RESUMO
Cowpox virus (CPXV) belongs to the genus Orthopoxvirus in the Poxviridae family and is endemic in western Eurasia. Based on seroprevalence studies in different voles from continental Europe and UK, voles are suspected to be the major reservoir host. Recently, a CPXV was isolated from a bank vole (Myodes glareolus) in Germany that showed a high genetic similarity to another isolate originating from a Cotton-top tamarin (Saguinus oedipus). Here we characterize this first bank vole-derived CPXV isolate in comparison to the related tamarin-derived isolate. Both isolates grouped genetically within the provisionally called CPXV-like 3 clade. Previous phylogenetic analysis indicated that CPXV is polyphyletic and CPXV-like 3 clade represents probably a different species if categorized by the rules used for other orthopoxviruses. Experimental infection studies with bank voles, common voles (Microtusarvalis) and Wistar rats showed very clear differences. The bank vole isolate was avirulent in both common voles and Wistar rats with seroconversion seen only in the rats. In contrast, inoculated bank voles exhibited viral shedding and seroconversion for both tested CPXV isolates. In addition, bank voles infected with the tamarin-derived isolate experienced a marked weight loss. Our findings allow for the conclusion that CPXV isolates might differ in their replication capacity in different vole species and rats depending on their original host. Moreover, the results indicate host-specific differences concerning CPXV-specific virulence. Further experiments are needed to identify individual virulence and host factors involved in the susceptibility and outcome of CPXV-infections in the different reservoir hosts.
Assuntos
Arvicolinae/virologia , Vírus da Varíola Bovina/classificação , Reservatórios de Doenças/virologia , Animais , Vírus da Varíola Bovina/fisiologia , Modelos Animais de Doenças , Reservatórios de Doenças/classificação , Feminino , Genoma Viral , Masculino , Ratos , Ratos Wistar , Saguinus/virologia , Soroconversão , Replicação Viral , Eliminação de Partículas ViraisRESUMO
Cowpox virus (CPXV) was isolated from a fatal outbreak among cotton-top tamarins. Samples from healthy common marmosets in contact were also CPXV genome positive. The CPXV isolated from the cotton-top tamarins exhibited a unique hemagglutinin sequence. Pathogenicity investigations using a Wistar rat model characterized the isolate as low pathogenic.
Assuntos
Vírus da Varíola Bovina/isolamento & purificação , Varíola Bovina/veterinária , Surtos de Doenças/veterinária , Doenças dos Macacos/epidemiologia , Saguinus/virologia , Animais , Varíola Bovina/epidemiologia , Varíola Bovina/virologia , Vírus da Varíola Bovina/genética , Vírus da Varíola Bovina/patogenicidade , Modelos Animais de Doenças , Feminino , Alemanha/epidemiologia , Hemaglutininas Virais/genética , Masculino , Doenças dos Macacos/virologia , Filogenia , Ratos , Ratos Wistar , Análise de Sequência de DNA/veterináriaRESUMO
Flaviviruses related to hepatitis C virus (HCV) in suitable animal models may provide further insight into the role that cellular immunity contributes to spontaneous clearance of HCV. We characterised changes in lymphocyte populations in tamarins with an acute GBV-B infection, a hepatitis virus of the flaviviridae. Major immune cell populations were monitored in peripheral and intra-hepatic lymphocytes at high viraemia or following a period when peripheral virus was no longer detected. Limited changes in major lymphocyte populations were apparent during high viraemia; however, the proportions of CD3(+) lymphocytes decreased and CD20(+) lymphocytes increased once peripheral viraemia became undetectable. Intrahepatic lymphocyte populations increased at both time points post-infection. Distinct expression patterns of PD-1, a marker of T-cell activation, were observed on peripheral and hepatic lymphocytes; notably there was elevated PD-1 expression on hepatic CD4(+) T-cells during high viraemia, suggesting an activated phenotype, which decreased following clearance of peripheral viraemia. At times when peripheral vRNA was not detected, suggesting viral clearance, we were able to readily detect GBV-B RNA in the liver, indicative of long-term virus replication. This study is the first description of changes in lymphocyte populations during GBV-B infection of tamarins and provides a foundation for more detailed investigations of the responses that contribute to the control of GBV-B infection.
Assuntos
Modelos Animais de Doenças , Infecções por Flaviviridae/virologia , Vírus GB B/fisiologia , Hepatite Viral Humana/virologia , Fígado/imunologia , Saguinus , Animais , Infecções por Flaviviridae/imunologia , Vírus GB B/imunologia , Hepatite Viral Humana/imunologia , Humanos , Fígado/virologia , Ativação Linfocitária , Saguinus/imunologia , Saguinus/virologia , Linfócitos T/imunologia , Viremia/imunologia , Viremia/virologia , Replicação ViralRESUMO
The infection of red-bellied tamarins (Saguinus labiatus) with GB virus B (GBV-B) is an important surrogate model of hepatitis C virus infection in man. To fully exploit the value of this model, we have characterised MHC class I G and class II DRB alleles in eight tamarins representing a cross-section of a UK breeding colony. The results indicated a high degree of classes I and II DRB allele sharing. Each animal transcribed three to four putative surface-expressed class I alleles and two to four class II DRB alleles. Most animals also transcribed at least one class I allele predicted to result in a C-terminal truncated protein. These results represent the first description of MHC polymorphism in this species and provide a foundation for characterisation of MHC diversity in breeding populations of red-bellied tamarins. The data will facilitate the identification of associations between MHC polymorphism and control of viral infections, and detailed dissection of cellular immune responses against GBV-B.
Assuntos
Infecções por Flaviviridae/imunologia , Vírus GB B , Genes MHC da Classe II , Genes MHC Classe I , Hepatite Viral Animal/imunologia , Hepatite Viral Humana/imunologia , Saguinus/imunologia , Animais , Modelos Animais de Doenças , Infecções por Flaviviridae/genética , Frequência do Gene , Hepatite Viral Animal/genética , Hepatite Viral Humana/genética , Humanos , Imunidade Celular/genética , Polimorfismo Genético , Saguinus/genética , Saguinus/virologiaRESUMO
GB virus B (GBV-B) is closely related to hepatitis C virus (HCV), infects small non-human primates, and is thus a valuable surrogate for studying HCV. Despite significant differences, the 5' nontranslated RNAs (NTRs) of these viruses fold into four similar structured domains (I-IV), with domains II-III-IV comprising the viral internal ribosomal entry site (IRES). We previously reported the in vivo rescue of a chimeric GBV-B (vGB/III(HC)) containing HCV sequence in domain III, an essential segment of the IRES. We show here that three mutations identified within the vGB/III(HC) genome (within the 3'NTR, upstream of the poly(U) tract, and NS5A coding sequence) are necessary and sufficient for production of this chimeric virus following intrahepatic inoculation of synthetic RNA in tamarins, and thus apparently compensate for the presence of HCV sequence in domain III. To assess the mechanism(s) underlying these compensatory mutations, and to determine whether 5'NTR subdomains participating in genome replication do so in a virus-specific fashion, we constructed and evaluated a series of chimeric subgenomic GBV-B replicons in which various 5'NTR subdomains were substituted with their HCV homologs. Domains I and II of the GBV-B 5'NTR could not be replaced with HCV sequence, indicating that they contain essential, virus-specific RNA replication elements. In contrast, domain III could be swapped with minimal loss of genome replication capacity in cell culture. The 3'NTR and NS5A mutations required for rescue of the related chimeric virus in vivo had no effect on replication of the subgenomic GBneoD/III(HC) RNA in vitro. The data suggest that in vivo fitness of the domain III chimeric virus is dependent on a cooperative interaction between the 5'NTR, 3'NTR and NS5A at a step in the viral life cycle subsequent to genome replication, most likely during particle assembly. Such a mechanism may be common to all hepaciviruses.
Assuntos
Vírus GB B/fisiologia , Hepacivirus/fisiologia , RNA não Traduzido/metabolismo , RNA Viral/metabolismo , Proteínas Virais/metabolismo , Animais , Sequência de Bases , Linhagem Celular Tumoral , Vírus GB B/genética , Vírus GB B/patogenicidade , Genoma Viral/genética , Hepacivirus/genética , Hepacivirus/patogenicidade , Humanos , Dados de Sequência Molecular , Mutação/genética , Conformação de Ácido Nucleico , Biossíntese de Proteínas , RNA não Traduzido/química , RNA não Traduzido/genética , RNA Viral/química , RNA Viral/genética , Replicon , Saguinus/virologia , Análise de Sequência de RNA , Replicação ViralRESUMO
GB virus-B (GBV-B) is the virus most closely related to hepatitis C virus (HCV). Thus, we have used GBV-B infection of tamarins, which develop acute hepatitis following experimental infection, as a surrogate model to study protective immunity. As challenge virus, we first produced a GBV-B pool from an infected tamarin, which was not infected with the related GBV-A viruses. Its infectivity titer was 10(6.6) tamarin 50% infectious doses per ml. Next, two tamarins that were convalescent from recombinant GBV-B infection were re-challenged. In the original infection viremia persisted for 8 and 12 weeks, respectively, and both animals developed moderately severe hepatitis. Each tamarin was re-challenged four times with 10(4.3) tamarin 50% infectious doses of the GBV-B challenge virus. In one animal, each re-challenge produced 1-2 weeks of viremia; hepatitis was observed following the first re-challenge. In the other animal, however, only the first re-challenge produced viremia, lasting 1 week. During the primary infection, peak GBV-B titers were about 10(8) genome equivalents/ml in both animals; following re-challenges, peak titers ranged from 10(3) to 10(6) genome equivalents/ml. Analysis of the polyprotein sequence of viruses recovered from both animals following the first re-challenge demonstrated that these did not represent immune escape variants since mutations were not detected. Neutralization studies suggested that the immunity was not humoral in nature. We also demonstrated that the immunity was long-lived: 1 year after the fourth challenge, the animal with sterilizing immunity had low titer viremia for only 1 week following an additional challenge.
Assuntos
Infecções por Flaviviridae/imunologia , Vírus GB B/imunologia , Hepatite Viral Animal/virologia , Poliproteínas/imunologia , Saguinus/virologia , Animais , Infecções por Flaviviridae/virologia , Vírus GB B/genética , Vírus GB B/patogenicidade , Hepacivirus/genética , Doenças dos Macacos/virologia , RNA Viral/química , RNA Viral/genética , ViremiaRESUMO
Only humans and chimpanzees are fully permissive for replication of hepatitis C virus (HCV), an important cause of liver cirrhosis and cancer worldwide. The absence of suitable animal models limits opportunities for in vivo evaluation of candidate hepatitis C therapeutics and slows progress in the field. Here, we describe a chimeric virus derived from GB virus B (GBV-B), an unclassified hepatotropic member of the family Flaviviridae that is closely related to HCV and infects tamarins (Saguinus sp.), in which a functionally important HCV regulatory sequence replaced an analogous sequence in the 5' nontranslated region (5'NTR) of the GBV-B genome. The transplanted sequence comprised domain III of the internal ribosome entry site (IRES), which directly binds the 40S ribosome subunit and is a target for candidate therapeutics. The chimeric 5'NTR retained ribosome binding activity and was competent in directing protein translation both in cell-free translation reactions and in transfected primary tamarin hepatocyte cultures. Virus rescued from the chimeric RNA replicated in the liver of tamarins, causing biochemical and histopathological changes typical of viral hepatitis. However, adaptive mutations were required elsewhere in the genome for efficient replication. Virus was not rescued from other, translationally competent, chimeric RNAs in which domain II of the IRES was exchanged. Thus, the 5'NTR appears to contain virus-specific replication signals that interact with other sites within the viral genome or with viral proteins. In conclusion, such novel chimeric flaviviruses offer opportunities for new insights into HCV replication mechanisms, while potentially facilitating the evaluation of candidate therapeutics in vivo.
Assuntos
Modelos Animais de Doenças , Infecções por Flaviviridae/fisiopatologia , Vírus GB B/genética , Hepacivirus/genética , Hepatite Viral Animal/fisiopatologia , Saguinus/virologia , Regiões 5' não Traduzidas/genética , Animais , Quimera , DNA Complementar , Infecções por Flaviviridae/virologia , Vírus GB B/crescimento & desenvolvimento , Genoma Viral , Hepatite Viral Animal/virologia , Plasmídeos/genética , RNA Viral/genética , Ribossomos/genética , Ribossomos/virologiaRESUMO
The lack of a preventive vaccine, coupled with common unresponsiveness to treatment and coinfection with HIV, has made HCV a major threat to public health. The authors review in vitro and in vivo models that are being used to study HCV and to develop new treatments and preventive measures.
Assuntos
Modelos Animais de Doenças , Hepacivirus , Hepatite C , Camundongos Transgênicos/virologia , Pan troglodytes/virologia , Saguinus/virologia , Tupaiidae/virologia , Animais , Técnicas de Cultura de Células , Hepatócitos/imunologia , Hepatócitos/virologia , Camundongos , Replicação ViralRESUMO
Noroviruses, with Norwalk virus as the prototype strain, are the most common cause of viral gastroenteritis in people of all ages. Limited information on the immunology of Norovirus infections has been obtained by studies both in the natural setting and in experimentally infected volunteers. Interpretation of these studies is difficult due to the lack of information on the history of Norovirus exposure and the cross-reactivity of antibodies. An animal model for Norovirus infections would be important to study the immune response, e.g., for vaccine assessment. In the present study the susceptibility of common marmosets, cotton top tamarins, cynomolgus, and rhesus macaques to Norovirus infection was tested. Following oral inoculation, low level replication may have occurred in common marmosets and cotton top tamarins but not in cynomolgus macaques, based on short-term viral shedding; neither clinical symptoms nor antibody responses were observed in these species. In contrast, rhesus macaques were found susceptible to Norwalk virus infection as one animal shed virus for a longer period of time and developed Norwalk virus specific IgM and IgG responses. Further research on Norovirus susceptibility in rhesus macaques may yield an animal model to study the immune response and pathogenesis after Norovirus infection.
Assuntos
Infecções por Caliciviridae/imunologia , Norovirus/isolamento & purificação , Norovirus/patogenicidade , Sistema ABO de Grupos Sanguíneos , Animais , Anticorpos Antivirais/sangue , Doenças dos Símios Antropoides/epidemiologia , Antígenos de Grupos Sanguíneos , Infecções por Caliciviridae/sangue , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/veterinária , Callithrix/imunologia , Callithrix/virologia , Modelos Animais de Doenças , Fezes/virologia , Macaca fascicularis/imunologia , Macaca fascicularis/virologia , Macaca mulatta/imunologia , Macaca mulatta/virologia , Doenças dos Macacos/epidemiologia , Norovirus/imunologia , Pan troglodytes/virologia , RNA Viral/isolamento & purificação , Saguinus/imunologia , Saguinus/virologia , Eliminação de Partículas Virais/genéticaRESUMO
GB virus B (GBV-B), the virus most closely related to hepatitis C virus (HCV), infects tamarins and causes acute hepatitis. The 3' untranslated region (UTR) of an infectious GBV-B clone (pGBB) has a proximal short sequence followed by a poly(U) tract and a 3' terminal sequence. Our investigators previously demonstrated that the 3' terminal sequence was critical for in vivo infectivity. Here, we tested the effect of deleting the short sequence and/or the poly(U) tract from pGBB; infectivity of each mutant was tested by intrahepatic transfection of two tamarins with transcribed RNA. A mutant lacking both regions was not viable. However, mutants lacking either the short sequence or the poly(U) tract were viable. All four tamarins had a wild-type-like acute infection and developed acute hepatitis. Whereas we found that five tamarins transfected with the wild-type clone pGBB had acute resolving infection, one tamarin transfected with the poly(U) deletion mutant became persistently infected. This animal had viremia and hepatitis until its death at week 90. The genomes recovered at weeks 2, 7, 15, 20, 60, and 90 lacked the poly(U) stretch. Eight amino acid changes were identified at week 90. One change, in the putative p7 protein, was dominant at week 15. Thus, persistence of GBV-B, like persistence of HCV, was associated with the emergence of virus variants. Four tamarins inoculated with serum collected at weeks 2 and 90 from the tamarin with persistent infection had an acute resolving infection. Nonetheless, the demonstration that GBV-B can persist in tamarins strengthens its relevance as a surrogate model for the study of HCV.
Assuntos
Regiões 3' não Traduzidas/genética , Vírus GB B/genética , Vírus GB B/fisiologia , Engenharia Genética , Mutagênese/genética , Saguinus/virologia , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , Infecções por Flaviviridae/virologia , Vírus GB B/patogenicidade , Genoma Viral , Proteínas de Fluorescência Verde , Hepatite Viral Animal/virologia , Proteínas Luminescentes/genética , Dados de Sequência Molecular , Poli U/genética , Poliproteínas/genética , Deleção de Sequência/genética , Fatores de Tempo , Transfecção , Replicação ViralRESUMO
GB virus B (GBV-B), a flavivirus closely related to HCV, has previously been shown to infect and replicate to high titers in tamarins (Saguinus sp.). This study describes the use of GBV-B infection and replication in the common marmoset (Callithrix jacchus) for the successful development and validation of a surrogate animal model for hepatitis C virus (HCV). Infection of marmosets with GBV-B produced a viremia that peaked at 10(8) to 10(9) genome copies/ml for a period of 40 to 60 days followed by viral clearance at 60 to 80 days postinfection. Passage of the initial tamarin-derived GBV-B in marmosets produced an infectious stock that gave a more reproducible and consistent infection in the marmoset. Titration of the virus stocks in vivo indicated that they contained 1 infectious unit for every 1,000 genome copies. Cultures of primary marmoset hepatocytes were also successfully infected with GBV-B, with high levels of virus detected in supernatants and cells for up to 14 days postinfection. Treatment of GBV-B-infected hepatocyte cultures with a novel class of HCV protease inhibitor (pyrrolidine 5,5 trans-lactams) reduced viral levels by more than 2 logs. Treatment of GBV-B-infected marmosets with one such inhibitor resulted in a 3-log drop in serum viral titer over 4 days of therapy. These studies provide the first demonstration of the in vivo efficacy of a small-molecule inhibitor for HCV in an animal model and illustrate the utility of GBV-B as a surrogate animal model system for HCV.
Assuntos
Callithrix/virologia , Modelos Animais de Doenças , Infecções por Flaviviridae/veterinária , Vírus GB B/patogenicidade , Hepatite Viral Animal/fisiopatologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Animais , Células Cultivadas , Infecções por Flaviviridae/tratamento farmacológico , Infecções por Flaviviridae/fisiopatologia , Infecções por Flaviviridae/virologia , Vírus GB B/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Hepatite C/fisiopatologia , Hepatite C/virologia , Hepatite Viral Animal/tratamento farmacológico , Hepatite Viral Animal/virologia , Hepatócitos/virologia , Humanos , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico , Saguinus/virologia , Replicação ViralRESUMO
Progress in understanding the pathogenesis of hepatitis C virus (HCV) has been slowed by the absence of tractable small animal models. Whereas GB virus B (GBV-B, an unclassified flavivirus) shares a phylogenetic relationship and several biologic attributes with HCV, including hepatotropism, it is not known to cause persistent infection, a hallmark of HCV. Here, we document persistent GBV-B infection in one of two healthy tamarins (Saguinus oedipus) inoculated intrahepatically with infectious synthetic RNA. High-titer viremia (108 to 109 genome equivalents per ml) and transiently elevated serum alanine transaminase activities were present from weeks 4 to 12 postinoculation in both animals. However, whereas GBV-B was eliminated from one animal by 20 weeks, the second animal remained viremic (103 to 107 genome equivalents per ml) for >2 years, with alanine transaminase levels becoming elevated again before spontaneous resolution of the infection. A liver biopsy taken late in the course of infection demonstrated hepatitis with periportal mononuclear infiltrates, hepatocellular microvesicular changes, cytoplasmic lipid droplets, and disordered mitochondrial ultrastructure, findings remarkably similar to chronic hepatitis C. GBV-B-infected hepatocytes contained numerous small vesicular membranous structures resembling those associated with expression of HCV nonstructural proteins, and sequencing of GBV-B RNA demonstrated a rate of molecular evolution comparable to that of HCV. We conclude that GBV-B is capable of establishing persistent infections in healthy tamarins, a feature that substantially enhances its value as a model for HCV. Mitochondrial structural changes and altered lipid metabolism leading to steatosis are conserved features of the pathogenesis of chronic hepatitis caused by these genetically distinct flaviviruses.
Assuntos
Infecções por Flaviviridae/etiologia , Vírus GB B/genética , Vírus GB B/patogenicidade , Hepatite Viral Animal/etiologia , RNA Viral/administração & dosagem , RNA Viral/genética , Saguinus/virologia , Animais , Doença Crônica , Modelos Animais de Doenças , Infecções por Flaviviridae/patologia , Infecções por Flaviviridae/virologia , Genoma Viral , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C Crônica/etiologia , Hepatite Viral Animal/patologia , Hepatite Viral Animal/virologia , Humanos , Fígado/patologia , Dados de Sequência Molecular , Mutação , Fatores de TempoRESUMO
The recent finding of a novel Epstein-Barr virus-related lymphocryptovirus (CalHV-3) in a captive colony of common marmoset (Callithrix jacchus) in the United States modifies the view that the host range of lymphocryptovirus is restricted to humans and Old World primates. We investigated the presence of Epstein-Barr virus-related viruses in 79 samples of New World monkeys caught in the wild, including six species of the Cebidae family and one of the Callitrichidae, living in the rain forest of French Guiana. Using a degenerate consensus PCR method for the herpesvirus DNA polymerase gene, we identified three novel lymphocryptoviruses from golden-handed tamarin (Saguinus midas) of the Callitrichidae family and squirrel monkey (Saimiri sciureus) and white-faced saki (Pithecia pithecia) of the Cebidae family. With the CalHV-3 strain, these three novel viruses constitute a well-supported phylogenetic clade in the Lymphocryptovirus genus, which is clearly distinct from the lineage of Old World lymphocryptovirus, hosted by catarrhine monkeys and humans. In tamarins, the prevalence of the novel lymphocryptovirus was more than 50%, indicating that it circulates well in the wild population, perhaps due to specific ecoethological patterns such as confrontations and intergroup migration. The detection and partial molecular characterization of the polymerase gene of three novel Gamma-1-Herpesvirinae from New World monkeys caught in the wild clearly indicate that free-ranging populations of platyrrhine are natural hosts of lymphocryptoviruses. Further characterization of these novel viruses will provide new insight not only into the origin and evolution of Gammaherpesvirinae but also into their pathogenicity.
Assuntos
Cebidae/virologia , Herpesviridae/isolamento & purificação , Saguinus/virologia , Saimiri/virologia , Animais , Sequência de Bases , Primers do DNA , Guiana Francesa , Herpesviridae/classificação , Dados de Sequência MolecularRESUMO
Clinical isolates of hepatitis A virus (HAV) replicate inefficiently in cell culture unless mutations are acquired throughout the genome. An Ala-to-Val substitution in the nonstructural protein 2B (2B-216) was known to have a major impact on replication in cell culture. Analysis of chimeric viruses confirmed that the 2B-A[216]V change was critical for efficient replication and that Leu or Ile could substitute for Val. Viruses containing Val, Ile, or Leu at 2B-216 all replicated with similar kinetics in cell culture, whereas the virus containing Ala at this position grew 10- to 20-fold less efficiently. In contrast, in vivo, virus with either Ala or Val at 2B-216 replicated equally efficiently when tested in a chimpanzee and in tamarins, and each amino acid was stably maintained. Attempts to complement wild-type 2B in trans with adapted 2B provided by co-infection with a second viable HAV mutant failed to enhance replication of the virus containing the wild-type 2B sequence.
Assuntos
Vírus da Hepatite A/genética , Vírus da Hepatite A/fisiologia , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Replicação Viral , Animais , Linhagem Celular , Genes Virais/genética , Engenharia Genética , Macaca mulatta/virologia , Mutação , Pan troglodytes/virologia , Fenótipo , Saguinus/virologia , Inoculações Seriadas , Proteínas não Estruturais Virais/genéticaRESUMO
An experimental hepatitis A virus (HAV) transmission study was performed in 3 tamarins, using a factor VIII concentrate linked to a recent outbreak of HAV infections in German hemophiliacs. The typical indicators for HAV infection were investigated in feces and serum samples. One tamarin showed a classical HAV infection with seroconversion. HAV antigen and HAV RNA were detected in feces of a second animal, but no seroconversion was observed until 19 weeks after inoculation. The HAV sequences from the reverse-transcription- and polymerase chain reaction-positive samples of the 2 animals were identical to the deduced HAV sequences of the chain of infection (from plasma pool to final product to patients). The study results provide conclusive evidence of the presence of infectious HAV in coagulation factor concentrate. Because a number of HAV transmission episodes have been described for solely solvent/detergent-treated factor VIII preparations, continued use of these agents seems questionable.
Assuntos
Fator VIII/normas , Hepatite A/transmissão , Saguinus/virologia , Alanina Transaminase/sangue , Animais , Detergentes/farmacologia , Contaminação de Medicamentos , RNA Viral/análise , Solventes/farmacologia , EsterilizaçãoRESUMO
GB viruses A and B (GBV-A and GBV-B) are members of the Flaviviridae family and are isolated from tamarins injected with serum from a human hepatitis patient. Along with a related human virus, GB virus C, or alternatively, hepatitis G virus (GBV-C/HGV), the three viruses represent the GB agents. Of the three viruses, GBV-B has been proposed as a potential surrogate model for the study of hepatitis C virus (HCV) infections of humans. GBV-B is phylogenetically most closely related to HCV and causes an acute, self-resolving hepatitis in tamarins as indicated by an increase in alanine aminotransferase and changes in liver histology. Similarities between GBV-B and HCV are found at the nucleotide sequence level with the two viruses sharing 28% amino acid homology over the lengths of their open reading frames. Short regions have even higher levels of homology that are functionally significant as shown by the ability of the GBV-B NS3 protease to cleave recombinant HCV polyprotein substrates. The shared protease substrate specificities suggest that GBV-B may be useful in testing antiviral compounds for activity against HCV. Although there are numerous similarities between GBV-B and HCV, there are important differences in that HCV frequently causes chronic infections in people, whereas GBV-B appears to cause only acute infections. The acute versus chronic course of infection may point to important differences between the two viruses that, along with the numerous similarities, will make GBV-B in tamarins a good surrogate model for HCV.
Assuntos
Flaviviridae/genética , Flaviviridae/patogenicidade , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C/virologia , Hepatite Viral Humana/genética , Saguinus/virologia , Doença Aguda , Animais , Antivirais/farmacologia , Doença Crônica , Modelos Animais de Doenças , Hepatite Viral Humana/patologia , Hepatócitos , Humanos , Homologia de Sequência de AminoácidosRESUMO
Presently, the State of Ceará reports the largest percentage of human rabies cases originated from wild animals in Brazil, transmitted by the principal simian species, the tamarin (Callithrix jacchus), found in various locations throughout the State, but concentrated along the coast. Epidemiological studies indicated that possibly the same virus caused the deaths in humans and non-human primates. This rabies virus seem to be different from all other identified so far.
Assuntos
Humanos , Animais , Vírus da Raiva/classificação , Saguinus/virologia , Brasil , Doenças dos Macacos/virologia , Vírus da Raiva/isolamento & purificação , Raiva/transmissão , Raiva/veterináriaRESUMO
Presently, the State of Ceará reports the largest percentage of human rabies cases originated from wild animals in Brazil, transmitted by the principal simian species, the tamarin (Callithrix jacchus), found in various locations throughout the State, but concentrated along the coast. Epidemiological studies indicated that possibly the same virus caused the deaths in humans and non-human primates. This rabies virus seem to be different from all other identified so far.
Assuntos
Doenças dos Macacos/virologia , Vírus da Raiva/classificação , Saguinus/virologia , Animais , Brasil , Humanos , Raiva/transmissão , Raiva/veterinária , Vírus da Raiva/isolamento & purificaçãoRESUMO
A-2 plaque virus (A2 virus) was originally isolated from the icteric-phase sera of US servicemen with viral hepatitis in the 1960s, but apart from a preliminary characterization little is known about the agent. We have now successfully cloned and sequenced the complete viral genome. A2 viral RNA consists of 7312 nucleotides, excluding the 62 nucleotide poly(A) tract at the 3' end, with one large open reading frame. Although clearly a member of the Picornaviridae, there is low homology to the available sequences, suggesting it is only loosely related to the classic rhino/enterovirus genus. In addition, there was no reactivity with group specific monoclonal antibody blends against polioviruses, enteroviruses 70 and 71, coxsackievirus B, and echoviruses. Two tamarins were inoculated with A2 virus to study viral pathogenesis. Both animals that received A2 virus became transiently viremic 1 week after the infection, as determined by RT-PCR, and they developed an antibody response to A2 virus. However, no physical signs or biochemical abnormalities, including elevated liver transaminases, were observed. In addition, no liver samples from patients with fulminant hepatitis (n = 7) or controls (n = 7) were positive for A2 viral RNA nor was anti-A2 neutralizing antibody detected in sera from hepatitis patients (n = 14), healthy laboratory donors (n = 14), or US blood donors (n = 33); however, most sera contained antibodies reactive with A2 virus proteins. These results suggest that A2 virus is a new member of the Picornaviridae but that its pathogenicity in nonhuman primates and association with human disease still need to be determined.
Assuntos
Genoma Viral , Picornaviridae/genética , Picornaviridae/imunologia , Anemia Aplástica/imunologia , Anemia Aplástica/virologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos/imunologia , Chlorocebus aethiops , Clonagem Molecular , Enterovirus/genética , Enterovirus/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite Viral Humana/imunologia , Hepatite Viral Humana/virologia , Hepatovirus/genética , Hepatovirus/imunologia , Humanos , Fígado/patologia , Fígado/virologia , Dados de Sequência Molecular , Testes de Neutralização , Filogenia , Picornaviridae/química , Picornaviridae/classificação , Infecções por Picornaviridae/imunologia , Infecções por Picornaviridae/virologia , RNA Viral/análise , RNA Viral/genética , Saguinus/imunologia , Saguinus/virologia , Células Vero , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/imunologiaRESUMO
Sera from eight different non-human primate species, in total 216 samples, were analysed for the presence of TT virus (TTV) sequences. A very high incidence of TTV infection was found in sera from both common chimpanzees and pygmy chimpanzees, 48.8% and 66.7%, respectively. Sequence analysis of PCR fragments from two pygmy chimpanzees and seven common chimpanzees resulted in a total of 14 different TTV sequences. Phylogenetic analysis, including human TTV of all known genotypes, revealed that: (i) TTV from pygmy chimpanzees are closely related to viruses from human genotypes 2 and 3; (ii) TTV sequences obtained from common chimpanzees cluster together with human TTV genotypes 5 and 6, the latter only at the protein level; (iii) TTV from the common chimpanzee subspecies Pan troglodytes verus and Pan troglodytes schweinfurthii cluster together, suggesting an ancient host-pathogen relationship before subspeciation 1.6 million years ago; and (iv) TTV of common and pygmy chimpanzees may have been acquired by these animals in different zoonotic events not longer than 2.5 million years ago.