CCR5∆32 and SDF1 3'A: Gene Variants, Expression and Influence on Biological Markers for the Clinical Progression to AIDS among HIV-1 Virus Controllers in a Mixed Population of the Amazon Region of Brazil.

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.

STING and cGAS gene expressions were downregulated among HIV-1-infected persons after antiretroviral therapy.

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.

TNFA -308G>A and IL10 -1082A>G polymorphisms seem to be predictive biomarkers of chronic HCV infection.

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.

Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-neuroinflammatory functions. We hypothesized that ANXA1 gene expression may be dysregulated in HTLV-1-infected HAM/TSP patients. METHODS: This study involved 37 individuals infected with HTLV-1, including 21 asymptomatic (AS) carriers and 16 with HAM/TSP, and a control group of 30 individuals negative for HTLV-1 and HTLV-2. For AS HTLV-1-positive and HAM/TSP patients, ANXA1 and formyl peptide receptor (FPR1, FPR2 and FPR3) expression and HTLV-1 proviral load (PVL) in peripheral blood cells were evaluated by real-time quantitative PCR (qPCR), and plasma AnxA1 levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: ANXA1 gene expression was increased in the AS group compared with the HAM/TSP and control groups, but the differences were not statistically significant. FPR1 gene expression was higher in patients with HTLV-1 than in controls (AS, p = 0.0032; HAM/TSP, p < 0.0001). Plasma AnxA1 levels were higher in the AS group than in the HAM/TSP group (p = 0.0045), and PVL was higher in patients with HAM/TSP than in AS individuals (p = 0.0162). The use of a combined ROC curve using Annexin 1 levels and proviral load significantly increased the sensitivity and specificity to predict progression to HAM/TSP (AUC = 0.851 and AUC = 0.937, respectively, to AUC = 1000). CONCLUSIONS: Our results suggest that AnxA1 may be dysregulated in HAM/TSP patients. Serological detection of AnxA1 in association with proviral load may provide a prognostic biomarker for HTLV-1-associated neurodegenerative disease.

The challenge of describing the epidemiology of HTLV in the Amazon region of Brazil.

HTLV-1 was the first described human retrovirus and was soon found to be associated with severe clinical diseases, including a devastating lymphoma/leukemia and other inflammatory diseases. Although HTLV-2 is not usually pathogenic, it is widely distributed among native Indian populations in Brazil, particularly in the Amazon region of the country. Presently, HTLV spreads mainly by the sexual route and from mother to child, and virus persistence is an active biological factor aiding its transmission. Recently, the use of illicit drugs has been shown to be an additional risk factor, showing the influence of new habits on the epidemiology of HTLV in the region. Despite the detection of the virus in several different populations in the Amazon region of Brazil for almost 30 years, the exact prevalence of HTLV-1/2 is not well defined. The original biases in sampling and the selection of epidemiologically unsuitable populations were commonly repeated in most prevalence studies, generating unreliable and conflicting figures that do not represent the actual prevalence of HTLV. The improvements in clinical and laboratory facilities have resulted in the description of several clinical manifestations that were previously unknown in the region. The extent of the spread of the virus must be defined in this region, which is the largest geographical area of the country. As prophylaxis advances toward the use of vaccines against HTLV-1, it is important to determine who is at risk of being infected and developing a disease to successfully implement preventive measures, particularly as proposals are made to eradicate the virus among humans.

Sex and FOXP3 gene rs2232365 polymorphism may be associated with the clinical and pathological aspects of chronic viral diseases.

BACKGROUND: The forkhead box protein 3 (FOXP3) transcription factor is one of the main markers of immunological suppression in different pathological profiles, and the presence of polymorphic variants may alter the gene expression of this factor. Despite descriptions of an association between the presence of the rs2232365 polymorphism and chronic diseases, the role of the sex variant in this context has not yet been elucidated, as the FOXP3 gene is located on the human sex chromosome X. RESULTS: To contribute to this topic, 323 women and 373 men were enrolled in the study, of which 101 were diagnosed with chronic viral liver diseases (39 women and 62 men), 67 with HTLV-1 infection (44 women and 23 men), 230 with coronary artery disease (91 women and 139 men) and 298 healthy and uninfected blood donors (149 women and men). They were genotyped for the rs2232365 polymorphism. The rs2232365 polymorphism was associated with clinical and pathological aspects and biomarkers of viral infections only in men, with functional differences between different infections. CONCLUSIONS: A relationship is suggested between sex and FOXP3 rs2232365 polymorphism, resulting in different biological repercussions.

NGF (-198C > T, Ala35Val) and p75NTR (Ser205Leu) gene mutations are associated with liver function in different histopathological profiles of the patients with chronic viral hepatitis in the Brazilian Amazon.

BACKGROUNDS: Neural growth factor (NGF) is a neurotrophin that can interact with the p75NTR receptor and initiate a cascade of reactions that determines cell survival or death, and both are associated with the physiology of liver tissue. Single nucleotide polymorphisms (SNPs) in the NGF and p75NTR genes have been investigated in different pathologies; however, there are no studies that have analyzed their biological roles in the hepatic microenvironment. In the present study, we evaluated the impact of SNPs in these genes on the maintenance of liver function at different stages of inflammation and fibrosis in patients with chronic viral liver disease in the Brazilian Amazon. METHODS: The SNPs -198C > T, Arg80Gln, Val72Met, Ala35Val, Ala18Ala and Ser205Leu were genotyped by real-time PCR in samples from patients with chronic viral hepatitis stratified by stage of inflammation and liver fibrosis. Histopathological, viral load (VL), liver enzyme and comorbidities data were obtained from updated medical records. Other aspects were highlighted by applied epidemiological questionnaires. RESULTS: The -198C/T and Ala35Val polymorphisms in NGF were associated with changes in histopathological profiles, VL and liver enzymes. Ser205Leu polymorphism in p75NTR was associated only with changes in VL and liver enzymes. Polymorphic frequencies were variable among different ethnic populations, mainly for biologically relevant polymorphisms. A multifactorial network of interactions has been established based on genetic, virological, behavioral and biochemical aspects. CONCLUSION: Mutations in the NGF (-198C > T, Ala35Val) and p75NTR (Ser205Leu) genes, within the list of multifactorial aspects, are associated with liver function in different histopathological profiles of patients with chronic viral liver disease in the Brazilian Amazon.

Immune escape mutations in HIV-1 controllers in the Brazilian Amazon region.

BACKGROUND: Human immunodeficiency virus (HIV-1) infection is characterized by high viral replication and a decrease in CD4+ T cells (CD4+TC), resulting in AIDS, which can lead to death. In elite controllers and viremia controllers, viral replication is naturally controlled, with maintenance of CD4+TC levels without the use of antiretroviral therapy (ART). METHODS: The aim of the present study was to describe virological and immunological risk factors among HIV-1-infected individuals according to characteristics of progression to AIDS. The sample included 30 treatment-naive patients classified into three groups based on infection duration (> 6 years), CD4+TC count and viral load: (i) 2 elite controllers (ECs), (ii) 7 viremia controllers (VCs) and (iii) 21 nonviremia controllers (NVCs). Nested PCR was employed to amplify the virus genome, which was later sequenced using the Ion PGM platform for subtyping and analysis of immune escape mutations. RESULTS: Viral samples were classified as HIV-1 subtypes B and F. Greater selection pressure on mutations was observed in the group of viremia controllers, with a higher frequency of immunological escape mutations in the genes investigated, including two new mutations in gag. The viral sequences of viremia controllers and nonviremia controllers did not differ significantly regarding the presence of immune escape mutations. CONCLUSION: The results suggest that progression to AIDS is not dependent on a single variable but rather on a set of characteristics and pressures exerted by virus biology and interactions with immunogenetic host factors.

Prevalence of syphilis in female sex workers in three countryside cities of the state of Pará, Brazilian Amazon.

BACKGROUND: Syphilis is a sexually transmitted infection (STI) transmitted from person to person mainly by sexual intercourse or through vertical transmission during pregnancy. Female sex workers (FSWs) are exposed especially to syphilis infection, and besides all the efforts to control the spread of STIs, syphilis prevalence is still rising, mainly occurring in low-income countries. This study aimed to investigate the syphilis prevalence, demographic characteristics and sexual habits among FSWs in the Amazon region of Brazil. METHODS: A cross-sectional study was carried out including 184 FSWs from 3 countryside cities of the state of Pará, Amazon region of Brazil. A venereal disease research laboratory test and an indirect immunoenzyme assay to test antibodies against Treponema pallidum were used for screening syphilis infection, while sexual habits and demographic data information were collected through a semi-structured questionnaire. Data was analyzed comparing groups with/without syphilis. Poisson regression models were used to estimate the reasons of prevalence (RP). RESULTS: The overall prevalence of syphilis was 14.1% (95% CI = 9.8-17.8). FSWs had between 15 and 56 years of age, most were unmarried (65.7%), had attended less than 8 years of formal education (64.1%), had between 10 and 20 partners per week (64.1%), and reported no previous history of STIs (76.1%) and regular use of condom (52.7%). Low level of education attending up to the primary school (RP adjusted = 3.8; 95% CI = 1.4-9.2) and high frequency of anal sex during the past year (RP adjusted = 9.3; 95% CI = 3.5-28.7) were associated with a higher prevalence of syphilis. CONCLUSIONS: A high prevalence of syphilis among FSWs in the Brazilian Amazon region was identified, showing that syphilis is more likely to be transmitted in FSW working in low-income areas, which is attributed to the low level of education. Anal intercourse was found as a risk factor associated with syphilis. Health programs focused on risk populations appear as a rational way to control syphilis spread, which is a rising problem in Brazil and in other several countries.

Isolation of the Arawete and Asurini Indians keeps the tribes free from HTLV infection during 36 years of follow-up.

Arawete and Asurini Indian tribes were revisited after a 36-year follow-up in search of HTLV infections. 46 persons (23 from each tribe) were tested for HTLV-1/2 antibodies and viral DNA. None were positive; this was probably because of their social/cultural isolation from neighboring tribes where HTLV-2c is hyperendemic.

High prevalence of human T-lymphotropic virus 2 (HTLV-2) infection in villages of the Xikrin tribe (Kayapo), Brazilian Amazon region.

BACKGROUND: Studies have shown that the human T-lymphotropic virus 2 (HTLV-2) is endemic in several indigenous populations of the Brazilian Amazon and molecular analyses have shown the exclusive presence of HTLV-2 subtype 2c among the indigenous groups of this geographical region. METHODS: The present study characterizes the prevalence of HTLV-2 infection in three new villages of the Xikrin tribe, in the Kayapo group, according to their distribution by sex and age. The study included 263 samples from individuals from the Kateté, Djujeko and Oodjã villages. Plasma samples were tested for the presence of anti-HTLV-1/2 antibodies using enzyme-linked immunosorbent assays (ELISA). Seropositive samples were confirmed using real-time PCR, nested PCR and sequencing. RESULTS: The serological and molecular results confirmed the sole presence of HTLV-2 in 77 (29%) samples, with a prevalence of 38% among women and 18% among men. In these communities, it was found that the prevalence of HTLV-2 infection increased with age. Nucleotide sequences (642 bp, 5'LTR) from eight samples were subjected to phylogenetic analysis by the neighbor-joining method to determine the viral subtype, which confirmed the presence of HTLV-2c. CONCLUSIONS: The results of the present study establish the presence of HTLV-2 infection in three new villages of the Xikrin tribe and confirm the high endemicity of the infection in the Kayapo indigenous group of the Brazilian Amazon.

Seroprevalence of HIV, HTLV, CMV, HBV and rubella virus infections in pregnant adolescents who received care in the city of Belém, Pará, Northern Brazil.

BACKGROUND: Prenatal tests are important for prevention of vertical transmission of various infectious agents. The objective of this study was to describe the prevalence of human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis B virus (HBV), cytomegalovirus (CMV), rubella virus and vaccination coverage against HBV in pregnant adolescents who received care in the city of Belém, Pará, Brazil. METHODS: A cross-sectional study was performed with 324 pregnant adolescents from 2009 to 2010. After the interview and blood collection, the patients were screened for antibodies and/or antigens against HIV-1/2, HTLV-1/2, CMV, rubella virus and HBV. The epidemiological variables were demonstrated using descriptive statistics with the G, χ2 and Fisher exact tests. RESULTS: The mean age of the participants was 15.8 years, and the majority (65.4%) had less than 6 years of education. The mean age at first intercourse was 14.4 years, and 60.8% reported having a partner aged between 12 and 14 years. The prevalence of HIV infection was 0.3%, and of HTLV infection was 0.6%. Regarding HBV, 0.6% of the participants had acute infection, 9.9% had a previous infection, 16.7% had vaccine immunity and 72.8% were susceptible to infection. The presence of anti-HBs was greater in adolescent between 12 and 14 years old (28.8%) while the anti-HBc was greater in adolescent between 15 and 18 years old (10.3%). Most of the adolescents presented the IgG antibody to CMV (96.3%) and rubella (92.3%). None of the participants had acute rubella infection, and 2.2% had anti-CMV IgM. CONCLUSIONS: This study is the first report of the seroepidemiology of infectious agents in a population of pregnant adolescents in the Northern region of Brazil. Most of the adolescents had low levels of education, were susceptible to HBV infection and had IgG antibodies to CMV and rubella virus. The prevalence of HBV, HIV and HTLV was similar to that reported in other regions of Brazil. However, the presence of these agents in this younger population reinforces the need for good prenatal follow-up and more comprehensive vaccination campaigns against HBV due to the large number of women susceptible to the virus.

GBV-C/HIV-1 coinfection is associated with low HIV-1 viral load and high CD4+ T lymphocyte count.

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.

Lower genetic variability of HIV-1 and antiretroviral drug resistance in pregnant women from the state of Pará, Brazil.

BACKGROUND: The present study aimed to describe the genetic diversity of HIV-1, as well as the resistance profile of the viruses identified in HIV-1 infected pregnant women under antiretroviral therapy in the state of Pará, Northern Brazil. METHODS: Blood samples were collected from 45 HIV-1 infected pregnant to determine the virus subtypes according to the HIV-1 protease (PR) gene and part of the HIV-1 reverse transcriptase (RT) gene by sequencing the nucleotides of these regions. Drug resistance mutations and susceptibility to antiretroviral drugs were analyzed by the Stanford HIV Drug Resistance Database. RESULTS: Out of 45 samples, only 34 could be amplified for PR and 30 for RT. Regarding the PR gene, subtypes B (97.1%) and C (2.9%) were identified; for the RT gene, subtypes B (90.0%), F (6.7%), and C (3.3%) were detected. Resistance to protease inhibitors (PI) was identified in 5.8% of the pregnant, and mutations conferring resistance to nucleoside reverse transcriptase inhibitors were found in 3.3%, while mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors were found in 3.3%. CONCLUSIONS: These results showed a low frequency of strains resistant to antiretroviral drugs, the prevalence of subtypes B and F, and the persistent low transmission of subtype C in pregnant of the state of Pará, Brazil.

Immunological and virological characterization of HIV-1 viremia controllers in the North Region of Brazil.

BACKGROUND: A rare phenotype of clinical non-progressors to AIDS is not well understood and the new protocol for universal treatment, may block the understanding of viral control thus it is crucial to define this controversial group. METHODS: A cohort of 30 persons followed a criteria for viremia control groups 1 (VC1; n = 2) and 2 (VC2; n = 7) and non-viral controllers (NC; n = 21) including number of years of diagnosis, LTCD4+, LTCD8+ counts, plasma viral load and the absence of ART; 241 uninfected control persons were matched to age and sex. Infected persons were regularly examined and submitted to two or three annual laboratory measurements. Polymorphisms and allele frequencies of CCR5Δ32 and SDF1-3'A were detected in the genomic DNA. Plasma levels of cytokines (IL-2, IL-4, IL-5, IL-9, IL-10, IL-13, IL-17 and IFN-y) were measured. RESULTS: The group investigated is originated from a miscigenetic population and demographic and social characteristics were not significantly relevant. LTCD4+ median values were higher among VC than NC, but significantly lower than uninfected controls. Evolution of LTCD4+ and LTCD8+ counts, showed a slight increase of LTCD4+ among VC, but a significant decrease in the NC. The percentage of annual change in LTCD4+ was also significantly different between the groups. LTCD4+/LTCD8+ ratio was inverted but not significant among the VC, thus the ratio may be a useful biomarker for the VC. A clear signature indicated a change from Th1 to Th2 cytokine profiles from VC to NC, respectively. CONCLUSIONS: The knowledge of viral controllers characteristics in different population groups is important to define a strict universal definition for the sake of learning about the pathogenesis of HIV-1. Data on LTCD4+ seems to be stable and repetitive from published data, but the LTCD8+ response and the significance of LTCD4+/LTCD8+ ratio values are in need to further exploration as biomarkers. The change from Th1 to Th2 cytokine profile may help to design and adjust specific treatment protocols for the group.

Human T-lymphotropic virus 1aA circulation and risk factors for sexually transmitted infections in an Amazon geographic area with lowest human development index (Marajó Island, Northern Brazil).

BACKGROUND: This cross-sectional study evaluated the prevalence of infection with human T-lymphotropic virus 1 and 2 (HTLV-1 and HTLV-2) in a population from the municipalities of Anajás, Chaves, São Sebastião da Boa Vista (SSBV) and Portel in the Marajó Archipelago and correlated these data with the epidemiological characteristics of the study population. METHODS: A total of 1899 biological samples were evaluated. The samples were screened for the presence of anti-HTLV antibodies using an enzyme-linked immunosorbent assay (ELISA), and infection was confirmed using conventional polymerase chain reaction (PCR), real-time PCR and nucleotide sequencing. RESULTS: Eleven samples (0.58%) were seropositive for HTLV, but molecular analysis confirmed positivity in only two samples (0.11%). Nucleotide sequencing and phylogenetic analysis indicated that the two samples positive for HTLV-1 that were isolated in Chaves belonged to the Cosmopolitan subtype 1 (HTLV-1a) and Transcontinental subgroup (A). CONCLUSION: Our results confirmed the presence of Cosmopolitan Transcontinental HTLV-1 in the Marajó Archipelago, Amazon region, and the majority of the population revealed a lack of knowledge about sexually transmitted infections, which increases the risk of dissemination of HTLV and other agents.

HBV Viral Load and Liver Enzyme Levels May Be Associated with the Wild MBL2 AA Genotype.

The present study investigated the frequencies of rs1800450 (MBL ⁎B, G>A), rs1800451 (MBL ⁎C, G>A), and rs5030737 (MBL ⁎D, C>T) polymorphisms in exon 1 of the MBL2 gene among patients with chronic viral hepatitis. Blood samples from patients infected with hepatitis B virus (HBV; n = 65), hepatitis C virus (HCV; n = 92), and a noninfected control group (n = 300) were investigated. The presence of polymorphisms was detected using a real-time polymerase chain reaction to correlate with liver disease pathogenesis and fibrosis staging according to the Metavir classification. The genotypic and allelic frequencies showed no significant differences between the groups, but patients with active HBV and the wild AA genotype presented a positive correlation between increased transaminase and HBV DNA levels and the presence of mild to moderate fibrosis. Patients with HCV and the wild AA genotype presented mild inflammation and higher HCV RNA levels, although the same association was not observed for the fibrosis scores. The results suggest that the mutations in exon 1 of the MBL2 gene do not contribute directly to the clinical and laboratory features of HCV and HBV infections, but further studies should be performed to confirm whether the wild AA genotype has indirect effect on disease progression.

IL28B gene polymorphisms and Th1/Th2 cytokine levels might be associated with HTLV-associated arthropathy.

The present study is the first investigation of the association between single nucleotide polymorphisms (SNPs - rs8099917, rs12979860 and rs8103142) of the IL28B gene and the development of human T-lymphotropic virus (HTLV)-associated arthropathy (HAA). Individuals with HAA exhibited low interleukin (IL) 6 (p<0.05) and high IL-10 (p<0.05) levels compared with asymptomatic patients. TNF-α/CD4(+) T cell count, TNF-α/CD8(+) T cell count and IFN-γ/proviral load positively correlated in asymptomatic patients. The allelic and genotypic frequencies did not differ between patients with HAA and asymptomatic patients. Seven haplotypes were detected in the investigated population, with haplotype CCT (p<0.05) being the most frequent among the HTLV-infected individuals, while haplotype TTG (p<0.05) was detected in the group with HAA only. Compared with asymptomatic patients, individuals with HAA and genotype TT (rs8099917) exhibited larger numbers of CD8(+) T cells (p<0.05) and higher proviral load levels (p<0.05). Those patients with HAA and genotypes CC (rs12979860) and TT (rs8103142) exhibited high TNF-ß (p<0.05) and IFN-γ (p<0.05) levels. Those patients with HAA and genotype CT/TT (rs12979860) exhibited high IL-10 levels (p<0.05). These results suggest that haplotypes CCT and TTG might be associated with susceptibility to HTLV infection and progression to HAA, respectively. Genotype TT (rs8099917) might be a risk factor for elevation of the proviral load and CD8(+) T cell count. In addition, genotypes CC (rs12979860) and TT (rs8103142) seem to be associated with increased TNF-ß and IFN-γ levels.

Prevalence and risk behaviour for human immunodeficiency virus 1 infection in Marajó Island, Northern Brazil.

BACKGROUND: Human immunodeficiency virus 1 (HIV-1) infection is a global public health problem, but, so far, there is no published information regarding the epidemiology of HIV-1 in Marajó Archipelago (Pará, Brazil). AIM: The present study reports the occurrence of infection by HIV-1 in four municipalities of the Marajó Island, Pará, Brazil. SUBJECTS AND METHODS: A total of 1877 samples were collected from volunteer blood donors (1296 women and 551 men) living in the municipalities of Anajás, Chaves, Portel and São Sebastião da Boa Vista. Information about risk behaviour assessment was obtained from a questionnaire. Plasma samples were tested for the presence of anti-HIV antibodies using serological tests. The infection was confirmed by nucleic acid amplification assays. RESULTS: Twelve samples were seropositive for HIV by ELISA. Western blot analysis showed four positive samples, eight indeterminate patterns and one found to be negative. Molecular analysis revealed three positive samples. Risk factors for HIV-1 infection included absence of condoms during sexual intercourse (41.3%, São Sebastião da Boa Vista), use of illicit drugs (5.8%, Anajás) and early initiation of sexual activities, from 10-15 years (30.7%). CONCLUSION: Although the study indicates a low HIV-1 prevalence in Marajó Island, some factors may increase the risk for HIV-1 and these include early sexual initiation, unprotected sexual intercourse and the use of illicit drugs.

HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis Is Not Associated with SNP rs12979860 of the IL-28B Gene.

The present study investigated the association between the rs12979860 polymorphism in the IL-28B gene and HTLV-1 infection as well as the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1-infected patients (26 HAM/TSP symptomatic and 53 asymptomatic) and 300 seronegative healthy controls were investigated. Plasma levels of the cytokines TNF-α, TNF-ß, IL-8, IL-10, IL-6, and IFN-γ from infected patients were measured using an indirect enzyme-linked immunosorbent assay. The HTLV proviral load was measured using a real-time PCR assay, and T-cell subset counts were determined by flow cytometry. Real-time PCR was used to genotype the rs12979860 SNP. The allelic and genotypic distributions displayed no significant differences among the investigated groups. No significant association between the serum cytokine levels and the presence of the rs12979860 SNP in symptomatic and asymptomatic subjects was observed. A positive correlation (p = 0.0015) between TNF-ß and IFN-γ was observed in the asymptomatic group, but a positive correlation was only observed (p = 0.0180) between TNF-α and IL-6 in the HAM/TSP group. The proviral load was significantly higher in HAM/TSP patients than in asymptomatic subjects. The present results do not support a previous report indicating an association between the SNP rs12979860 and HAM/TSP outcome.