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Is Hepatitis Delta infections important in Brazil?

ABSTRACT: The Hepatitis Delta Virus (HDV) can increase the incidence of fulminant hepatitis. For this infection occurs, the host must also be infected with Hepatitis B Virus. Previous studies demonstrated the endemicity and near exclusivity of this infection in the Amazon region, and as a consequence of the difficulty in accessing this area we used dried blood spots (DBS) in sample collection. The aims of this study were to investigate the presence of recombination, to analyze the epidemiology, ancestry and evolutionary pressures on HDV in Brazil.Blood samples from 50 individuals were collected using dried-blood spots (DBS 903, Whatman), and sent via regular mail to Retrovirology Laboratory from Federal University of São Paulo, where the samples were processed. In the analysis the following software were used: PhyML, RDP, BEAST, jModelTest and CODEML.Our results confirm the prevalence of HDV-3 in the Amazon region of Brazil, with the absence of inter-genotypic recombination. It was identified a positive selection in probable epitopes of HDV on B lymphocytes that might indicate that the virus is changing to escape the humoral response of the host. The analysis of the time of the most common ancestor demonstrated the exponential growth of this virus in late 1970s that lasted until 1995, after which it remained constant. It was also observed a probable founder effect in two cities, which demonstrate the need to focus on prevention methods against HBV/HDV infection.We confirmed the prevalence of HDV-3 in the Amazon region of Brazil, without inter-genotypic recombination. The analysis of the time of the most common ancestor showed that this infection remain constant in the studied area. Taking into account the probable founder effect established in the cities of Rio Branco and Porto Velho, a focus on preventive methods is recommended against these infections.

SUBMITTER: Cicero MF

PROVIDER: S-EPMC5041555 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Is Hepatitis Delta infections important in Brazil?

Cicero Maira Ferreira MF Pena Nathalia Mantovani NM Santana Luiz Claudio LC Arnold Rafael R Azevedo Rafael Gonçalves RG Leal Élcio de Souza ÉS Diaz Ricardo Sobhie RS Komninakis Shirley Vasconcelos SV

BMC infectious diseases 20160929 1

<h4>Background</h4>The Hepatitis Delta Virus (HDV) can increase the incidence of fulminant hepatitis. For this infection occurs, the host must also be infected with Hepatitis B Virus. Previous studies demonstrated the endemicity and near exclusivity of this infection in the Amazon region, and as a consequence of the difficulty in accessing this area we used dried blood spots (DBS) in sample collection. The aims of this study were to investigate the presence of recombination, to analyze the epide ...[more]

PMID: 27686363

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Project description:BackgroundHepatitis B virus (HBV) and hepatitis D virus (HDV) represent important public health problems in the Western Amazon region with reported cases of fulminant hepatitis. This cross sectional study describes HBV and HDV genotypes circulating in the Brazilian Amazon region.MethodsHBsAg positive individuals (n = 224) were recruited in Manaus/Amazonas State (130 blood donors from the Hematology and Hemotherapy Foundation from Amazonas/HEMOAM; 60 subjects from outpatient clinic) and in Eirunepe city (n = 34) from 2003-2009. Most participants (n = 153) lived in Manaus, 63 were from 20 remote isolated municipalities, 8 lived outside Amazonas State. Genotyping was based on PCR products: HBV genotype A-F specific primers, restricted length polymorphism for HDV. HDV isolates were directly sequenced (delta antigen 405 nucleotide fragment) and phylogenetic analysis performed (MEGA; neighbor-joining, Kimura's two parameter).ResultsMost participants were young adult males and HBV mono-infection predominated (70.5%, 158/224). Among blood donors, outpatient subjects and individuals from Eirunepe, HBV/A prevailed followed by HBV/D and F (p > 0.05). HBV/A was more frequent in blood donors (p < 0.05). HBV-HDV coinfection rate was 8.5% in blood donors (11/130), 65.0% (39/60) in outpatient subjects and 47.0% (16/34) in individuals from Eirunepe. Compared to blood donors, coinfection was higher in outpatient subjects (65.0% versus 8.5%; RR = 5.0; CI 3.4-7.9; p < 0.0001) and in subjects from Eirunepe (47.0% versus 8.5%; RR = 5.5; CI 3.0-9.9; p < 0.0001). HBV-HDV coinfection rates were higher in patients from highly endemic remote cities. Only HDV genotype 3 was detected, HBV/F-HDV/3 predominated (20/38; 52.7%), followed by HBV/A-HDV/3 (31.6%; 12/38) and HBV/D-HDV/3 (15.8%; 6/38).ConclusionsThe description of HBV and HDV genotypes circulating in the western Amazon can contribute to a better understanding of their relevance on the regional epidemics. These infections are highly endemic in the Amazon where their control is challenged by its vast territorial dimension with small, hard-to-reach municipalities dispersed into the jungle and populated by diverse ethnic groups.

Project description:Hepatitis delta virus (HDV) is a satellite of hepatitis B virus that increases the severity of acute and chronic liver disease. HDV produces three processed RNAs that accumulate in infected cells: the circular genome; the circular antigenome, which serves as a replication intermediate; and lesser amounts of the mRNA, which encodes the sole viral protein, hepatitis delta antigen (HDAg). The HDV genome and antigenome RNAs form ribonucleoprotein complexes with HDAg. Although HDAg is required for HDV replication, it is not known how the relative amounts of HDAg and HDV RNA affect replication, or whether HDAg synthesis is regulated by the virus. Using a novel transfection system in which HDV replication is initiated using in vitro-synthesized circular HDV RNAs, HDV replication was found to depend strongly on the relative amounts of HDV RNA and HDAg. HDV controls these relative amounts via differential effects of HDAg on the production of HDV mRNA and antigenome RNA, both of which are synthesized from the genome RNA template. mRNA synthesis is favored at low HDAg levels but becomes saturated at high HDAg concentrations. Antigenome RNA accumulation increases linearly with HDAg and dominates at high HDAg levels. These results provide a conceptual model for how HDV antigenome RNA production and mRNA transcription are controlled from the earliest stage of infection onward and also demonstrate that, in this control, HDV behaves similarly to other negative-strand RNA viruses, even though there is no genetic similarity between them.IMPORTANCE Hepatitis delta virus (HDV) is a satellite of hepatitis B virus that increases the severity of liver disease; approximately 15 million people are chronically infected worldwide. There are no licensed therapies available. HDV is not related to any known virus, and few details regarding its replication cycle are known. One key question is whether and how HDV regulates the relative amounts of viral RNA and protein in infected cells. Such regulation might be important because the HDV RNA and protein form complexes that are essential for HDV replication, and the proper stoichiometry of these complexes could be critical for their function. Our results show that the relative amounts of HDV RNA and protein in cells are indeed important for HDV replication and that the virus does control them. These observations indicate that further study of these regulatory mechanisms is required to better understand replication of this serious human pathogen.

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Is Hepatitis Delta infections important in Brazil?

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Is Hepatitis Delta infections important in Brazil?

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