Impact of HLA allele-KIR partners on sexually transmitted HIV-1 infection.

HLA-I/KIR genotypes influence HIV-1 disease progression and viral load, but their role in primary infection is uncertain. Inconsistent results from previous studies suggest that the inoculum size and transmission route-parenteral vs. sexual-may influence this association. We conducted a GWAS in a population of people living with HIV-1 and HIV-1-exposed seronegative individuals exposed to the virus through the sexual route. Our data do not support any role of the HLA/KIR system in susceptibility to sexually transmitted HIV-1 infection. The genetics basis of HIV-1 viral load and disease progression are distinct from the genetics of HIV resistance, a paradox worth exploring.

IFNL4 genotype influences the rate of HIV-1 seroconversion in men who have sex with men.

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).

Serologic study of Bartonella sp. infection among human population of Southern Spain.

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.

Serologic study of Bartonella sp. infection among human population of Southern Spain / Estudio serológico de la infección por Bartonella sp. en la población humana del sur de España

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.

Distribution of Interferon Lambda 4 Single Nucleotide Polymorphism rs11322783 Genotypes in Patients with COVID-19.

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.

No association of a risk variant for severe COVID-19 with HIV protection in three cohorts of highly exposed individuals.

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.

CD46 Genetic Variability and HIV-1 Infection Susceptibility.

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.

Phylogeography of Hyalomma (Euhyalomma) lusitanicum (Acarina, Parasitiformes, Ixodidae) in Andalusia based on mitochondrial cytochrome oxidase I gene.

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).

Serologic study of Bartonella sp. infection among human population of Southern Spain.

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.

Complement C4 Gene Copy Number Variation Genotyping by High Resolution Melting PCR.

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.