RESUMO
Hepatitis B virus (HBV) variants may either emerge in patients with chronic hepatitis B (CHB) as a result of positive selection pressure exerted by their own immune response, or during therapy with nucleos(t)ide analogues (NAs). Naturally occurring HBV variants with primary antiviral resistance are rarely observed. The aim of this study was to retrospectively analyze the (eventual) circulation of HBV variants with natural resistance to NAs currently used as therapy for CHB in Argentina. This study reports 13 cases of CHB-infected patients with natural antiviral resistance to at least one NA. Five of them were also carriers of S-variants that might escape the humoral immune system recognition with potential resistance to adefovir. In addition to the already reported A2 HBV subgenotype association to NAs natural resistance, E and F genotypes association to such resistance is described for the first time. These findings suggest that sequence analysis of the HBV reverse transcriptase might be an essential tool before starting antiviral therapy, in order to choose the proper NAs for optimizing the therapeutic management of chronically infected patients. Moreover, the circulation and transmission of S-mutants with resistance to such antiviral drugs should be of public health concern as they may represent an additional risk for the community.
Assuntos
Adenina/análogos & derivados , Antivirais/farmacologia , Farmacorresistência Viral , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/virologia , Mutação de Sentido Incorreto , Organofosfonatos/farmacologia , Adenina/farmacologia , Adolescente , Adulto , Argentina , Criança , Pré-Escolar , Feminino , Genótipo , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Genomic heterogeneity and quasispecies composition of GB virus C (GBV-C) within plasma and lymphocyte subsets in a naturally infected blood donor were investigated. For this purpose, fragments from the 5' untranslated region (5' UTR) and the E2 gene recovered from plasma, B and T lymphocytes, were cloned and sequenced. A total of 63 clones was analysed: 95.2 % of them (n=60) - obtained from plasma and cells - were assigned to genotype 2b, while only three derived from plasma corresponded to genotyope 3. The G215A transition within this region was present in 90.9 % of the clones from B lymphocytes, but absent in the remaining cell compartments (P<0.01). Apparently, most of the circulating GBV-C quasispecies in this blood donor were related to the viral population infecting CD8(+) T cells, and B cells to a lesser extent. This is the first report showing the quasispecies nature of GBV-C in lymphocyte subsets within peripheral blood mononuclear cells.
Assuntos
Infecções por Flaviviridae/virologia , Vírus GB C/classificação , Vírus GB C/genética , Hepatite Viral Humana/virologia , Subpopulações de Linfócitos/virologia , Sequência de Bases , Doadores de Sangue , Especiação Genética , Variação Genética , Humanos , Dados de Sequência Molecular , Filogenia , Proteínas ViraisRESUMO
Genotype E hepatitis B virus (HBV) was detected in two Argentine sisters exhibiting an African mitochondrial lineage. One of them (who had been vaccinated against HBV) exhibited anti-HBs cocirculating antibodies without HBsAg escape mutants, while her unvaccinated sister showed a D144A HBsAg escape mutant without anti-HBs antibodies. Both sisters carried an unusual L209V substitution within HBsAg.
Assuntos
Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/classificação , Vírus da Hepatite B/isolamento & purificação , Adolescente , Adulto , Argentina , População Negra , Portador Sadio/virologia , Pré-Escolar , Feminino , Genótipo , Hepatite B/imunologia , Hepatite B/prevenção & controle , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/genética , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/genética , Humanos , Mutação , Filogenia , VacinaçãoRESUMO
Serum hepatitis B virus (HBV) DNA was extracted from a chronically infected patient with cocirculation of hepatitis B surface antigen (HBsAg) and anti-HBs antibodies. Direct PCR and clone-derived sequences of the S and overlapped P genes were obtained. DNA sequences and phylogenetic analysis ascribed this isolate to genotype A (serotype adw2). Five of six HBV DNA clones exhibited point mutations inside and outside the major hydrophilic region, while the sixth clone exhibited a genotype A "wild-type" amino acid sequence. Observed replacements included both humoral and/or cellular (major histocompatibility complex class I [MHC-I] and MHC-II) HBV mutated epitopes, such as S45A, P46H, L49H, C107R, T125A, M133K, I152F, P153T, T161S, G185E, A194T, G202R, and I213L. None of these mutants were individually present within a given clone. The I213L replacement was the only one observed in the five clones carrying nonsynonymous mutations in the S gene. Some of the amino acid substitutions are reportedly known to be responsible for the emergence of immune escape mutants. C107R replacement prevents disulfide bonding, thus disrupting the first loop of the HBsAg. Circulation of some of these mutants may represent a potential risk for the community, since neither current hepatitis B vaccines nor hyperimmune hepatitis B immune globulin are effectively prevent the liver disease thereto associated. Moreover, some of the recorded HBsAg variants may influence the accuracy of the results obtained with currently used diagnostic tests.