ABSTRACT
BACKGROUND: Available data show that the epidemiological profile of most indigenous Brazilian populations is characterized by the coexistence of long-standing health problems (high prevalence of infectious and parasitic diseases, malnutrition, and deficiency diseases, such as anemia in children and women of reproductive age), associated with new health problems, especially those related to obesity (hypertension, type 2 diabetes mellitus and dyslipidemia). Based on this scenario, this study analyzed the nutritional profile of the adult population of seven indigenous peoples from the Brazilian Amazon in the years 2007 and 2021. METHODS: A total of 598 adults individuals were analyzed in 2007 (319 women and 279 men) and 924 in 2021 (483 women and 441 men), from seven indigenous peoples located in the state of Pará, who were assisted during health actions carried out in 2007 and in 2021. Body mass index classification used the World Health Organization criteria for adults: low weight, < 18.5 kg/m2; normal weight, ≥ 18.5 and < 25 kg/m2); overweight, ≥ 25 and < 30 kg/m2, and obesity, ≥ 30 kg/m2. A waist circumference (WC) < 90 cm in men and < 80 cm in women was considered normal. RESULTS: The data revealed heterogeneous anthropometric profiles, with a low prevalence of nutritional changes in the Araweté, Arara and Parakanã peoples, and high proportions of excess weight and abdominal obesity in the Kararaô, Xikrin do Bacajá, Asurini do Xingu and Gavião peoples, similar to or even higher than the national averages. CONCLUSION: Different stages of nutritional transition were identified in the indigenous peoples analyzed, despite apparently having been subjected to the same environmental pressures that shaped their nutritional profile in recent decades, which may indicate different genetic susceptibilities to nutritional changes. The evidence shown in this study strongly suggests the need to investigate in greater depth the genetic and environmental factors associated with the nutritional profile of Brazilian indigenous peoples, with assessment of diet, physical activity and sociodemographic and socioeconomic variables that enable the development of appropriate prevention and monitoring measures.
Subject(s)
Indians, South American , Obesity, Abdominal , Overweight , Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Brazil/epidemiology , Indians, South American/statistics & numerical data , Indigenous Peoples/statistics & numerical data , Obesity/epidemiology , Obesity/ethnology , Obesity, Abdominal/epidemiology , Obesity, Abdominal/ethnology , Overweight/epidemiology , Overweight/ethnology , PrevalenceABSTRACT
The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID.
Subject(s)
COVID-19 , Post-Acute COVID-19 Syndrome , Humans , Interferon-alpha , Interleukin-6 , Nucleotidyltransferases/genetics , Nucleotidyltransferases/metabolism , Signal Transduction/genetics , Tumor Necrosis Factor-alpha/geneticsABSTRACT
Introduction: Mannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19. Methods: Blood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively. Results: The frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p< 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p< 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p< 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed. Discussion: The results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19.
Subject(s)
COVID-19 , Mannose-Binding Lectin , Humans , Tumor Necrosis Factor-alpha/genetics , Interleukin-6/genetics , Cytokines/genetics , Post-Acute COVID-19 Syndrome , COVID-19/genetics , Polymorphism, Genetic , Mannose-Binding Lectin/geneticsABSTRACT
CCR5Δ32 and SDF1-3'A polymorphisms were investigated in a cohort of viremia controllers, without the use of therapy, along with their influence on CD4+ T lymphocytes (TLs), CD8+ TLs, and plasma viral load (VL). The samples were analyzed from 32 HIV-1-infected individuals classified as viremia controllers 1 and 2 and viremia non-controllers, from both sexes, mostly heterosexuals, paired with 300 individuals from a control group. CCR5∆32 polymorphism was identified by PCR amplification of a fragment of 189 bp for the wild-type allele and 157 bp for the allele with the ∆32 deletion. SDF1-3'A polymorphism was identified by PCR, followed by enzymatic digestion (restriction fragment length polymorphism) with the Msp I enzyme. The relative quantification of gene expression was performed by real-time PCR. The distribution of allele and genotype frequencies did not show significant differences between the groups. The gene expression of CCR5 and SDF1 was not different between the profiles of AIDS progression. There was no significant correlation between the progression markers (CD4+ TL/CD8+ TL and VL) and the CCR5∆32 polymorphism carrier status. The 3'A allele variant was associated with a marked loss of CD4+ TLs and a higher plasma VL. Neither CCR5∆32 nor SDF1-3'A was associated with viremia control or the controlling phenotype.
Subject(s)
Acquired Immunodeficiency Syndrome , Chemokine CXCL12 , HIV Infections , Receptors, CCR5 , Female , Humans , Male , Acquired Immunodeficiency Syndrome/genetics , Biomarkers , Brazil , Chemokine CXCL12/genetics , Disease Progression , Gene Frequency , HIV-1 , Receptors, CCR5/genetics , ViremiaABSTRACT
TNF-α is a Th1 cytokine profile active in the control of Mycobacterium tuberculosis infection, IL-10 is associated with persistence of bacterial infection. The aim of the study was to investigate the association of TNFA -308G/A and IL10 -819C/T polymorphisms and TNFA and IL10 gene expression levels with pulmonary and extrapulmonary tuberculosis (n = 200) and control (n = 200). The individuals were submitted to genotyping and quantification of gene expression performed by real-time quantitative polymerase chain reaction (qPCR). No association was observed between the frequencies of polymorphisms evaluated and pulmonary tuberculosis. The frequency of polymorphic genotypes for TNFA -308G/A were associated with the extrapulmonary tuberculosis (p = 0.0445). The levels of TNFA expression were lower in the pulmonary tuberculosis group than in the control (p = 0.0009). There was a positive correlation between the levels of TNFA and IL10 in patients with pulmonary tuberculosis (r = 0.560; p = 0.0103). Reduced levels of TNFA expression may promote the formation of an anti-inflammatory microenvironment, favoring the persistence of the bacillus in the host, contributing to the establishment of pulmonary tuberculosis.
Subject(s)
Interleukin-10 , Tuberculosis, Pulmonary , Humans , Interleukin-10/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Brazil , Genotype , Tumor Necrosis Factor-alpha/genetics , Gene Expression , Gene FrequencyABSTRACT
Several factors are associated with the development of different clinical forms of tuberculosis (TB). The present study evaluated epidemiological variables and cytokine levels in samples from 89 patients with TB (75 with pulmonary TB and 14 with extrapulmonary TB) and 45 controls. Cytokines were measured by flow cytometry (Human Th1/Th2/Th17 Cytometric Bead Array kit). The TB group had a higher frequency of individuals who were 39 years of age or older, married, with primary education or illiterate and had a lower family income (p < 0.05). All individuals with extrapulmonary TB reported that they were not working, and the main reasons were related to disease symptoms or treatment. The levels of IFN-γ (OR = 4.06) and IL-4 (OR = 2.62) were more likely to be elevated in the TB group (p = 0.05), and IFN-γ levels were lower in patients with extrapulmonary TB compared to those with pulmonary TB (OR = 0.11; p = 0.0050). The ROC curve was applied to investigate the diagnostic accuracy of IFN-γ levels between the different clinical forms of tuberculosis, resulting in high AUC (0.8661; p < 0.0001), sensitivity (93.85%) and specificity median (65.90%), suggesting that IFN-γ levels are useful to differentiate pulmonary TB from extrapulmonary TB. The dysregulation of pro- and anti-inflammatory cytokine levels represent a risk for the development of TB and contribute to the pathogenesis of the disease, especially variation in IFN-γ levels, which may determine protection or risk for extrapulmonary TB.
ABSTRACT
In Brazil, the coronavirus disease 2019 (COVID-19) epidemic spread rapidly in a heterogeneous way, mainly due to the different socioeconomic and behavioral characteristics of different regional populations and different evaluation periods. We performed a cross-sectional study including 1,337 individuals (first wave = 736/second wave = 601) after the first two waves of COVID-19 in the city of Belém, the capital of the state of Pará. The detection of IgG anti-SARS-CoV-2 antibodies was performed using an enzyme-linked immunosorbent assay test followed by statistical analysis using the RStudio program. Our results showed an increase in the seroprevalence (first wave= 39.1%/second wave= 50.1%) of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies in the population of Belém from the first to the second pandemic wave. Advanced age, primary or secondary education level, lack of social isolation, and a low frequency of protective mask use were considered risk factors for SARS-CoV-2 infection during the first wave compared to the second wave. This study is one of the firsts to provide important information about the dynamics of virus circulation and the groups vulnerable to exposure in the two major periods. Our data emphasize the socioeconomic characteristics of the affected population and that nonpharmacological prevention measures are crucial for combating the pandemic.
Subject(s)
COVID-19 , Antibodies, Viral , Brazil/epidemiology , COVID-19/epidemiology , Cross-Sectional Studies , Humans , Immunoglobulin G , Risk Factors , SARS-CoV-2 , Seroepidemiologic StudiesABSTRACT
Introduction: The absence of nursing care plans aimed at people living with HTLV-1 (PLHTLV) led us to develop and test a proposed nursing care plan based on the evaluation of 55 PLHTLV to outline interventions according to the clinical stage. Methods: After interviews with symptomatic patients, nursing diagnoses were made using the NANDA International Nursing Diagnoses (The International Nursing Knowledge Association). Subsequently, interventions were selected through the Classification of Nursing Interventions (NIC), and expected results were selected through the Classification of Nursing Outcomes (NOC). Results: The actual diagnoses included (ii) chronic pain, (iii) impaired urinary elimination, and (iv) sexual dysfunction; the health promotion diagnosis was (i) risk-prone health behavior; and the risk diagnoses were (i) risk of feeling powerless and (ii) risk of falls in adults. Nursing care must prevent the lack of adherence to monitoring, establish goals and promote family involvement. A safe home environment requires intervention for fall prevention. Full support in understanding pharmacological and non-pharmacological therapies for chronic pain is needed. Interventions allow patients with impaired urinary function to be reintroduced to society. For sexual dysfunction, it is necessary to discuss safe sex and behavioral changes. Regarding risk behaviors, it is necessary to guide the patient/family, adapt language to the education level of these individuals, and help them better accept the condition, among other guidelines. Conclusion: The development of a nursing care plan for PLHTLV is essential for preventing the rapid progression of disease and the improvement of the quality of life of PLHTLV and should be included in the multidisciplinary approach to the secondary level of prevention of HTLV-1.
ABSTRACT
Introduction: Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy (HAM) restricts activities of daily living (ADLs), affecting health and quality of life. Occupational therapy is used to promote independence during ADL in people living with HTLV (PLHTLV). Objective: To quantify the clinical aspects, levels of functionality, performance in ADLs and occupational roles of PLHTLV and propose an occupational therapeutic intervention. Method: A cross-sectional, descriptive, observational study was designed with 40 PLHTLV monitored at two referral laboratories of the Federal University of Pará. The Evandro Chagas Research Institute Neurological Disability Scale (EIPEC-2), the Barthel Index and the Occupational Roles Identification List were applied. The G test and Fisher's exact test (to identify associations between qualitative variables), the Mann-Whitney test (to identify associations between quantitative variables) and Pearson correlation analysis (to identify associations between the total Barthel Index and EIPEC-2 scores) were performed with Microsoft Excel and BioEstat 5.0, and the significance level was set at p ≤ 0.05. Results: Motor aspects, the presence of spasticity, sensory aspects, and pain in the lumbar region and lower limbs were significantly (p = 0.0002) higher among symptomatic individuals, who also had more difficulties urinating, traveling up and down stairs and transferring from a chair to a bed. Being a worker, performing housework and socializing (with friends or family members) were the most affected activities among HAM patients. Conclusion: The impact of HAM on PLHTLV should include an intervention plan with occupational therapists in rehabilitation programs to create an important third-level prevention initiative, which may help achieve short-, medium-, and long-term goals. Asymptomatic PLHTLV should also be able to prevent future ADL impairment.
ABSTRACT
The dysregulation of cytokine production can lead to an inefficient immune response, promoting viral persistence that induces the progression of chronic viral hepatitis. The study investigated the association of the IL6-174G/C polymorphism with changes in cytokine levels and its influence on the persistence and progression of chronic hepatitis caused by HBV and HCV in 72 patients with chronic hepatitis B (HBV), 100 patients with hepatitis C (HCV), and a control group of 300 individuals. The genotyping of the IL6-174G/C polymorphism was performed by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). HCV patients with the wild-type genotype (GG) had a higher viral load (p = 0.0230). The plasma levels of IL-6 were higher among patients infected with HBV and HCV than among the control group (p < 0.0001). Patients with HCV were associated with increased inflammatory activity (A2−A3; p < 0.0001). In hepatitis C, carriers of the GG genotype had higher levels of IL-6 (p = 0.0286), which were associated with A2−A3 inflammatory activity (p = 0.0097). Patients with A2−A3 inflammatory activity and GG genotype had higher levels of IL-6 than those with the GC/CC genotype (p = 0.0127). In conclusion, the wild-type genotype for the IL6-174G/C polymorphism was associated with high levels of IL-6 and HCV viral load and inflammatory activity, suggesting that this genotype may be a contributing factor to virus-induced chronic infection.
Subject(s)
Hepatitis C, Chronic , Hepatitis C , Brazil/epidemiology , Cytokines/genetics , Genotype , Hepacivirus/genetics , Hepatitis B virus , Hepatitis C, Chronic/genetics , Humans , Interleukin-6/geneticsABSTRACT
Apoptosis of macrophages infected by Mycobacterium tuberculosis via Fas-FasL is an important immune mechanism against infection. This study investigated the association of tuberculosis (TB) with the presence of the polymorphisms FAS -670A/G and FASL -124A/G, the levels of sFas and sFasL, and the gene expression of FASL and cytokines. Samples of 200 individuals diagnosed with TB and 200 healthy controls were evaluated. Real-time PCR (genotyping and gene expression) and ELISA (dosages of sFas, sFasL, IFN-γ, and IL-10) tests were performed. There was no association of FAS -670A/G and FASL -124A/G polymorphisms with TB. The TB group exhibited high plasma levels of sFas and reduced plasma levels of sFasL (p < 0.05). The correlation analysis between these markers revealed a positive correlation between the levels of sFas and sFasL, sFasL and FASL expression, and between sFas and FASL expression (p < 0.05). In the TB group, there was a positive correlation between FASL expression and IFN-γ levels and higher levels of IL-10 compared to IFN-γ (p < 0.05). High levels of sFas and reduced levels of sFasL and FASL expression may contribute to the inhibition of apoptosis in infected cells and represent a possible bacterial resistance resource to maintain the infection.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Humans , Interleukin-10/genetics , Fas Ligand Protein/genetics , Enzyme-Linked Immunosorbent Assay , Tuberculosis/genetics , Gene ExpressionABSTRACT
BACKGROUND: Genetic changes may induce dysregulated cytokine production and affect the progression of the chronic disease caused by the hepacivirus C (HCV) because the balance of pro- and anti-inflammatory cytokines determines the outcome of infection. This study evaluated the TNFA -308G>A and IL10 -1082A>G polymorphisms in the susceptibility and progress of chronic hepatitis C. METHOD: The study included 101 samples from patients with chronic hepatitis C and 300 samples from healthy donors. Polymorphisms were typed by real-time PCR and were analyzed for associations with histopathological parameters (according to METAVIR classification) and HCV viral load. RESULTS: The polymorphic genotype for the TNFA -308G>A variant was not present in the group of patients with chronic hepatitis C and its absence could be associated with protection against HCV infection (p = 0.0477). Patients with the polymorphic genotype of the IL10 -1082A>G polymorphism had higher HCV viral load than wild-type patients (p = 0.0428). Neither polymorphism was associated with different levels of necroinflammatory activity or fibrosis scores. CONCLUSION: Our results suggest the polymorphic genotype at TNFA -308G>A as protective against chronic HCV infection, and the polymorphic genotype at the IL10 -1082A>G variant associated with higher HCV viral load. Further studies must be performed in order to confirm these associations.
Subject(s)
Hepacivirus , Hepatitis C, Chronic , Biomarkers , Genotype , Hepatitis C, Chronic/genetics , Humans , Interleukin-10/genetics , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Tumor Necrosis Factor-alphaABSTRACT
The present study evaluated the IL8-251 A/T polymorphism in samples from 74 patients with chronic hepatitis B (HBV), 100 patients with chronic hepatitis C (HCV), and 300 healthy donors (CG). The correlations of this polymorphism with plasma IL-8 and disease stage were calculated. Polymorphisms were identified by real-time PCR. IL-8 was measured by enzyme-linked immunosorbent assay. The IL8-251 A/T genotype was not associated with susceptibility to infection by HBV or HCV. The wild-type allele (A) was associated with higher levels of inflammation (p = 0.0464) and fibrosis scores (p = 0.0016) in the HBV group, representing an increased risk for increased inflammatory activity (OR = 1.84; p = 0.0464) and for high fibrosis scores (OR = 2.63; p = 0.0016). Viral load was higher in HBV patients with polymorphic genotypes (TA and TT) at the IL8-251 A/T polymorphism than in those with the wild-type genotype (p = 0.0272 and p = 0.0464, respectively). Plasma IL-8 was higher among patients infected with HBV or HCV than in the control group (p = 0.0445 and p = 0.0001, respectively). The polymorphic genotype was associated with lower IL-8 than the wild-type genotype in the HBV group (p = 0.0239) and the HCV group (p = 0.0372). The wild-type genotype for IL8-251 A/T and high IL-8 were associated with a worse prognosis for infections; therefore, they may contribute to viral persistence and the development of more severe forms of chronic viral liver diseases.
Subject(s)
Hepatitis B, Chronic , Interleukin-8 , Adult , Genetic Profile , Humans , Middle AgedABSTRACT
An inefficient immune response against the hepatitis C virus (HCV), combined with viral evasion mechanisms, is responsible for the chronicity of infection. The need to evaluate the innate mechanisms of the immune response, such as TLR3 and IFN-λ3, and their relationship with the virus-host interaction is important for understanding the pathogenesis of chronic hepatitis C. The present study aimed to investigate the gene expressions of TRL3 and IFNL3 in liver tissue, seeking to evaluate whether these could be potential biomarkers of HCV infection. A total of 23 liver biopsy samples were collected from patients with chronic HCV, and 8 biopsies were collected from healthy control patients. RNA extraction, reverse transcription and qPCR were performed to quantify the relative gene expressions of TLR3 and IFNL3. Data on the viral load; AST, ALT, GGT and AFP levels; and the viral genotype were collected from the patients' medical records. The intrahepatic expression of TLR3 (p = 0.0326) was higher in chronic HCV carriers than in the control group, and the expression of IFNL3 (p = 0.0037) was lower in chronic HCV carriers than in the healthy control group. The expression levels of TLR3 (p = 0.0030) and IFNL3 (p = 0.0036) were higher in the early stages of fibrosis and of necroinflammatory activity in the liver; in contrast, TLR3 and IFNL3 expressions were lower in the more advanced stages of fibrosis and inflammation. There was no correlation between the gene expression and the serum viral load. Regarding the initial METAVIR scale scores, liver transaminase levels were lower in patients with advanced fibrosis when correlated with TLR3 and IFNL3 gene expressions. The results suggest that in the early stages of the development of hepatic fibrosis, TLR3 and IFN-λ3 play important roles in the antiviral response and in the modulation of the tolerogenic liver environment because there is a decrease in the intrahepatic expressions of TLR3 and IFNL3 in the advanced stages of fibrosis, probably due to viral evasion mechanisms.
Subject(s)
Hepacivirus , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/genetics , Interferons/genetics , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Toll-Like Receptor 3/genetics , Biomarkers , Biopsy , Cross-Sectional Studies , Disease Susceptibility , Gene Expression , Gene Expression Profiling , Genome, Viral , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/virology , Humans , Interferons/metabolism , Male , Severity of Illness Index , Toll-Like Receptor 3/metabolism , Viral LoadABSTRACT
Sexually transmitted infections (STIs) represent a worldwide public health problem and, although many of them are curable, they continue to be neglected, especially in areas with a low human development index, such as in the northern region of Brazil. This review describes the results of 30 years of studies at the Virus Laboratory at the Federal University of Pará, including the prevalence and molecular epidemiology of HIV-1, HTLV-1/2, HPV, HBV, Treponema pallidum and Chlamydia trachomatis among urban and non-urban populations, and also in vulnerable groups in the Brazilian Amazon. Control strategies and challenges in preventing STIs are discussed considering this immense geographic region, where essential health services are unable to reach the entire population, especially the most vulnerable, such as female sex workers, people who use illicit drugs, remnants of quilombolos and indigenous communities.
Subject(s)
Epidemiological Monitoring , Public Health , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/prevention & control , Vulnerable Populations/statistics & numerical data , Brazil/epidemiology , Chlamydia Infections/epidemiology , HIV Infections/epidemiology , HIV Seropositivity , Prevalence , Sex Workers/statistics & numerical data , Sexual Behavior , Sexually Transmitted Diseases/parasitology , Sexually Transmitted Diseases/virologyABSTRACT
BACKGROUND: The HIV-1 epidemic is still considered a global public health problem, but great advances have been made in fighting it by antiretroviral therapy (ART). ART has a considerable impact on viral replication and host immunity. The production of type I interferon (IFN) is key to the innate immune response to viral infections. The STING and cGAS proteins have proven roles in the antiviral cascade. The present study aimed to evaluate the impact of ART on innate immunity, which was represented by STING and cGAS gene expression and plasma IFN-α level. METHODS: This cohort study evaluated a group of 33 individuals who were initially naïve to therapy and who were treated at a reference center and reassessed 12 months after starting ART. Gene expression levels and viral load were evaluated by real-time PCR, CD4+ and CD8+ T lymphocyte counts by flow cytometry, and IFN-α level by enzyme-linked immunosorbent assay. RESULTS: From before to after ART, the CD4+ T cell count and the CD4+/CD8+ ratio significantly increased (p < 0.0001), the CD8+ T cell count slightly decreased, and viral load decreased to undetectable levels in most of the group (84.85%). The expression of STING and cGAS significantly decreased (p = 0.0034 and p = 0.0001, respectively) after the use of ART, but IFN-α did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4+ T at the time of the first collection. CONCLUSIONS: ART provided immune recovery and viral suppression to the studied group and indirectly downregulated the STING and cGAS genes. In contrast, ART did not influence IFN-α. The expression of STING and cGAS was not correlated with the plasma level of IFN-α, which suggests that there is another pathway regulating this cytokine in addition to the STING-cGAS pathway.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections , Membrane Proteins/genetics , Nucleotidyltransferases/genetics , Cohort Studies , Gene Expression , HIV Infections/drug therapy , HIV-1/genetics , HIV-1/metabolism , Humans , Interferon-alpha/blood , Signal TransductionABSTRACT
The IFN-γ and TGF-ß1 cytokines perform antagonistic activities in the immune response, and polymorphisms in these genes may induce changes in their plasma levels and influence the course of chronic Hepacivirus C (HCV) infection. The present study evaluated the IFNG +874A/T and TGFB1 -509 C/T polymorphisms in 99 samples from patients with chronic hepatitis C and in 300 samples from healthy donors, and the present study also investigated the association of cytokine plasma level with disease stage. Polymorphisms were identified by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of the IFNG +874A/T polymorphic allele was not associated with susceptibility to HCV infection, but it was associated with lower inflammatory activity (p = 0.0432). The frequency of the TGFB1 -509C/T polymorphic (TT) genotype was associated with HCV infection (p = 0.0062) and a higher risk of infection (OR = 2.0465; p = 0.0091). Plasma levels of IFN-γ were higher in TT genotype carriers among the control (p = 0.0012) and HCV groups (p = 0.0064) as well as in patients with fibrosis (p = 0.0346) and patients with a high degree of inflammatory activity (p = 0.0381). The highest TGF-ß1 levels were found in HCV-infected (p = 0.0329) individuals and in TT genotype carriers. Patients with cirrhosis had higher TGF-ß1 (p = 0.0400). IFN-γ and TGF-ß1 levels showed a negative correlation (p = 0.0001). In conclusion, the TGFB1 -509C > T polymorphism is associated with a risk of developing chronic hepatitis C, leading to increased TGF-ß1, which inhibits IFN-γ production, contributing to the progression to cirrhosis.
Subject(s)
Hepatitis C, Chronic/genetics , Liver Cirrhosis/genetics , Transforming Growth Factor beta1/genetics , Case-Control Studies , Disease Progression , Female , Genetic Predisposition to Disease , Genotype , Hepacivirus , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/virology , Humans , Interferon-gamma/blood , Interferon-gamma/genetics , Liver Cirrhosis/blood , Liver Cirrhosis/virology , Male , Polymorphism, Genetic , Transforming Growth Factor beta1/blood , Viral LoadABSTRACT
BACKGROUND: Human polyomavirus 2 (HPyV2 or JCPyV) is persistent in the environment due to its excretion in urine and feces; it is detected in samples of wastewater, surface water and drinking water. A lack of basic sanitation and sewage collection results in the presence of this virus in food, especially in oysters, since they are bioaccumulators and are consumed in their natural form, thus posing a risk to human health. METHODS: This study investigated the frequency of HPyV2 in samples of oysters marketed in northeastern Pará State, Brazil, and optimized a real-time PCR (qPCR) protocol for the detection of an endogenous oyster control. A total of 217 oysters in 22 pools from five municipalities in the state of Pará were analyzed. Samples underwent dissection and total maceration of oyster tissue using a viral concentration technique, followed by DNA extraction with phenol-chloroform and amplification of the VP1 region for molecular detection via qPCR. RESULTS: HPyV2 was detected in 18.2% (4/22) of the pooled samples, with frequencies of 25, 20, 20 and 16% in the municipalities of Salinópolis, Augusto Corrêa, São Caetano de Odivelas and Curuçá, respectively. Notably, the sample pool from the municipality of Bragança did not have detectable HPyV2 and this was the only sampled location with a water treatment station. In this study, Crassostrea genus-specific primers (AFL52 ribosomal RNA gene) of oyster were developed for use as an endogenous control in the qPCR analysis, which will be useful for future studies. CONCLUSIONS: The detection of HPyV2 in oyster samples commercialized in the state of Pará shows the circulation of this virus in the studied municipalities. Thus, it is necessary to implement measures for improving sewage collection and basic sanitation to avoid contamination of water and food with HPyV2.
Subject(s)
Environmental Monitoring , Ostreidae/virology , Polyomavirus/isolation & purification , Water Microbiology , Animals , Brazil , Humans , Polyomavirus/genetics , Sewage/virology , Water PurificationABSTRACT
Contact with HCV triggers the activation of innate mechanisms responsible for initial infection control. Host cells expressed extra- or intracellularly molecules that promote recognition of pathogen-associated molecular patterns (PAMPs). Toll-like receptor 4 (TLR4), mannose-binding lectin (MBL) and C-reactive protein (CRP) are molecules available for HCV PAMP recognition. The present study evaluated TLR4, MBL and CRP gene expression in the hepatic tissue of chronic HCV carriers (n = 22) and the association of that expression with the pathogenesis of HCV as well as the progression of liver fibrosis. Liver biopsy specimens from the HCV group were divided according to the METAVIR classification: without fibrosis and/or mild fibrosis (F0-F1), moderate fibrosis (F2), and severe fibrosis and/or cirrhosis (F3-F4) and A0-A1 (absent or mild inflammation) and A2 (moderate inflammation); normal liver samples were used as a control (n = 8). The mRNA levels of the genes studied were quantified by real-time PCR, and plasma CRP and liver enzymes were measured using an automated system. CRP and MBL expression was significantly lower in the HCV group compared to that in the control group (p < .0001 and p = .0242, respectively). TLR4 expression was higher in the HCV group than in the control group (p = .0448) and was also significantly higher (p = .0314) with lower levels of necroinflammatory activity (A0-A1), with a significant correlation between the expression of MBL with TLR4 as well as a positive correlation between plasma levels and CRP expression in the HCV group (p = .0431). Hepatic TLR4, MBL and CRP expression showed no significant association with liver enzymes nor plasma viral load. Mechanisms of HCV escape seem to influence hepatic TLR4, MBL and CRP expression, resulting in a change in the transcription profile of these proteins of innate immunity, which may contribute to virus persistence, liver fibrogenesis and loss of normal liver function.
Subject(s)
C-Reactive Protein/genetics , Hepacivirus/physiology , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/virology , Liver/metabolism , Liver/virology , Mannose-Binding Lectin/genetics , Toll-Like Receptor 4/genetics , Adult , Aged , Biomarkers , Biopsy , Case-Control Studies , Disease Susceptibility , Female , Gene Expression , Hepatitis C, Chronic/diagnosis , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate , Liver/pathology , Liver Function Tests , Male , Middle Aged , Viral LoadABSTRACT
GB virus C (GBV-C) is a lymphotropic virus with a low level or non-existent replication in the liver. The interaction between HIV-1 and GBV-C apparently reduces the progression of HIV-1 infection to AIDS and improves the quality of life of HIV-1 infected individuals. A cross-sectional study was established to determine the possible effect of HIV-1/GBV-C coinfection on HIV-1 viral load and CD4+ T lymphocyte counts. Samples from 313 HIV-1 infected persons from the Virus Laboratory of the Federal University of Pará as well as demographic and clinical information were obtained from medical records. This study used a nested PCR method to determine GBV-C viremia. The prevalence of HIV-1/GBV-C coinfection was 17%. There were no significant differences in the distribution according to age, sex or ethnicity between the groups. The differences in HIV-1 viral load and CD4+ T lymphocyte count between the HIV-1 and HIV-1/GBV-C groups were highly significant, indicating that coinfection results in lower viral loads and higher CD4+ T lymphocyte counts compared to HIV-1 mono-infection. The results indicate a protective effect among coinfected individuals.