Epidemiologia e caracterização molecular de Pegivirus humano tipo 1 (HPgV-1) em indivíduos coinfectados pelos vírus da hepatite C (HCV) e/ou vírus da imunodeficiência humana (HIV) / Epidemiology and molecular characterization of human Pegivirus type 1 (HPgV-1) in individuals co-infected with hepatitis C virus (HCV) and / or human immunodeficiency virus (HIV)

O Pegivirus humano 1 (HPgV-1) é um vírus de RNA de fita simples de polaridade positiva membro da família Flaviviridae, e que possui similaridade genômica com o vírus da hepatite C (HCV). No entanto, diferentemente do HCV, o HPgV-1 é linfotrópico e estabelece uma infecção subclínica. Vários estudos relataram que a infecção pelo HPgV-1 está associada à progressão tardia da doença pelo HIV, com indivíduos infectados demonstrando maiores contagens de células TCD4+, menor carga viral do HIV, uma progressão mais lenta para AIDS e, consequentemente, uma expectativa de vida prolongada. Em pacientes com coinfecção crônica por HCV e HIV, o RNA do HPgV-1 foi associado a níveis significativamente mais baixos de ALT e AST e a uma melhora na sobrevida livre de cirrose, sugerindo um efeito benéfico da infecção pelo HPgV-1 em ambas as infecções. Para a melhor compreensão do impacto do HPgV-1 nas co-infecções, se faz necessário conhecer as características epidemiológicas desse vírus. O objetivo deste estudo foi determinar a prevalência e distribuição genotípica do HPgV-1 em doadores de sangue e pacientes HCV e HIV positivos atendidos em um hospital no Rio de Janeiro entre os anos de 2017 a 2018.

Um ensaio de RT-PCR para amplificação específica da região 5'UTR do genoma viral foi realizado em 236 amostras de soro, sendo 56 amostras de coinfecção HCV/HIV, 60 de HCV mono-infectadas, 60 de HIV mono-infectadas e 60 de doadores de sangue. Todas as amostras positivas foram submetidas ao seqüenciamento direto do genoma viral para genotipagem e caracterização molecular. A prevalência geral de HPgV-1 foi de 15,7% (37/236). Maiores frequências de HPgV-1 foram encontradas no grupo de indivíduos com HIV 28,3% (17/60), seguido pelos grupos de indivíduos co-infectados com HCV/HIV (14,3%), doadores de sangue (11,6%) e em co-infecção com HCV (8,3%). A análise filogenética revelou a presença dos genótipos 2a (22,8%), 2b (57,1%), 3 (8,5%) e 1 (8,5%) de HPgV-1. Este é o primeiro estudo que caracteriza a infecção pelo HPgV-1 em pacientes com HCV e HCV/HIV na cidade do Rio de Janeiro e que visa contribuir com maiores informações sobre características epidemiológicas e clínicas do HPgV-1 no curso natural da infecções pelo HCV e/ou HIV. (AU)

Insect microbiomes and insect- specific viruses a new key for understanding the arboviruses diseases? / ¿Los microbiomas de insectos y los virus específicos de insectos son una nueva clave para entender las enfermedades de los arbovirus?

Abstract The last past two decades, there has been a tremendous expansion in the discovery and description of novel insect- specific viruses (ISVs). This has corresponded with progresses in metagenomic analyses for virus revealing and the increasing attention in insect microbiomes. Plentiful of the new ISVs seem to be members of the family Flaviviridae, genus Flavivirus, and are usual in insect populations in wildlife, with a global geographic circulation.

Pegivirus humano: potencial patogénico y riesgo de desarrollo de linfoma no Hodgkin / Human Pegivirus: pathogenic potential and non-Hodgkin lymphoma development risk

Resumen El pegivirus humano (HPgV) es un virus ARN que fue identificado en el año 1995. Actualmente se encuentra clasificado dentro de la familia Flaviviridae, género Pegivirus, relacionado filogenéticamente con el virus de la hepatitis C (VHC). El HPgV es un virus linfotrópico, con replicación en médula ósea, tejidos linfoides, y en células mononucleares de sangre periférica. Este virus se transmite por vía parenteral y sexual. Según estimaciones realizadas, en el mundo existen alrededor de 750 millones de personas infectadas por este agente. Se ha evidenciado que hasta en 25% de los casos se presenta una infección persistente, y aunque se considera que el HPgV es un virus no patogénico, existen evidencias epidemiológicas que sugieren una relación con el desarrollo de desórdenes linfoproliferativos, particularmente linfoma no Hodgkin (LNH). Algunos estudios han reportado una alta prevalencia de HPgV en pacientes con LNH comparado con donantes de sangre y/o pacientes con enfermedades hematológicas no malignas, lo que se asocia a un incremento en el riesgo relativo para el desarrollo de LNH en personas infectadas. De otra parte, existen estudios epidemiológicos que contradicen esta asociación, por lo que el rol de HPgV en la aparición de desórdenes lifoproliferativos es un tema actual de debate. En el presente manuscrito se discute el potencial patogénico derivado de los mecanismos de infección persistente del HPgV, así como las principales evidencias sobre la relación entre el HPgV y el riesgo de desarrollo de LNH.

The human pegivirus (HPgV), classified in the Flaviviridae family - Pegivirus genus, is an RNA virus identified in 1995. HPgV is a lymphotrophic virus, with replication sites in bone marrow and lymphoid tissue, as well as in peripheral blood mononuclear cells (PBMCs). Transmission is through sexual and parenteral routes, and recent estimations suggest nearly 750 million people are infected with HPgV worldwide. Almost 25% of infected individuals can develop persistent infection. Until now, HPgV has been considered a non-pathogenic virus; however, epidemiological studies suggest a potential role in lymphoproliferative diseases, particularly in the development of non-Hodgkin lymphoma (NHL). The evidence of this is controversial and the role of HPgV in lymphomagenesis has not yet been demonstrated. Several studies report a high prevalence of HPgV infection in patients with NHL compared to controls and patients with other hematological diseases. Therefore, analytic studies show that HPgV could be related to an increased risk of NHL development. Conversely, other studies indicate no association between HPgV and NHL, so the role of HPgV in lymphomagenesis is not clear. This review summarizes the main findings related to HPgV's pathogenic potential and association with NHL.

Interacción entre el virus de la inmunodeficiencia humana y el virus GB tipo-C durante el estado de co-infección / Interaction between HIV-1 and GB virus type-C during coinfection status

The human immunodeficiency virus (HIV) infection is one of the most important problems in public health. It is estimated that 3 3 million people are infected around the world. HIV and GBV-C share the same transmission route, being frequent the co-infection. Since both viruses replicate in CD4+ lymphocytes, recent studies have described an interaction. Decreasing of HIV viral load and higher CD4 counts have been observed in co-infected patients, leading a better clinical outcome. Nevertheless, some epidemiological studies have shown contradictory results. Additionally, in vitro models report inhibition of HIV by E1, E2, NS3 and NS5A GBV-C proteins, resulting in a decreasing of p24 antigen. This review summarizes the principal findings about co-infection and mechanisms that have been proposed for HIV-1 inhibition.

La infección por el virus de la inmunodeficiencia humana (VIH) continúa siendo uno de los principales problemas en salud pública; se estima que existen actualmente más de 33 millones de personas infectadas en el mundo. El VIH y el virus GB tipo C (GBV-C) comparten la misma vía de transmisión, por lo que es frecuente encontrar individuos co-infectados. Estudios recientes han descrito un efecto inhibitorio asociado a disminución en la carga viral de VIH, altos recuentos de CD4 y mayor tiempo de sobrevida en pacientes co-infectados, resultando en un mejor pronóstico y menor progreso a SIDA; adicionalmente, estudios in vitro indican que las proteínas virales E1, E2, NS3 y NS5A del GBV-C estarían implicadas en la inhibición del VIH-1. En el presente artículo se revisan los principales aspectos de la co-infección, y se describen los mecanismos propuestos para la inhibición de la replicación del VIH-1 mediada por las proteínas virales del GBV-C.

Actualización en el tratamiento de la Hepatitis C / An update in the therapy of Hepatitis C

La hepatitis C es una enfermedad infecto contagiosa causada por 6 genotipos del virus del mismo nombre que puede responder de manera distinta al tratamiento. El virus de 30 a 38 nm de tamaño, posee una envoltura y una sola cadena de ARN (+), pertenece a la familia Flaviviridae. La hepatitis C constituye un grave problema de salud pública se calcula que las tasas de infectados en la mayoría de los países se encuentra entre el 1,5 y el 3 %, siendo su tratamiento complejo.

Hepatitis C is a communicable disease caused by 6 genotypes of the hepatitis C virus, and this condition may have a variable response to therapy. Viral particles are 30-38 nm long, they have an envelope and single-stranded RNA. The virus belongs to the Flaviviridae family. Hepatitis C is a severe public health problem. It has been estimated that the rate of infected persons in most of the countries lies between 1,5 to 3 per cent, and its therapy is quite complex.

Analysis of GB virus C infection among HIV-HCV coinfected patients / Análise da infecção pelo vírus GB-C em pacientes com coinfecção VIH-VHC

The aim of this study was to evaluate the effect of GB virus C on laboratory markers and histological parameters among HIV-seropositive patients coinfected with HCV. Lower degrees of hepatic lesions were observed in the triple-infected patients, in comparison with HIV-HCV coinfected patients who were negative for GBV-C RNA.

O objetivo do estudo foi avaliar o efeito da infecção pelo vírus GB-C em marcadores laboratoriais e parâmetros histológicos em pacientes HIV soropositivos coinfectados com VHC. Menor grau de lesão hepática foi observado nos pacientes com tripla infecção em comparação aos pacientes coinfectados com VIH-VHC negativos para GBV-C RNA.

Prevalência e fatores associados à infecção pelo vírus da diarréia viralbovina na região Sul do Rio Grande do Sul / Prevalence and factors associated with bovine viral diarrhea virus infection in South of Rio Grande do Sul

O presente estudo teve como objetivo estimar a prevalência e determinar os principais fatores associadosà infecção pelo vírus da diarréia viral bovina (BVDV) no rebanho bovino dos municípios de Santa Vitóriado Palmar e Chuí, na região sul do estado do Rio Grande do Sul. Amostras de soro foram submetidas àprova de soroneutralização e, em cada propriedade avaliada, aplicou-se um questionário epidemiológicopara investigar fatores que poderiam estar associados à infecção. As amostras de soro foram coletadasem 85 propriedades, cujos animais apresentavam ou não sinais clínicos de infecção pelo BVDV. Das1.734 amostras de soro analisadas, 1.150 (66,32%) foram positivas com a detecção de bovinossorologicamente positivos em 70 (82,35%) propriedades. Dentre os fatores avaliados, exploração mista,criação extensiva, realização de ordenha mecânica, uso de inseminação artificial ou de inseminaçãoartificial associada à monta natural, uso de piquete de parição e ausência de assistência veterinária,apresentaram significância estatística (P<0,05) associada à soropositividade. Os resultados obtidosdemonstram a expressiva disseminação do BVDV no rebanho bovino dessa região do Rio Grande do Sul.

This study was performed in order to estimate the prevalence of bovine viral diarrhea virus (BVDV), andto determine the main factors related to the prevalence of the infection in cattle of Santa Vitória do Palmarand Chuí counties, in Rio Grande do Sul State. Sera were submitted to the serum neutralization test andan epidemiological questionnaire was filled out in each herd to investigate variables that could beassociated with this infection. The sera samples were collected in 85 farms, with or without clinical signsof BVDV infection. From 1.734 serum samples examined, 1.150 (66.32%) in 70 (82.35%) herds were positive.Variables that were identified as risk factors to seropositivity were mixed (dairy and beef) herds, extensive production, use of mechanical milking, use of artificial insemination or artificial insemination associated with natural service, use of the maternity unit at calving and absence of veterinarian assistance (P<0.05).The results demonstrate the expressive dissemination of the BVDV in cattle of this region in Rio Grande do Sul

Cáncer de hígado y virus de las hepatitis B y C / Liver cancer and hepatitis B and C virus

Uno de los tumores hepáticos mas frecuentes, y de mayor malignidad es el carcinoma hepatocelular (CHC), el mismo que se encuentra estrechamente relacionado con el virus de la hepatitis B y C. Según estudios realizados, se ha demostrado que hay mayor incidencia de CHC en los portadores crónicos del HBsAg, aunque el mecanismo por el cual el virus de la hepatitis B puede desarrollar el CHC no está totalmente esclarecido; no obstante existe una relación directa con los procesos necroinflamatorios crónicos que el virus puede inducir. Es importante señalar también la incidencia del CHC por VHC ya que según estudios realizados utilizando sistemas ELISA, se demostró la presencia y replicación del virus en tejido hepático tumoral, confirmando de esta forma la asociación causal entre la infección por el VHC y CHC.En ensayos realizados en Taiwan e Italia, se observó que en pacientes en los que se detectaron simultáneamente ambos marcadores virales (HBsAg y el antiVHC), el riesgo de desarrollar CHC fue mayor, en comparación a aquellos que presentaron en forma aislada, la infección por uno de los 2 virus.Los mecanismos por los cuales la presencia de los virus de las hepatitis B y C promueven el desarrollo del CHC, no esta esclarecido totalmente; pero en la revisión de la literatura se plantean hipótesis importantes en cuanto al efecto oncogénico directo que pueden tener, así como los mecanismos indirectos que actúan por un incremento en la tasa de recambio de hepatocitos o por la producción de radicales libres.Estas son las razones por las cuales la Agencia Internacional para la investigación sobre el cáncer de la OMS se ha pronunciado sobre considerarlos, en especial al VHC, como agente carcinógeno en humanos.

One of the most common liver tumors, and of greatest malignancy, is the hepatocellular carcinoma (HCC), which is closely linked to Hepatitis B and C viruses.According to some studies, it has been demonstrated that the incidence of HC is highest among chronic carriers of HBAgs, although the mechanism by which the virus can lead to HCC is not well identified, thus there is a direct relationship among the chronic necroinflammatory processes that this virus can induce.It is also important to mention the incidence of HCC due to HCV, because there is studies in which the presence and replication of the virus in a normal liver tissue has been demonstrated by Elisa procedures, therefore confirming the causative association among virus infection and HCC.In some trials conducted in Taiwan and Italy, it was observed that the patients in which both viral markers (HBAgs and antiHCV) were detected simmoultaneously, the risk of developing HCC was higher, in comparison to those who presented isolated infection by one of the 2 viruses.The mechanisms by which the presence of both viruses, hepatitis B and C can promote the development of HCC is not totally determined, but the review of the literature suggests important hypothesis concerning a direct oncogenic effect, as well as indirect mechanisms, involving an increase in the exchange rate of hepatocites or the production of free radicals.These are the reasons for which the International Agency for the investigation of cancer of the WHO has pronounced into consideration, specially the HCV as a carcinogenic agent in humans.

GBV-C/HGV and HIV-1 coinfection

An interesting interaction pattern has been found between HIV-1 and GBV-C/HGV, resulting in protection against progression to AIDS. The mechanisms involved in this interaction remain to be clarified. We examined the current knowledge concerning this coinfection and developed hypotheses to explain its effects. A better understanding of this interaction could result in new concepts, which may lead to new strategies to control HIV-1 replication and progression to AIDS.

GB virus C/hepatitis G virus infection in dialysis patients and kidney transplant recipients in central Brazil

In order to investigate the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) infection in dialysis patients and kidney transplant recipients in Central Brazil and also to analyze the virus genotypes distribution, a total of 123 patients including 98 on hemodialysis, 13 on continuous ambulatory peritoneal dialysis treatment, and 12 who received kidney transplantation were interviewed in one unit of dialysis treatment in Goiânia city. Blood samples were collected and serum samples tested for GBV-C/HGV RNA by polymerase chain reaction. Genotypes were determined by restriction fragment length polymorphism (RFLP) analysis. Eighteen samples were GBV-C/HGV RNA-positive, resulting in an overall prevalence of 14.6 percent (95 percent CI: 9.2-21.7). A high positivity for GBV-C/HGV RNA was observed in patients who had received kidney transplant (16.7 percent), followed by those on hemodialysis (15.3 percent), and peritoneal dialysis (7.7 percent). RFLP analysis revealed the presence of genotypes 1, 2, and 3 of GBV-C/HGV; more precisely, 9 (50 percent) samples were found belonging to the 2b subtype, 4 (22 percent) to the 2a subtype, 3 (17 percent) to genotype 1, and 2 (11 percent) to genotype 3. The present data indicate an intermediate prevalence of GBV-C/HGV infection among dialysis patients and kidney transplant recipients in Central Brazil. Genotype 2 (subtype 2b) seems to be the most prevalent GBV-C/HGV genotype in our region.

High prevalence of GB Virus C/Hepatitis G Virus RNA among Brazilian blood donors

The aim of this study was to investigate the presence of the Hepatitis G Virus on a population of blood donors from São Paulo, Brazil and to evaluate its association to sociodemographic variables. Two RT-PCR systems targeting the putative 5'NCR and NS3 regions were employed and the former has shown a higher sensitivity. The observed prevalence of HGV-RNA on 545 blood donors was 9.7 percent (CI 95 percent 7.4;12.5). Statistical analysis depicted an association with race/ethnicity, black and mulatto donors being more frequently infected; and also with years of education, less educated donors presenting higher prevalences. No association was observed with other sociodemographic parameters as age, gender, place of birth and of residence. DNA sequencing of nine randomly chosen isolates demonstrated the presence of genotypes 1, 2 and 3 among our population but clustering of these Brazilian isolates was not detected upon phylogenetic analysis

Prevalence and genotypes of GB Virus C/Hepatitis G virus among blood donors in Central Brazil

A survey was conducted in a blood donor population of Central Brazil aiming to investigate the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) infection and also to analyze the virus genotypes distribution. A total of 241 voluntary blood donors were interviewed at the State Blood Bank in Goiânia, State of Goiás, Brazil. Blood samples were collected and serum samples tested for GBV-C/HGV RNA by polymerase chain reaction. Genotypes were determined by restriction fragment length polymorphism (RFLP) analysis. Seventeen samples were GBV-C/HGV RNA-positive, resulting in a prevalence of 7.1 percent (95 percent CI: 4.2-11.1). A significant trend of GBV-C/HGV RNA positivity in relation to age was observed, with the highest prevalence in donors between 29-39 years old. Ten infected individuals were characterized by reporting parenteral (30 percent), sexual (18 percent), both (6 percent) and intrafamiliar (6 percent) transmission. However, 7 (40 percent) GBV-C/HGV RNA-positive donors did not mention any potential transmission route. RFLP analysis revealed the presence of genotypes 1 and 2 of GBV-C/HGV; more precisely, 10 (58.9 percent) samples were found belonging to the 2b subtype, 4 (23.5 percent) to the 2a subtype, and 3 (17.6 percent) to genotype 1. The present data indicate an intermediate endemicity of GBV-C/HGV infection among this blood donor population, and a predominant circulation of genotype 2 (subtype 2b) in Central Brazil

Liver histology in co-infection of hepatitis C Virus (HCV) and hepatitis G virus (HGV)

As little is known about liver histology in the co-infection of hepatitis C virus (HCV) and hepatitis G virus (HGV), HGV RNA was investigated in 46 blood donors with hepatitis C, 22 of them with liver biopsy: co-infection HCV / HGV (n = 6) and HCV isolated infection (n = 16). Besides staging and grading of inflammation at portal, peri-portal and lobular areas (Brazilian Consensus), the fibrosis progression index was also calculated. All patients had no symptoms or signs of liver disease and prevalence of HGV / HCV co-infection was 15.2 percent. Most patients had mild liver disease and fibrosis progression index, calculated only in patients with known duration of infection, was 0.110 for co-infection and 0.130 for isolated HCV infection, characterizing these patients as "slow fibrosers". No statistical differences could be found between the groups, although a lesser degree of inflammation was always present in co-infection. In conclusion co-infection HCV / HGV does not induce a more aggressive liver disease, supporting the hypothesis that HGV is not pathogenic

Prevalencia de infección por virus de hepatitis G en una cohorte de pacientes hemofílicos HIV+ / [Prevalence of hepatitis G virus infection in a cohort of hemophilic HIV positive patients]

We analysed the prevalence of hepatitis G virus (HGV) infection in HCV+/HIV+ hemophilic patients determining HGV viremia in plasma by polymerase chain reaction (PCR). The overall prevalence of HGV infection was 13.51

. Viremia by HGV was more frequent in younger patients. Two subgroups of patients were considered taking into account prognosis of HIV disease progression. The prevalence of HGV infection was significantly higher in those with better prognosis and low risk of evolution to AIDS. The results suggest that HGV infection may slow disease progression, directly or indirectly.

Virus da hepatite G ou vírus Gb-C: um novo agente associado à hepatites humanas / Hepatitis G virus or GB virus C: a novel agent associated with human hepatitis

Um novo agente envolvido com hepatites não A-E, denominado como vírus da hepatite G ou vírus GB-C (HGV/GBV-C) foi recentemente descoberto. Este vírus pertence à família Flaviviridae, formando um grupo distinto junto com o HCV, GBV-A e GBV-B. A transmissão deste vírus é feita principalmente por transfusões sanguineas, mas também pode ocorrer transmissão vertical, e mesmo horizontal, em comunidades fechadas. Este vírus foi encontrado em casos de hepatites agudas, crônicas e fulminantes em diferentes regiões do mundo, inclusive no Brasil.

Subtipos del virus de la hepatitis C (VHC) y su posible relación con arbovirus de la familia flaviviridae como dengue y fiebre amarilla en el norte y suroriente de Colombia / Hepatitis c virus subtypes and its possible relationship with arboviruses from Flaviviridae family like dengue and yellow fever in the Colombian north and southeast

En personal de salud del ISS de Colombia, se detectaron anticuerpos contral el VHC, por pruebas de segunda y/o tercera generación de Abbot. No todas las muestras que fueron doblemente reactivas por las pruebas de segunda generación, lo fueron también por la tercera. Un problema similar se había encontrado en otro estudio previo. Por esta razón, se decidió reestudiar las muestras doblemente reactivas por Abbott, con las nuevas pruebas desarrolladas por Murex. Esto aclaró en parte la situación, pero las nuevas pruebas no permitieron resolver el problema de los falsos positivos. Por ello se usaron nuevos sueros, positivos para Dengue y encefalitis equina venezolana de la Guajira y la Vega Cundinamarca.

Handbook of zoonoses; section B: viral

Rocio viral encephalitis is an acute severe neurological human disease caused by a Flavivirus which lends its name to the disease

Molecular approach to the development of flavivirus vaccines

The Flaviviridae is a family of about 70 mostly arthropod-borne viruses many of which are major public health problems with members present in most continents. Among the most important are yellow fever (YF), dengue (DEN) with its 4 serotypes and Japanese escephalitis (JE) virus. A live attenuated virus is used as a cost-effective, safe and efficacious vaccine against YF but no other live flavivirus vaccines have been licensed. The development of recombinant DNA technology and its application to study flavivirus genome structure and expression has opened new possibilities for flavivirus vaccine development. The new approaches include the use of cDNAs encompassing the whole viral genome to generate infectious RNA after in vitro transcription. This methodology allows the genetic mapping of specific viral functions and the design of viral mutants with considerable potential as new live attenuated virues. The use of infectious cDNA as a carrier for heterologous antigens is a gaining importance since chimeric viruses are shown to be viable, immunogenic and less virulent in some cases as compared to the parental viruses. The use of DNA to overcome intrinsic mutation rates of RNA virus populations in conjunction with vaccine production in cell culture should improve the reliability and lower the cost of live attenuated vaccines.