RESUMEN
The diagnosis of the rare neoplasm histiocytic sarcoma (HS) relies on morphology and the presence of immunophenotypic features of histiocytic lineage. More than 57 cases, including 16 cases involving the gastrointestinal (GI) tract, have been described since the World Health Organization issued its classification system for tumors of hematopoietic and lymphoid tissue in 2001. HS is often diagnosed in its late stages, at which point the prognosis is poor. Only a small proportion of these patients can undergo surgical resection with curative intent. The present report describes how HS can be diagnosed at a stage of favorable prognosis using balloon enteroscopy (BE), thereby enabling surgical resection before the development of metastases. This strategy is reviewed in the setting of a patient with jejunal HS, followed by a discussion of data from 16 other reported cases of GI HS.
Asunto(s)
Endoscopía Gastrointestinal/métodos , Sarcoma Histiocítico/diagnóstico , Neoplasias Intestinales/diagnóstico , Femenino , Humanos , Intestino Delgado/patología , Persona de Mediana EdadRESUMEN
The JFH1 strain of hepatitis C virus (HCV) is unique among HCV isolates, in that the wild-type virus can traverse the entire replication cycle in cultured cells. However, without adaptive mutations, only low levels of infectious virus are produced. In the present study, the effects of five mutations that were selected during serial passage in Huh-7.5 cells were studied. Recombinant genomes containing all five mutations produced 3-4 logs more infectious virions than did wild type. Neither a coding mutation in NS5A nor a silent mutation in E2 was adaptive, whereas coding mutations in E2, p7, and NS2 all increased virus production. A single-cycle replication assay in CD81-deficient cells was developed to study more precisely the effect of the adaptive mutations. The E2 mutation had minimal effect on the amount of infectious virus released but probably enhanced entry into cells. In contrast, both the p7 and NS2 mutations independently increased the amount of virus released.
Asunto(s)
Adaptación Biológica/genética , Hepacivirus/genética , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Humanos , Mutación/genética , Replicación ViralRESUMEN
GB virus B (GBV-B) causes acute hepatitis in experimentally infected tamarins. We compared evolutionary features in acute resolving and persistent GBV-B infection. We detected no evidence of evolution in four animals with clearance during weeks 9-12, whereas three animals with clearance during weeks 13-26 had several substitutions in their polyprotein sequence. A single tamarin had long-term GBV-B viraemia; analysis of virus recovered at weeks 2, 5, 12, 20, 26, 52 and 104 demonstrated that mutations accumulated over time. Overall, the amino acid substitution rate was 3.5x10(-3) and 1.1x10(-3) substitutions per site year(-1) during weeks 1-52 and 53-104, respectively. Thus, there was a significant decrease in evolution over time, as found for hepatitis C virus. The rate of non-synonymous substitution per non-synonymous site compared with that of synonymous substitution per synonymous site decreased over time, suggesting reduction of positive selective pressure. These data demonstrate that prolonged GBV-B infection is associated with viral evolution.
Asunto(s)
Evolución Molecular , Virus GB-B/clasificación , Virus GB-B/genética , Hepatitis Viral Animal/virología , Enfermedades de los Monos/virología , Sustitución de Aminoácidos/genética , Animales , Modelos Animales de Enfermedad , Productos del Gen pol/genética , LeontopithecusRESUMEN
Both viral and host factors are thought to influence the pathogenesis of hepatitis C virus (HCV) infection. We studied strain HC-TN (genotype 1a), which caused fulminant hepatic failure in a patient and, subsequently, severe hepatitis in a chimpanzee (CH1422), to analyze the relationship between disease severity, host immune response, viral evolution, and outcome. A second chimpanzee (CH1581) was infected from CH1422 plasma, and a third chimpanzee (CH1579) was infected from RNA transcripts of a consensus cDNA of HC-TN (pHC-TN). RNA transcripts of pHC-TN did not replicate in Huh7.5 cells, which were recently found to be susceptible to infection with another fulminant HCV strain (JFH1). The courses of viremia were similar in the three animals. However, CH1581 and CH1579 developed a less severe acute hepatitis than CH1422. CH1579 and CH1422 resolved the infection, whereas CH1581 became persistently infected. CH1579 and CH1581, despite their differing outcomes, both developed significant intrahepatic cellular immune responses, but not antibodies to the envelope glycoproteins or neutralizing antibodies, during the acute infection. We analyzed the polyprotein sequences of virus recovered at five and nine time points from CH1579 and CH1581, respectively, during the first year of follow-up. High mutation rates and high proportions of nonsynonymous mutations suggested immune pressure and positive selection in both animals. Changes were not selected until after the initial decrease in virus titers and after the development of immune responses and hepatitis. Subsequently, however, mutations emerged repeatedly in both animals. Overall, our results indicate that disease severity and outcome of acute HCV infection depend primarily on the host response.
Asunto(s)
Evolución Molecular , Hepacivirus/genética , Hepatitis C/genética , Fallo Hepático Agudo/genética , Mutación , ARN Viral/genética , Enfermedad Aguda , Animales , Anticuerpos Antivirales/inmunología , Secuencia de Bases , Línea Celular , Hepacivirus/inmunología , Hepacivirus/aislamiento & purificación , Hepatitis C/inmunología , Hepatitis C/patología , Humanos , Hígado/inmunología , Hígado/patología , Hígado/virología , Fallo Hepático Agudo/inmunología , Fallo Hepático Agudo/patología , Fallo Hepático Agudo/virología , Datos de Secuencia Molecular , Pan troglodytes , ARN Viral/inmunología , Especificidad de la Especie , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/inmunologíaRESUMEN
GB virus B (GBV-B), which infects tamarins, is the virus most closely related to hepatitis C virus (HCV). HCV has a protein (p7) that is believed to form an ion channel. It is critical for viability. In vitro studies suggest that GBV-B has an analogous but larger protein (p13). We found that substitutions of the -1 and/or -3 residues of the putative cleavage sites (amino acid 613/614 and 732/733) abolished processing in vitro and rendered an infectious GBV-B clone nonviable in tamarins. Internal cleavage was predicted at two sites (amino acid 669/670 and 681/682), and in vitro analysis indicated processing at both sites, suggesting that p13 is processed into two components (p6 and p7). Mutants with substitution at amino acid 669 or 681 were viable in vivo, but the recovered viruses had changes at amino acid 669 and 681, respectively, which restored cleavage. A mutant lacking amino acid 614-681 (p6 plus part of p7) was nonviable. However, a mutant lacking amino acid 614-669 (p6) produced high titer viremia and acute resolving hepatitis; viruses recovered from both animals lacked the deleted sequence and had no other mutations. Thus, p6 was dispensable but p7 was essential for infectivity. The availability of a recombinant GBV-B virus containing a p7 protein with similarities to the HCV p7 will enhance the relevance of this model and will be of importance for identifying compounds that inhibit p7 function as additional therapeutic agents.