RESUMO
BACKGROUND: Diverse vaccination outcomes and protection levels among different populations pose a serious challenge to the development of an effective malaria vaccine. Co-infections are among many factors associated with immune dysfunction and sub-optimal vaccination outcomes. Chronic, asymptomatic viral infections can contribute to the modulation of vaccine efficacy through various mechanisms. Human Pegivirus-1 (HPgV-1) persists in immune cells thereby potentially modulating immune responses. We investigated whether Pegivirus infection influences vaccine-induced responses and protection in African volunteers undergoing whole P. falciparum sporozoites-based malaria vaccination and controlled human malaria infections (CHMI). METHODS: HPgV-1 prevalence was quantified by RT-qPCR in plasma samples of 96 individuals before, post vaccination with PfSPZ Vaccine and after CHMI in cohorts from Tanzania and Equatorial Guinea. The impact of HPgV-1 infection was evaluated on (1) systemic cytokine and chemokine levels measured by Luminex, (2) PfCSP-specific antibody titers quantified by ELISA, (3) asexual blood-stage parasitemia pre-patent periods and parasite multiplication rates, (4) HPgV-1 RNA levels upon asexual blood-stage parasitemia induced by CHMI. RESULTS: The prevalence of HPgV-1 was 29.2% (28/96) and sequence analysis of the 5' UTR and E2 regions revealed the predominance of genotypes 1, 2 and 5. HPgV-1 infection was associated with elevated systemic levels of IL-2 and IL-17A. Comparable vaccine-induced anti-PfCSP antibody titers, asexual blood-stage multiplication rates and pre-patent periods were observed in HPgV-1 positive and negative individuals. However, a tendency for higher protection levels was detected in the HPgV-1 positive group (62.5%) compared to the negative one (51.6%) following CHMI. HPgV-1 viremia levels were not significantly altered after CHMI. CONCLUSIONS: HPgV-1 infection did not alter PfSPZ Vaccine elicited levels of PfCSP-specific antibody responses and parasite multiplication rates. Ongoing HPgV-1 infection appears to improve to some degree protection against CHMI in PfSPZ-vaccinated individuals. This is likely through modulation of immune system activation and systemic cytokines as higher levels of IL-2 and IL17A were observed in HPgV-1 infected individuals. CHMI is safe and well tolerated in HPgV-1 infected individuals. Identification of cell types and mechanisms of both silent and productive infection in individuals will help to unravel the biology of this widely present but largely under-researched virus.
Assuntos
Coinfecção/imunologia , Infecções por Flaviviridae/imunologia , Vacinas Antimaláricas/imunologia , Malária Falciparum/prevenção & controle , Esporozoítos/imunologia , Adolescente , Adulto , Estudos de Coortes , Coinfecção/complicações , Coinfecção/parasitologia , Coinfecção/virologia , Feminino , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/complicações , Infecções por Flaviviridae/epidemiologia , Guiné , Humanos , Vacinas Antimaláricas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pegivirus/genética , Pegivirus/imunologia , Plasmodium falciparum/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Tanzânia , Vacinação , Potência de Vacina , Adulto JovemRESUMO
Most human pegivirus 2 (HPgV-2) infections are associated with past or current hepatitis C virus (HCV) infection. HPgV-2 is thought to be a bloodborne virus: higher prevalence of active infection has been found in populations with a history of parenteral exposure to viruses. We evaluated longitudinally collected blood samples obtained from injection drug users (IDUs) for active and resolved HPgV-2 infections using a combination of HPgV-2-specific molecular and serologic tests. We found evidence of HPgV-2 infection in 11.2% (22/197) of past or current HCV-infected IDUs, compared with 1.9% (4/205) of an HCV-negative IDU population. Testing of available longitudinal blood samples from HPgV-2-positive participants identified 5 with chronic infection (>6 months viremia in >3 timepoints); 2 were identified among the HCV-positive IDUs and 3 among the HCV-negative IDUs. Our findings indicate that HPgV-2 can establish chronic infection and replicate in the absence of HCV.
Assuntos
Usuários de Drogas , Infecções por Flaviviridae/epidemiologia , Hepatite C , Pegivirus/isolamento & purificação , Adolescente , Adulto , California/epidemiologia , Coinfecção , Feminino , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/virologia , Humanos , Estudos Longitudinais , Masculino , Prevalência , Assunção de Riscos , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: In racehorses, serum gamma-glutamyltransferase (GGT) activity is positively correlated with cumulative days in training and, when ≥100 IU/L, has been associated with poor performance. The prevalence of increased GGT activity in North American Thoroughbreds and its aetiopathogenesis are unknown. Four emerging viruses, pegivirus E (PgV E; equine pegivirus), hepacivirus A (HcV A; equine hepacivirus), pegivirus D (PgV D; Theiler's disease virus), and equine parvovirus-hepatitis (EqPV-H) have been identified in horses with clinical and subclinical hepatopathy. Available prevalence data indicate these viruses may commonly infect racehorses and contribute to increased liver enzyme activity in this population. OBJECTIVES: To investigate the association between viral infection and increased liver enzyme activity in racing Thoroughbreds. STUDY DESIGN: Cross-sectional study. METHODS: Prerace blood samples were collected from 802 Thoroughbreds and tested for GGT and sorbitol dehydrogenase (SDH) activity, and the presence of PgV E, HcV A, PgV D and EqPV-H nucleic acid. RESULTS: Increased SDH and/or GGT were detected in 56.2% of the 802 serum samples. The infection prevalence and relative risk (RR) of having concurrently increased liver enzyme activity were: PgV E = 18.2% (RR = 0.820, 95% CI = 0.662-0.978, P = 0.03), HcV A = 2.5% (RR = 1.132, 95% CI = 0.719-1.466, P = 0.6), PgV D = 0.5% (RR = 0.875, 95% CI = 0.165-1.598, P>0.9), EqPV-H = 2.9% (RR = 0.916, 95% CI = 0.564-1.266, P = 0.7). MAIN LIMITATIONS: Longitudinal samples were not tested. CONCLUSIONS: While viral infection was common among Thoroughbreds in this study, infection did not explain the high prevalence of increased liver enzyme activity. In fact, PgV E infection was associated with a reduced risk of having increased liver enzyme activity, indicating PgV E is unlikely to be a cause of hepatitis in horses. Importantly, like GGT, increased SDH activity was highly prevalent in this study, and provides additional evidence that hepatocellular injury was occurring in these horses.
Assuntos
Infecções por Flaviviridae/veterinária , Doenças dos Cavalos/virologia , L-Iditol 2-Desidrogenase/metabolismo , Infecções por Parvoviridae/veterinária , gama-Glutamiltransferase/metabolismo , Animais , Biomarcadores , Doenças Transmissíveis Emergentes/veterinária , Doenças Transmissíveis Emergentes/virologia , Flaviviridae/classificação , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/virologia , Regulação Enzimológica da Expressão Gênica , Cavalos , L-Iditol 2-Desidrogenase/genética , Fígado/enzimologia , Infecções por Parvoviridae/virologia , Parvovirinae , gama-Glutamiltransferase/genéticaRESUMO
The prevalence of chronic hepatitis C virus (HCV) and the presence of human pegivirus 2 (HPgV-2) have not been examined in Cameroon, although HCV has been associated with HPgV-2 infections previously. Herein we aimed to characterize the burden and genetic diversity of HCV and the presence of HPgV-2 in Cameroon. Retrospective plasma specimens collected from N = 12 369 consenting subjects in South Cameroon from 2013 to 2016 were included in the study. The majority (97.1%) of participants were patients seeking health care. All specimens were screened for HCV using the Abbott RealTime HCV viral load assay and positive specimens with remaining volume were also screened for HPgV-2 antibodies on the Abbott ARCHITECT instrument, followed by molecular characterization. Overall, HCV RNA was detected in 305 (2.47%; 95% CI: 2.21%-2.75%) specimens. Notably, the prevalence of HCV RNA was 9.09% amongst participants over age 40 and 3.81% amongst males. Phylogenetic classification of N = 103 HCV sequences identified genotypes 1 (19.4%), 2 (15.5%) and 4 (65.1%) within the study cohort. Amongst HCV RNA-positive specimens, N = 28 (10.6%; 95% CI: 7.44%-14.90%) specimens also had detectable HPgV-2 antibodies. Of these, N = 2 viremic HPgV-2 infections were confirmed by sequencing and shared 93-94 median % identity with strains found on other continents. This is the first study to determine the prevalence of chronic HCV in Cameroon, and the discovery of HPgV-2 in this study cohort expands the geography of HPgV-2 to the African continent, indicating a widespread distribution exists.
Assuntos
Anticorpos Antivirais/sangue , Monitoramento Epidemiológico , Infecções por Flaviviridae/epidemiologia , Flaviviridae/isolamento & purificação , Hepatite C Crônica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Camarões/epidemiologia , Criança , Pré-Escolar , Coinfecção/epidemiologia , Coinfecção/virologia , Feminino , Flaviviridae/genética , Infecções por Flaviviridae/sangue , Hepacivirus/genética , Hepatite C Crônica/sangue , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , RNA Viral/sangue , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: Hepatitis G virus (HGV) infection appears to be common in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to investigate the prevalence of HCV/HGV in patients with chronic hepatitis C (CHC) in Pakistan and to look for possible associations with various clinical and histopathological changes in HCV/HGV coinfection and HCV infection. PATIENTS AND METHODS: The present study included 136 patients. Clinical, biochemical, virological and histological findings were compared between patients coinfected with HCV/HGV and patients with HCV alone. RESULTS: Of the 136 patients with CHC, 16 (11.76%) were coinfected with HCV/HGV. The mean age of coinfected patients was lower than in patients with HCV alone. HCV/HGV coinfected patients did not show significant differences in sex, clinical presentation, biochemical markers, and liver fibrosis as compared to those with HCV infection. Only the mean values of platelets count, mean corpuscular hemoglobin (MCH), and MCH concentration markers were significantly different in HCV/HGV coinfected patients as compare to patients with HCV alone. CONCLUSION: It was found that 11.76% of patients with CHC in Pakistan were associated with HCV/HGV coinfection. No significant differences were observed in clinical and histological features except for platelets count, MCH, and MCH concentration markers between HCV and HGV coinfected patients in comparison with HCV-infected patients.
Assuntos
Coinfecção/epidemiologia , Infecções por Flaviviridae/epidemiologia , Vírus GB C/patogenicidade , Hepatite C Crônica/epidemiologia , Hepatite Viral Humana/epidemiologia , Adulto , Coinfecção/sangue , Coinfecção/diagnóstico , Coinfecção/virologia , Índices de Eritrócitos , Feminino , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/diagnóstico , Infecções por Flaviviridae/virologia , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Hepatite Viral Humana/sangue , Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Contagem de Plaquetas , Prevalência , Carga ViralRESUMO
A novel blood-borne virus called the human hepegivirus 1 (HHpgV-1) was recently discovered in hemophilia patients. The present study aimed to investigate the presence of HHpgV-1 in hemophilia patients. A total of 436 serum samples were investigated for the presence of hepatitis C virus (HCV), human pegivirus-1 (HPgV-1), torque teno virus (TTV), and HHpgV-1. Out of the 436 patients, 163 (37.4%), 19 (4.4%), 76 (17.4%), and four (0.9%) patients were positive for HCV, HPgV-1, TTV, and HHpgV-1, respectively. HHpgV-1 patients had a mean viral load of 4.9 ± 0.3 log RNA copies/mL and were co-infected with HCV-1a, HPgV-1, and TTV. Moreover, three HHpgV-1-positive patients exhibited stage F0 liver fibrosis. HCV viral load in HHpgV-1-positive patients was lower than those of HHpgV-1-negative patients. Results also revealed that co-infection of HHpgV-1 with HPgV-1 and HCV may play a protective role in patients with chronic HCV. In conclusion, we detected a low frequency of HHpgV-1 infection in hemophilia patients, and results suggested that HHpgV-1 infection was correlated with the presence of other blood-borne viruses and is likely to also correlate with low HCV viral load and reduced severity of liver disease. Additional studies are required to further investigate the clinical importance of HHpgV-1.
Assuntos
Patógenos Transmitidos pelo Sangue/isolamento & purificação , Coinfecção/epidemiologia , Infecções por Flaviviridae/epidemiologia , Flaviviridae/isolamento & purificação , Hemofilia A/terapia , Hepatite C/epidemiologia , Adulto , Transfusão de Sangue , Coinfecção/sangue , Coinfecção/diagnóstico , Coinfecção/transmissão , Feminino , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/diagnóstico , Infecções por Flaviviridae/transmissão , Hemofilia A/sangue , Hepatite C/sangue , Hepatite C/diagnóstico , Hepatite C/transmissão , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Prevalência , Carga Viral , Adulto JovemRESUMO
We compared the plasma viromes of HIV-infected subjects with low versus high CD4(+) T cell counts from the United States and Uganda by using deep sequencing and detected HIV, hepatitis C virus, hepatitis B virus, GB virus C, anellovirus, and human endogenous retrovirus (HERV) reads. An increase in the proportion of reads for anelloviruses, a family of highly prevalent and genetically diverse human viruses, was seen in subjects with AIDS from both countries. The proportion of endogenous human retrovirus reads was increased in AIDS subjects from Uganda but not the United States. Progression to AIDS is therefore associated with changes in the plasma concentration of commensal viruses.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Contagem de Linfócito CD4 , Infecções por Flaviviridae/etiologia , HIV/patogenicidade , Hepatite Viral Humana/etiologia , Replicação Viral , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/genética , Síndrome da Imunodeficiência Adquirida/virologia , Adulto , Anelloviridae/patogenicidade , DNA Viral/genética , Progressão da Doença , Feminino , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/epidemiologia , Vírus GB C/metabolismo , Vírus GB C/patogenicidade , HIV/metabolismo , Hepatite Viral Humana/sangue , Hepatite Viral Humana/epidemiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Uganda/epidemiologia , Estados Unidos/epidemiologia , Carga Viral , Adulto JovemRESUMO
The main objectives of the design of GB virus C (GBV-C) peptide microarrays are the miniaturisation of antigen-antibody interaction assays, the simultaneous analysis of several peptide sequences and the reduction in the volume of serum required from patients since this always represents a limiting factor in studies to develop new systems for diagnosing human diseases. We herein report the design of a microarray immunoassay based on synthetic peptides derived from the GBV-C E2 protein to evaluate their diagnostic value in detecting anti-E2 antibodies in HIV-1 patients. To this end, peptide microarrays were initially prepared to identify the most relevant epitopes in the GBV-C E2 protein. Thus, 124 peptides composed of 18 amino acids covering the whole E2-protein sequence, with 15 residue overlaps, were spotted in triplicate onto γ-aminopropyl silane-functionalised adsorbent binding slides. The procedure to select the E2 protein epitopes was carried out using serum samples from HIV-1-infected patients. The samples had previously been tested for the presence or absence of GBV-C anti-E2 antibodies by means of the Abbott test. Thus, 11 specific epitopes in the GBV-C E2 protein were identified. Subsequently, peptide antigen microarrays were constructed using the E2 epitopes identified to detect GBV-C anti-E2 antibodies in the serum of HIV-1-infected patients with no known GBV-C co-infection. The 11 peptides selected identified anti-E2 GBV-C antibodies among HIV-1-infected patients, and a reactivity of 47 % was established. The potential antigenic peptides selected could be considered a useful tool for designing a new diagnostic system based on peptide microarrays to determine anti-GBV-C E2 antibodies in the serum of HIV-1-infected patients.
Assuntos
Anticorpos Antivirais , Infecções por Flaviviridae/diagnóstico , Vírus GB C/isolamento & purificação , Infecções por HIV/complicações , Hepatite Viral Humana/diagnóstico , Análise Serial de Proteínas/métodos , Proteínas E2 de Adenovirus , Anticorpos Antivirais/sangue , Coinfecção , Epitopos/química , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/complicações , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , Hepatite Viral Humana/sangue , Hepatite Viral Humana/complicações , Humanos , Imunoensaio/métodos , Proteínas Virais/químicaRESUMO
BACKGROUND & AIMS: Studies have shown that GB virus C (GBV-C) infection leads to reduced liver disease in hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection. Considering that the underlying mechanism(s) are unknown, we aim to identify differential gene and protein expression associated with GBV-C in HCV/HIV co-infection that may be responsible for reduced liver disease. METHODS: Liver, peripheral blood mononuclear cells (PBMCs), and plasma samples were collected from 43 HCV/HIV patients. Plasma was tested for GBV-C RNA by RT-PCR with NS5B gene primers. A microarray was performed on the liver and RT-qPCRs on the liver/PBMC samples. Hepatic protein expression was measured by immunohistochemistry. RESULTS: Sixteen out of 43 patients had GBV-C RNA. GBV-C was associated with reduced hepatic fibrosis (p=0.005) and inflammation (p=0.007). The microarray analysis of the liver samples (n=10) showed down-regulation of genes critical to intra-hepatic T-cell signaling associated with GBV-C. Quantitative RT-PCR of the liver samples (n=13) confirmed the down-regulation of lymphocyte-specific protein tyrosine kinase (LCK) (p=0.02) and docking protein 2 (DOK2) (p=0.04). No differences in the expression levels of these genes were observed in PBMCs (n=22) according to the GBV-C status. The hepatic expression of the LCK protein, measured by immunohistochemistry (n=36), was decreased in CD3-positive T-cells within portal tracts associated with GBV-C (p=0.003). This remained significant in multivariate analysis controlling for hepatic fibrosis and inflammation (p=0.027). No differences were observed in plasma cytokine concentrations (n=25) or ex-vivo peripheral T-cell responses (n=13) versus GBV-C status. CONCLUSIONS: GBV-C infection is associated with down-regulation of critical genes involved in intra-hepatic T-cell signaling in HCV/HIV co-infection. This may be relevant to the pathogenesis of reduced HCV-related liver disease in HIV co-infection.
Assuntos
Regulação para Baixo/genética , Infecções por Flaviviridae/genética , Infecções por Flaviviridae/metabolismo , Vírus GB C/metabolismo , Infecções por HIV/complicações , Hepatite Viral Humana/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Complexo CD3/genética , Complexo CD3/metabolismo , Coinfecção , Citocinas/sangue , Regulação para Baixo/imunologia , Feminino , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/complicações , Vírus GB C/imunologia , Infecções por HIV/imunologia , Hepatite C/complicações , Hepatite C/imunologia , Hepatite C/metabolismo , Hepatite C/patologia , Hepatite Viral Humana/sangue , Hepatite Viral Humana/complicações , Hepatite Viral Humana/genética , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , RNA Viral/sangue , Índice de Gravidade de Doença , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Células Th1/metabolismo , Células Th2/metabolismoRESUMO
BACKGROUND: Anellovirus species Torque teno virus (TTV), Torque teno mini virus (TTMV), and Torque teno midi virus (TTMDV) and flavivirus GBV-C are highly prevalent and genetically diverse chronic human viral infections that have not yet been associated with disease. STUDY DESIGN AND METHODS: To determine if these commensal viruses are transmitted by blood transfusions, we genetically analyzed viral species in cryopreserved samples from blood donors and corresponding pre- and posttransfusion samples from recipients enrolled in the Transfusion-Transmitted Viruses Study cohort. RESULTS: All 24 individuals in 12 donor-recipient pairs were infected with TTV, while 16 were infected with TTMV, 15 with TTMDV, and four with GBV-C. None of the 12 informative cases of TTV transfusion or eight cases of TTMV transfusion, where the donor and recipient viruses could be genetically differentiated, resulted in detectable transmissions in which the donor viruses were detected in the recipient by direct sequencing of the polymerase chain reaction products. Of the five informative cases of TTMDV transfusion, including two cases of transfusion into TTMDV-negative recipients, one case of superinfection was seen with both the recipient and the donor viral variants detected in the transfusion recipient for at least 11 days posttransfusion. Three donor-recipient pairs were informative for GBV-C transmission with only one transfusion into a GBV-C-negative recipient resulting in a transiently detected infection. CONCLUSIONS: Transmission of the common commensal anelloviruses and GBV-C during transfusion was detected in 2 of 12 already infected or uninfected recipients. Underestimation of the true rate of viral transmission may be due to limitations in detecting donor viral variants present as minority variants in the already infected transfusion recipients.
Assuntos
Transfusão de Sangue/estatística & dados numéricos , Infecções por Vírus de DNA , Infecções por Flaviviridae , Vírus GB C/isolamento & purificação , Hepatite Viral Humana , Torque teno virus/isolamento & purificação , Adulto , Doadores de Sangue/estatística & dados numéricos , Preservação de Sangue , Criopreservação , Infecções por Vírus de DNA/sangue , Infecções por Vírus de DNA/epidemiologia , Infecções por Vírus de DNA/transmissão , DNA Viral/sangue , Feminino , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/epidemiologia , Infecções por Flaviviridae/transmissão , Vírus GB C/genética , Variação Genética , Hepatite Viral Humana/sangue , Hepatite Viral Humana/epidemiologia , Hepatite Viral Humana/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Torque teno virus/genética , Reação TransfusionalRESUMO
The use of synthetic peptides of both structural and nonstructural proteins of GB virus C (GBV-C) has been studied for the development of new systems to diagnose infection caused by this virus. In an attempt to increase the antigenicity of linear peptide sequences, chimeric multiple antigenic peptides (MAPs) containing epitopes from E2, NS4, and NS5 GBV-C proteins have been synthesized. The synthetic constructs were evaluated by ELISA to establish whether the epitopes in chimeric branched peptides are more efficiently recognized by the specific antibodies compared to the monomeric linear sequences. Moreover, we have investigated the application of a commercial biosensor instrument for the detection of antibodies against the GBV-C in human serum samples. The results of the immunoassays reported in this work highlight the usefulness of synthetic tetrameric branched peptides containing sequences from envelope and nonstructural GBV-C proteins for the diagnosis of GBV-C infection. The potential clinical value of the MAP(4)(E2-NS5a) for the serodiagnosis of GBV-C infection was demonstrated, thus providing the basis for performing prevalence studies of the infection among the hemodialyzed and hepatitis C virus (HCV)-infected population.
Assuntos
Antígenos Virais/imunologia , Infecções por Flaviviridae/diagnóstico , Infecções por Flaviviridae/virologia , Vírus GB C/imunologia , Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/virologia , Sequência de Aminoácidos , Anticorpos Antivirais/sangue , Antígenos Virais/química , Ensaio de Imunoadsorção Enzimática , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/imunologia , Hepatite Viral Humana/sangue , Hepatite Viral Humana/imunologia , Humanos , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/imunologia , Curva ROC , Diálise Renal , Sensibilidade e Especificidade , Ressonância de Plasmônio de Superfície , Vacinas Sintéticas/química , Vacinas Sintéticas/imunologiaRESUMO
AIM: To investigate the features of various blood-borne virus infections and co-infection in intravenous drug users (IDUs), and to examine the correlation of T lymphocyte subsets with virus co-infection. METHODS: Four hundred and six IDUs without any clinical manifestation of hepatitis and 102 healthy persons were enrolled in this study. HBV-DNA and HCV-RNA were detected by fluorescence quantitative PCR. HBsAg, HBeAg, anti-HBc, anti-HCV, HDV-Ag, anti-HGV, anti-HIV, and HCMV-IgM were assayed by enzyme-linked immunosorbent assay (ELISA) and immunochromatographic tests. The levels of Th1 and Th2 cytokines were measured by ELISA and radioactive immune assay (RIA). The T lymphocyte subpopulation was detected by using fluorescence immunoassay. The similar indices taken from the healthy persons served as controls. RESULTS: The viral infection rate among IDUs was 36.45% for HBV, 69.7% for HCV, 47.3% for HIV, 2.22% for HDV, 1.97% for HGV, and 3.45% for HCMV. The co-infection rate of blood-borne virus was detected in 255 of 406 (62.81%) IDUs. More than 80% (161/192) of subjects infected with HIV were co-infected with the other viruses, such as HBV, HCV. In contrast, among the controls, the infection rate was 17.65% for HBV and 0% for the other viruses. Our investigation showed that there was a profound decrease in the proportion of CD4/CD8 and the percentage of CD3 and CD4, but not in the percentage of CD8. The levels of PHA-induced cytokines (IFN-gamma and IL-4) and serum IL-2 were obviously decreased in IDUs. On the other hand, the level of serum IL-4 was increased. The level of IFN-gamma and the percentage of CD4 were continuously decreased when the IDUs were infected with HIV or HIV co-infection. IDUs with HIV and HBV co-infection was 15.1% (29/192). Of those 29 IDU with HIV and HBV co-infection, 51.72% (15/29) and 37.93% (11/29) were HBV-DNA-positive and HBeAg-positive, respectively. But, among IDUs without HIV infection, only 1.68% (2/119) of cases were HBV-DNA-positive. CONCLUSION: HCV, HBV and HIV infections are common in this population of IDU, leading to a high incidence of impaired Th1 cytokine levels and CD4 lymphocyte. IDUs with HIV and HBV/HCV co-infection have lower expression of Th1 cytokine with enhancement of the Th2 response. HIV may be causing HBV replication by decreasing Th1 function.
Assuntos
Infecções por Flaviviridae/complicações , Infecções por HIV/complicações , Hepatite B/complicações , Hepatite C/complicações , Hepatite Viral Humana/complicações , Abuso de Substâncias por Via Intravenosa/complicações , Subpopulações de Linfócitos T , Adolescente , Adulto , Anticorpos Antivirais/análise , Linfócitos T CD4-Positivos/patologia , Estudos de Casos e Controles , DNA Viral/análise , Feminino , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/imunologia , Vírus GB C/genética , Vírus GB C/imunologia , Infecções por HIV/sangue , Infecções por HIV/imunologia , HIV-1/genética , HIV-1/imunologia , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite B/sangue , Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite C/sangue , Hepatite C/imunologia , Hepatite Viral Humana/sangue , Hepatite Viral Humana/imunologia , Humanos , Interleucina-2/sangue , Interleucina-4/sangue , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Abuso de Substâncias por Via Intravenosa/sangue , Abuso de Substâncias por Via Intravenosa/imunologiaRESUMO
Several reports have documented a better prognosis for HIV-1-infected patients co-infected with GBV-C, while other reports have contradicted such findings with the result that this issue remains controversial. We attempted to clarify the complicated status of the effect of GBV-C co-infection on HIV-1-infected patients. GBV-C RNA was detected in 37 samples in 182 HIV-1-infected patients (20.3%) using RT/nested PCR. Of these, 3 were determined to be GBV-C genotype 1, 12 were genotype 2, and the remaining 22 were genotype 3. The GBV-C viral load quantified by real-time PCR ranged from 7.8x10(3) to 3.3x10(6) copies/ml. Weakly negative correlation was observed between GBV-C viral load and HIV-1 viral load in 19 HAART-naïve patients, indicating that a higher GBV-C viral load is associated with a greater suppression of HIV-1 replication. A previously published in vitro study suggested that GBV-C infection would induce up-regulation of RANTES, leading to suppression of HIV-1 replication. However, in our present study, the blood RANTES level was significantly lower in the GBV-C co-infected group than in the uninfected group (190-9,959 vs. 264-31,038 pg/ml, P=0.004). Our results suggested that a suppression of HIV-1 replication by GBV-C co-infection is not mediated by up-regulated RANTES, and thus call for another as yet unknown factor.
Assuntos
Infecções por Flaviviridae/virologia , Vírus GB C/fisiologia , Infecções por HIV/virologia , HIV-1/fisiologia , Contagem de Linfócito CD4 , Quimiocina CCL5/sangue , Feminino , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/imunologia , Vírus GB C/genética , Genótipo , Infecções por HIV/sangue , Infecções por HIV/imunologia , Humanos , Masculino , RNA Viral/química , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Carga Viral , Replicação ViralRESUMO
Hepatitis G viral (HGV) infection among northeastern Thai blood donors was determined by the nested RT-PCR technique. HGV RNA was amplified by the degenerated helicase primers for a product of the expected size of 83 base pairs were used in this study. Serum samples from 322 of three different categories of northeastern Thai blood donors were included in this study. There were 104 HBsAg and Anti-HCV seronegative blood donors (control group), 100 samples of HBs Ag seropositive blood donors (HBV infected group) and 118 serum samples from anti-HCV seropositive blood donors (HCV infected group). The results demonstrated that HGV RNA was not detected in the control group but was found in 10 individuals (10%) in the HBV infected group and 13 (11%) in the anti-HCV positive blood donors. The prevalences of HGV in both seropositive groups were significantly different from the control group (p = 0.001). HGV co-infection is highly prevalent among northeastern Thai blood donors who are infected with HBV or HCV. The results also reveal that blood donors seronegative for HCV and HBV are a low risk group for HGV infection.
Assuntos
Infecções por Flaviviridae/epidemiologia , Vírus GB C/isolamento & purificação , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Hepatite Viral Humana/epidemiologia , RNA Viral/análise , Doadores de Sangue , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/complicações , Amplificação de Genes , Hepacivirus/isolamento & purificação , Hepatite B/sangue , Hepatite B/complicações , Vírus da Hepatite B/isolamento & purificação , Hepatite C/sangue , Hepatite C/complicações , Hepatite Viral Humana/sangue , Hepatite Viral Humana/complicações , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Tailândia/epidemiologiaRESUMO
201 HIV infected and 200 non HIV infected patients have been observed to detect antibodies to virus hepatitis G. It was established that IgG antibodies are detected more often in HIV infected than in non-HIV-infected persons (24,9% of cases). The highest number of hepatitis G-infected patients is observed among HIV patients at before-HIV clinically apparent stage and HIV clinical stage as well as in patients infected by HIV virus during parenteral infusion.
Assuntos
Infecções por Flaviviridae , Vírus GB C/isolamento & purificação , Infecções por HIV , Anticorpos Anti-Hepatite/sangue , Antígenos de Hepatite/imunologia , Hepatite Viral Humana , Imunoglobulina G/imunologia , Adulto , Idoso , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/complicações , Infecções por Flaviviridae/epidemiologia , Vírus GB C/imunologia , Infecções por HIV/sangue , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Anticorpos Anti-Hepatite/imunologia , Hepatite Viral Humana/sangue , Hepatite Viral Humana/complicações , Hepatite Viral Humana/epidemiologia , Humanos , Pessoa de Meia-IdadeRESUMO
In this work, new putative epitopes located in nonstructural proteins of GBV-C/HGV were synthesized using solid-phase chemistry for their use in immunoassays. The antigens were obtained in linear, chimeric and cyclic forms with the main aim of improving the sensitivity of the enzyme immunoassays. Our results showed, on one hand, that the combination of different antigens seems to be necessary to ensure good sensitivity and more specificity and, on the other hand, that cyclic compounds show higher ability to recognize anti-GBV-C/HGV antibodies than its parent peptide. Furthermore, CD and FTIR have been used in conjunction to characterize the conformational changes therein with synthetic constructs that could explain their different antigenicity.
Assuntos
Epitopos/imunologia , Infecções por Flaviviridae/imunologia , Vírus GB C/imunologia , Peptídeos Cíclicos/imunologia , Proteínas Recombinantes de Fusão/imunologia , Proteínas não Estruturais Virais/imunologia , Sequência de Aminoácidos , Proteínas de Transporte/química , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Dicroísmo Circular , Ensaio de Imunoadsorção Enzimática , Epitopos/química , Epitopos/genética , Infecções por Flaviviridae/sangue , Infecções por Flaviviridae/diagnóstico , Vírus GB C/química , Técnicas Imunoenzimáticas , Peptídeos e Proteínas de Sinalização Intracelular , Dados de Sequência Molecular , Peptídeos Cíclicos/análise , Peptídeos Cíclicos/síntese química , Estrutura Secundária de Proteína , Proteínas Recombinantes de Fusão/análise , Proteínas Recombinantes de Fusão/síntese química , Sensibilidade e Especificidade , Alinhamento de Sequência , Espectroscopia de Infravermelho com Transformada de Fourier , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/imunologiaRESUMO
The levels of soluble CD38 (sCD38), CD50 (sCD50), and CD95 (sCD95) antigens and HLA class I (sHLA-I) were determined in the serum samples from persons infected with hepatitis G virus (HGV). HGV monoinfection was accompanied by a rise in the serum content of sCD38, sCD50, and sCD95 antigens. The serum presence of HGV RNA and anti-E2 HGV antibodies was characterized by the normal content of sCD38 and sCD95 while the level of sCD50 was elevated and the serum content of sHLA-I was decreased. If the serum contained only anti-E2 HGV antibodies, the level of sCD50 remained increased 4-fold. It is suggested that the higher adhesion-inhibiting level of sCD50 is a reason of a weak immune response to HGV and hence of a long HGV persistence in the body.
Assuntos
Antígenos CD/sangue , Moléculas de Adesão Celular/sangue , Infecções por Flaviviridae/sangue , Vírus GB C , Antígenos HLA/sangue , Hepatite Viral Humana/sangue , Receptor fas/sangue , Infecções por Flaviviridae/virologia , Vírus GB C/genética , Vírus GB C/imunologia , Vírus GB C/isolamento & purificação , Anticorpos Anti-Hepatite/sangue , Hepatite Viral Humana/virologia , RNA Viral/sangue , Solubilidade , Proteínas do Envelope Viral/imunologiaRESUMO
The hepatitis G virus (HGV) or GB virus C (GBV-C) was discovered in 1995 as a putative agent of post-transfusion, non-A-E hepatitis. The present study was carried out with the aim to find the prevalence of this virus among various subject groups at risk for parenteral transmission as well as in healthy control subjects both individually and along with other parenterally transmitted hepatitis viruses. Of the 402 subjects tested, 6.22% were positive for the HBsAg surface antigen, 7.21% were positive for HCV RNA while only 2.24% were seen to be carriers of the HGV/GBV-C RNA. All the HGV/GBV-C positive cases were either multi-transfused thalassaemic subjects or hemodialysis patients. None of the healthy control subjects showed presence of the virus. Seven of the HGV/GBV-C positive subjects showed co-infection with one or more additional virological markers. Also, of the 9 HGV/GBV-C positive subjects, 5 showed elevated ALT levels while 4 showed elevated alkaline phosphatase levels. Overall our findings seem to indicate that HGV infections generally are asymptomatic, transient and self-limiting and the virus does not seem to show a very high prevalence among the Indian population.
Assuntos
Doadores de Sangue , Infecções por Flaviviridae/epidemiologia , Infecções por Flaviviridae/transmissão , Vírus GB C/metabolismo , Antígenos de Superfície da Hepatite B/química , Hepatite Viral Humana/epidemiologia , Hepatite Viral Humana/transmissão , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Criança , Pré-Escolar , Estudos de Coortes , DNA Complementar/metabolismo , Feminino , Infecções por Flaviviridae/sangue , Hepacivirus/genética , Hepatite Viral Humana/sangue , Humanos , Índia , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA/metabolismo , RNA Viral/genética , Diálise Renal , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Risco , Talassemia/terapiaRESUMO
OBJECTIVE: To study the prevalence of GBV-C-RNA in sera of HIV-infected patients and determine whether differences in immunological condition and hepatic disease exist between GBV-C positive and negative patients. METHODS: The presence of GBV-C-RNA was determined in sera of 222 HIV-positive patients by semi-automated RT-PCR. A comparison of GBV-C-RNA positive and negative patients was made by studying a series of clinical and analytical parameters. This same comparison was made in particular between those coinfected with HCV and GBV-C and those who only presented GBV-C. RESULTS: Prevalence of GBV-C-RNA was 28.8%. The most frequent hepatotropic virus was HCV, appearing in 71.6% of cases. Coinfection with HCV and HGV was present in 17% and 8.6% only had GBV-C. Patients positive for GBV-C-RNA showed clinical and analytical characteristics similar to those found in GBV-C-RNA negative patients. Among the HCV-GBV-C coinfected and those presenting HGV as the only virus it was observed that the coinfected group presented alterations in transaminases and predominance of parenteral transmission as a risk factor for HIV, whereas the GBV-C group presented normal transaminases and predominance of sexual transmission. No differences were perceived in mean CD4 and HIV-RNA values in both groups. CONCLUSIONS: Being positive for GBV-C in HIV-positive patients does not influence the presence of hepatic disease that in these patients is frequently accompanied by coinfection with other hepatotropic viruses. Moreover, it does not seem to influence the viremia of the HIV nor the CD4 cell counts.