ABSTRACT
Interleukin-6 (IL-6), a pro-inflammatory cytokine, is an important regulator of the inflammatory immune response. We aimed to assess the association of common single nucleotide polymorphisms (SNPs) in IL-6 (rs1800795 G > C, rs1800797 A > G) and interleukin-6 receptor (IL-6R) (rs2228145 A > C) genes with HIV-1 infection, AIDS progression, and response to treatment. In this case-control study involving 199 individuals living with HIV-1 and 200 HIV-uninfected controls, we conducted genotyping of IL-6/IL-6R SNPs using TaqMan real-time PCR assays. Soluble IL-6 levels were measured using ELISA. No associations were found between the investigated SNPs and HIV infection. However, a significant association was noted between the C-G and G-A haplotypes and susceptibility to HIV-1 infection. Additionally, a significant association was revealed between HIV-1 RNA viral loads and IL-6 SNP G > C in the post-treatment HIV group. Interestingly, we observed a significant association between the investigated SNPs and protection against progression to AIDS, namely the IL-6 G > A SNP in its recessive model and the IL-6R A > C SNP in its codominant and dominant models. Nevertheless, we found no significant differences between IL-6 levels and the different genotypes and alleles of the IL-6 gene either before or after combination antiretroviral therapy. IL-6 promoter haplotypes are associated with susceptibility to HIV-1 infection. Furthermore, IL-6 A > G and IL-6R A > C polymorphisms have been associated with protection against AIDS progression. Interestingly, the IL-6 G > C SNP may affect the response to treatment in people living with HIV-1.
ABSTRACT
Chronic inflammation triggered by hepatitis B (HBV) and hepatitis C (HCV) viruses elevates interleukin 6 (IL-6) levels, activating pathways that cause liver damage and contribute to hepatocellular carcinoma (HCC) development. In this study, we assessed IL-6 levels and explored the correlation between the rs1800795 and rs1800797 variants of the IL-6 gene and the risk of developing HCC. We conducted a case-control study involving 314 participants. Among them, 157 were HCC patients (94 anti-HCV, 22 HBsAg and 41 metabolic dysfunction-associated steatotic liver disease [MASLD]) and 157 controls. Genotyping for IL-6 rs1800795 and rs1800797 polymorphisms was performed using real-time polymerase chain reaction (PCR). Additionally, plasma IL-6 levels were determined using enzyme-linked immunosorbent assay. The IL-6 levels were notably higher in patients compared to controls (p < .0001). Among HCC patients, those with MASLD exhibited higher plasma IL-6 levels than those with HCV and HBV (p = .003). In male HCC patients, IL-6 levels were significantly elevated compared to controls (p < .0001). Similarly, female patients showed significantly higher IL-6 levels compared to female controls, though still lower than in male HCC patients (p = .023). However, no significant difference was observed in IL-6 levels between male and female HCC patients (p = .129). Contrastingly, the genotype and allele distributions of the rs1800795 and rs1800797 polymorphisms in the IL-6 gene displayed no association with HCC development (all p > .05). In Moroccan HCC patients, chronic liver inflammation is characterized by elevated levels of IL-6, potentially playing a role in the progression of liver disease and tumourigenesis.
Subject(s)
Carcinoma, Hepatocellular , Genetic Predisposition to Disease , Interleukin-6 , Liver Neoplasms , Polymorphism, Single Nucleotide , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/blood , Interleukin-6/blood , Interleukin-6/genetics , Male , Female , Liver Neoplasms/genetics , Liver Neoplasms/blood , Middle Aged , Morocco , Case-Control Studies , Adult , Aged , Genotype , Biomarkers, Tumor/blood , Biomarkers, Tumor/geneticsABSTRACT
BACKGROUND: Hepatitis A virus (HAV) is the common cause of acute hepatitis worldwide. Indeed, hepatitis A is endemic in developing countries such in Morocco and most residents are exposed in childhood. The characterisation of circulating strains of HAV remains crucial to understand the virological evolution and geo-temporal characteristics, which are essential for controlling infections and outbreaks. The purpose of the current study was the detection and characterisation of HAV strains circulating in Morocco by performing serological test, RT-PCR, sequencing and phylogenetic analysis. METHODS: In this cross-sectional study, 618 suspected acute hepatitis cases were examined by Architect HAV abIgM. Of the 162 positives, 64 underwent RNA extraction. None of the suspected cases was immune to HAV and none of them had received a blood transfusion. Samples found positive by RT-PCR using primers targeting the VP1/VP2A junction and the VP1/VP3 capsid region of HAV were subjected to sequencing and phylogenetic analyses. RESULTS: HAV Acute infection rate was 26.2% [95% CI, 22.8-29.9], while viraemia reached 45% (29/64) after amplification of the VP3/VP1 region. Phylogenetic analysis of the VP1/2A segment revealed the presence of sub-genotypes IA and IB. Eighty-seven percent of the strains belonged to the subgenotype IA, while twelve percent to IB subgenotype. CONCLUSION: This first molecular study of acute hepatitis A in Morocco provided information about genetic diversity of HAV, revealing the co-circulating of only two subgenotypes (IA and IB). Notably, subgenotype IA was found to be the predominant subgenotype in Morocco.
Subject(s)
Hepatitis A virus , Hepatitis A , Humans , Hepatitis A/epidemiology , Cross-Sectional Studies , Phylogeny , Morocco/epidemiology , Hepatitis A virus/genetics , Genotype , Acute Disease , RNA, Viral/genetics , RNA, Viral/analysisABSTRACT
Chronic inflammation and immune activation are a hallmark of HIV-1 infection. In this study, we assessed inflammation biomarkers in a cohort of people living with HIV-1 (PLWH) before and after long-term suppressive combined antiretroviral therapy (cART). A single-center prospective cohort study was conducted to assess inflammatory biomarkers in 86 cART-naive PLWH and after receiving suppressive cART and 50 uninfected controls. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and soluble CD14 (sCD14) were measured using enzyme-linked immunosorbent assay (ELISA). No significant difference was found in IL-6 levels between cART-naïve PLWH and controls (p = 0.753). In contrast, TNF-α level showed a significant difference between cART naïve-PLWH and controls (p = 0.019). Interestingly, IL-6 and TNF-α levels were significantly decreased in PLWH after cART (p < 0.0001). The sCD14 showed no significant difference between cART-naïve patients and controls (p = 0.839) and similar levels were observed in pre- and post-treatment (p = 0.719). Our results highlight the critical importance of early treatment to reduce inflammation and its consequences during HIV infection.
Subject(s)
HIV Infections , HIV-1 , Humans , Prospective Studies , HIV Infections/drug therapy , Interleukin-6 , Lipopolysaccharide Receptors , Tumor Necrosis Factor-alpha , Inflammation , BiomarkersABSTRACT
Non-primate hepacivirus (NPHV) is a homolog of hepatitis C virus and has been isolated from dogs and horses. Data on NPHV prevalence and distribution are not complete, and there is a particular lack of reports from the African continent. The present study represents the first investigation of NPHV prevalence in horses and dogs in North Africa. Blood was collected from 172 horses and 36 dogs at different locations in Morocco, and screened for NPHV RNA using nested PCR targeting 5'UTR and NS3 regions and analyzed for anti-NPHV NS3 antibody using a Gaussia luciferase immunoprecipitation system-to determine seroprevalence. Eight sequences of the NS3 region isolated from positive serum samples were targeted for phylogenetic analysis. Horses and dogs showed respective NPHV RNA positivity rates of 10.5% and 5.5%, and seroprevalences of 65.7% and 8.33%. Juvenile horses appeared more susceptible to infection, with a 23.5% NHPV RNA positivity rate. Seropositivity was more extensive in mares than stallions (77.14% vs. 46.27%, p < 0.0001). Phylogenetically, that NPHV NS3 genes isolated from horses and dog are clustered together. The NPHV strains we detected showed no correlation with geographic location within Morocco. In conclusion, Moroccan horses showed much evidence of previous and/or current NPHV infection, with young age and female sex as noted potential risk factors. Interestingly, NPHV is circulating in dogs as well as horses, suggesting that it has crossed species barriers and that horses and dogs are potential vectors by which an ancestor to hepatitis C virus was transmitted into human populations.
Subject(s)
Dog Diseases/epidemiology , Hepacivirus/physiology , Hepatitis C/veterinary , Horse Diseases/epidemiology , Animals , Dog Diseases/transmission , Dog Diseases/virology , Dogs , Female , Hepacivirus/classification , Hepacivirus/genetics , Hepatitis C/epidemiology , Hepatitis C/transmission , Hepatitis C/virology , Horse Diseases/transmission , Horse Diseases/virology , Horses , Male , Morocco/epidemiology , Phylogeny , Prevalence , Seroepidemiologic StudiesABSTRACT
BACKGROUND: It has been reported that interferon-λ3 (IFNL3)might influence the pathogenesis and clearance of human papillomavirus (HPV) infection. The impact of IFNL3 single-nucleotide polymorphism (SNP) on HPV infection is currently unknown. The aim of this study was to investigate the association between variants in the IFNL3 region and HPV infection in women with human immunodeficiency virus (HIV) infection. METHODS: A total of 236 HIV patients, including 65 HPV-negative and 171 HPV DNA-positive women, were enrolled into this study. The IFNL3 rs12979860 polymorphism was genotyped using a predesigned TaqMan SNP genotyping assay. RESULTS: Data showed no significant differences in genotypes or allele frequencies between the HPV DNA-positive and the HPV-negative women (p > 0.05). After dividing the HPV-positive women according to cytology results into patients with abnormal and normal lesions, the genotype and allele distribution of the SNP did not significantly differ between the 2 groups (p > 0.05). CONCLUSIONS: Our results showed that the IFNL3 rs12979860 polymorphism is not a major determinant of the susceptibility to HPV infection and their progression to abnormal cervical lesions in women living with HIV.