 20-25, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27539513

RESUMO

INTRODUCTION: CD209 is a receptor expressed in the dendritic cells involved in recognition of oligosaccharides present in several pathogens with a relevant impact on human health. SNPs located in the promoter region have been associated with HIV-1 susceptibility, although this finding has not been replicated in other populations. The objective of this study is to evaluate the association of CD209 promoter haplotypes with risk of HIV-1 infection in a cohort of Spanish male intravenous drug users (IDU) infected with hepatitis C virus (HCV) and to characterize the phenotypic effects of the associated variants. METHODS: We genotyped 4 SNPs of CD209 promoter in 295 HCV males exposed to HIV-1 infection by IDU, 165 HIV-1-infected and 130 exposed uninfected (EUI) and 142 healthy controls (HC). We have cloned the promoter variants in a reporter vector and evaluated the promoter activities in a cell culture model. CD209 mRNAs were measured in PBMC. RESULTS: Single-marker analysis revealed no significant allelic association with the risk of HIV-1 infection by parenteral route. Nevertheless, one haplotype was significantly overrepresented in EUI compared with HIV-1 positive patients and was associated with HIV-1 status (P=0.0008; OR: 0.43). Functional experiments suggested that the protective haplotype displayed lower transcriptional activity in vitro (P<0.05) and this was correlated with lower CD209 mRNA expression in PBMC (P=0.014). CONCLUSIONS: This study suggests that the promoter haplotypes of CD209 influence the risk of HIV-1 acquisition in IDU and that this association is correlated with the mRNA expression level.


Assuntos
Moléculas de Adesão Celular/genética , Usuários de Drogas/estatística & dados numéricos , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Haplótipos/genética , Lectinas Tipo C/genética , Regiões Promotoras Genéticas/genética , Receptores de Superfície Celular/genética , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adolescente , Adulto , Linhagem Celular , Feminino , Predisposição Genética para Doença/genética , Infecções por HIV/complicações , Hepatite C/complicações , Hepatite C/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Estudos Prospectivos , Espanha/epidemiologia , Abuso de Substâncias por Via Intravenosa/complicações , Adulto Jovem
17.
AIDS ; 29(14): 1895-7, 2015 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-26372394

RESUMO

The interferon (IFN)L4 polymorphism rs368234815 is associated with hepatitis C virus (HCV) spontaneous clearance and response to IFN-based treatments. The role of this polymorphism in HIV-1 infection is controversial. We investigated whether genetic variation at IFNL4 is associated to HIV-1 acquisition. The HCV protective allele TT was associated with decreased likelihood of HIV-1 infection in male intravenous drug users [odds ratio (OR): 0.3; P = 0.006], and this association was not modified by the genotype of CCR5. These results suggest that genetic susceptibility to HCV and HIV-1 infection shares common molecular pathways.


Assuntos
Resistência à Doença , Infecções por HIV/genética , Infecções por HIV/imunologia , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , HIV-1 , Hepatite C/genética , Hepatite C/imunologia , Humanos , Masculino , Estudos Prospectivos
18.
PLoS One ; 9(9): e106442, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25180498

RESUMO

The HAVCR2 gene encodes TIM-3, an immunoglobulin superfamily member expressed by exhausted CD8+ T cells during chronic viral infection. We investigated whether genetic variation at HAVCR2 modulates the susceptibility to HIV-1 acquisition; specifically we focused on a 3' UTR variant (rs4704846, A/G) that represents a natural selection target. We genotyped rs4704846 in three independent cohorts of HIV-1 exposed seronegative (HESN) individuals with different geographic origin (Italy and Spain) and distinct route of exposure to HIV-1 (sexual and injection drug use). Matched HIV-1 positive subjects and healthy controls were also analyzed. In all case-control cohorts the minor G allele at rs4704846 was more common in HIV-1 infected individuals than in HESN, with healthy controls showing intermediate frequency. Results from the three association analyses were combined through a random effect meta-analysis, which revealed no heterogeneity among samples (Cochrane's Q, p value = 0.89, I2 = 0) and yielded a p value of 6.8 ×10(-4). The minor G allele at rs4704846 was found to increase HAVCR2 expression after in vitro HIV-1 infection. Thus, a positively selected polymorphism in the 3' UTR, which modulates HAVCR2 expression, is associated with the susceptibility to HIV-1 infection. These data warrant further investigation into the role of TIM-3 in the prevention and treatment of HIV-1/AIDS.


Assuntos
Predisposição Genética para Doença , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/fisiologia , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Feminino , Estudos de Associação Genética , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade
19.
Mol Biol Evol ; 31(9): 2402-14, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24930137

RESUMO

The protein product of the myxovirus resistance 2 (MX2) gene restricts HIV-1 and simian retroviruses. We demonstrate that MX2 evolved adaptively in mammals with distinct sites representing selection targets in distinct branches; selection mainly involved residues in loop 4, previously shown to carry antiviral determinants. Modeling data indicated that positively selected sites form a continuous surface on loop 4, which folds into two antiparallel α-helices protruding from the stalk domain. A population genetics-phylogenetics approach indicated that the coding region of MX2 mainly evolved under negative selection in the human lineage. Nonetheless, population genetic analyses demonstrated that natural selection operated on MX2 during the recent history of human populations: distinct selective events drove the frequency increase of two haplotypes in the populations of Asian and European ancestry. The Asian haplotype carries a susceptibility allele for melanoma; the European haplotype is tagged by rs2074560, an intronic variant. Analyses performed on three independent European cohorts of HIV-1-exposed seronegative individuals with different geographic origin and distinct exposure route showed that the ancestral (G) allele of rs2074560 protects from HIV-1 infection with a recessive effect (combined P = 1.55 × 10(-4)). The same allele is associated with lower in vitro HIV-1 replication and increases MX2 expression levels in response to IFN-α. Data herein exploit evolutionary information to identify a novel host determinant of HIV-1 infection susceptibility.


Assuntos
Povo Asiático/genética , Resistência à Doença , Infecções por HIV/genética , Infecções por HIV/imunologia , Proteínas de Resistência a Myxovirus/genética , População Branca/genética , Biologia Computacional/métodos , Evolução Molecular , Variação Genética , HIV-1/patogenicidade , Haplótipos , Humanos , Modelos Genéticos , Proteínas de Resistência a Myxovirus/química , Filogenia , Seleção Genética
20.
PLoS One ; 9(4): e95515, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24748394

RESUMO

OBJECTIVES: The rs12979860 variant, linked to IL28B gene, predicts sustained viral response (SVR) to pegylated-interferon/ribavirin (pegIFN/RBV) therapy in Hepatitis C Virus genotype 1 or 4 (HCV-1/4)-infected patients. Recently, a functional variant, ss469415590, in linkage disequilibrium (LD) with rs12979860, has been discovered. Our objective was to assess the value of ss469415590 to predict SVR to pegIFN/RBV in Caucasian HCV-1/4-infected individuals and to compare its performance with that of rs12979860. METHODS: 272 Caucasian HCV-1/4-infected patients who completed a course of pegIFN/RBV were genotyped for both rs12979860 and ss469415590 markers. Logistic regression models including factors with univariate association with SVR and each genetic marker were elaborated. The area under the receiver operating-characteristic curve (AUROC) was calculated for each model and both were compared. RESULTS: Both markers were in LD (r2 = 0.82). For rs12979860, 66 (64.0%) CC versus 56 (33.1%) T allele carriers achieved SVR (Adjusted OR = 4.156, 95%CI = 2.388-7.232, p = 4.647×10-7). For ss469415590, 66 (66.0%) TT/TT versus 56 (32.5%) -G allele carriers (Adjusted OR = 4.783, 95%CI = 2.714-8.428, p = 6.153×10-8) achieved SVR. The AUROC of the model including rs12979860 was 0.742 (95%CI = 0.672-0.813) and of that based on ss469415590 was 0.756 (95%CI = 0.687-0.826) (p = 0.780). CONCLUSIONS: The ss469415590 variant shows an equivalent performance to predict SVR to pegIFN/RBV than the rs2979860 in Caucasian HCV-1/4-infected patients.


Assuntos
Alelos , Antivirais/uso terapêutico , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Interleucinas/genética , Interleucinas/uso terapêutico , Adulto , Coinfecção , Feminino , Seguimentos , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Curva ROC , Resultado do Tratamento , População Branca/genética
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