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1.
PLoS Pathog ; 16(7): e1008677, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32649726

RESUMO

Pegiviruses frequently cause persistent infection (as defined by >6 months), but unlike most other Flaviviridae members, no apparent clinical disease. Human pegivirus (HPgV, previously GBV-C) is detectable in 1-4% of healthy individuals and another 5-13% are seropositive. Some evidence for infection of bone marrow and spleen exists. Equine pegivirus 1 (EPgV-1) is not linked to disease, whereas another pegivirus, Theiler's disease-associated virus (TDAV), was identified in an outbreak of acute serum hepatitis (Theiler's disease) in horses. Although no subsequent reports link TDAV to disease, any association with hepatitis has not been formally examined. Here, we characterized EPgV-1 and TDAV tropism, sequence diversity, persistence and association with liver disease in horses. Among more than 20 tissue types, we consistently detected high viral loads only in serum, bone marrow and spleen, and viral RNA replication was consistently identified in bone marrow. PBMCs and lymph nodes, but not liver, were sporadically positive. To exclude potential effects of co-infecting agents in experimental infections, we constructed full-length consensus cDNA clones; this was enabled by determination of the complete viral genomes, including a novel TDAV 3' terminus. Clone derived RNA transcripts were used for direct intrasplenic inoculation of healthy horses. This led to productive infection detectable from week 2-3 and persisting beyond the 28 weeks of study. We did not observe any clinical signs of illness or elevation of circulating liver enzymes. The polyprotein consensus sequences did not change, suggesting that both clones were fully functional. To our knowledge, this is the first successful extrahepatic viral RNA launch and the first robust reverse genetics system for a pegivirus. In conclusion, equine pegiviruses are bone marrow tropic, cause persistent infection in horses, and are not associated with hepatitis. Based on these findings, it may be appropriate to rename the group of TDAV and related viruses as EPgV-2.


Assuntos
Medula Óssea/virologia , Infecções por Flavivirus/veterinária , Hepatite Viral Animal/virologia , Doenças dos Cavalos/virologia , Animais , Flaviviridae , Infecções por Flavivirus/virologia , Cavalos
2.
PLoS One ; 15(5): e0232783, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369533

RESUMO

INTRODUCTION: Human pegivirus 1 (HPgV-1) is a single-stranded, positive-sense RNA virus belonging to the Flaviviridae family with limited cause-effect evidence of the causation of human diseases. However, studies have shown a potential beneficial impact of HPgV-1 coinfection in HIV disease progression. Human T lymphotropic virus-1 (HTLV-1) is a retrovirus known for causing diseases, especially in muscle and white blood cells, in approximately 5% of patients. Thus, this study aimed to investigate the potential effects of an HPgV-1 infection in patients carrying HTLV-1 in the state of Pará in the North Region of Brazil. METHODS: A group of HTLV-1 carriers was compared to healthy controls. Blood samples were collected, data from medical regards were collected, and a questionnaire was administered. HPgV-1 and HTLV-1 positivity was determined by quantitative polymerase chain reaction (qRT-PCR). The data were analyzed to correlate the effects of HPgV-1 coinfection in HTLV-1 carriers. RESULTS: A total of 158 samples were included in the study: 74 HTLV-1-positive patients (46,8%) and 84 healthy controls (53,2%). The overall HPgV-1 positivity rate was 7.6% (12/158), resulting in a prevalence of 5.4% (4/74) and 9.5% (8/84) in HTLV-1 carriers and healthy controls, respectively. No significant differences were found when comparing any clinical or demographic data between groups. CONCLUSION: This study indicated that the prevalence of HPgV-1 infection is low in HTLV-1 carriers in Belém, Pará, and probably does not alter the clinical course of HTLV-1 infection, however, further studies are still needed.


Assuntos
Coinfecção/complicações , Infecções por Flaviviridae/complicações , Infecções por HTLV-I/complicações , Adulto , Brasil/epidemiologia , Coinfecção/epidemiologia , Feminino , Flaviviridae/isolamento & purificação , Infecções por Flaviviridae/epidemiologia , Infecções por HTLV-I/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
3.
Emerg Microbes Infect ; 9(1): 485-495, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32100631

RESUMO

The second human pegivirus HPgV-2 is a novel blood-borne virus that is strongly associated with the hepatitis C virus (HCV) infection. However, the molecular evidence for their association as well as the natural history and tissue tropism of HPgV-2 remain to be elucidated. In this longitudinal study, a total of 753 patients including 512 HIV-1 and HCV co-infected patients were enrolled to characterize the natural history of HPgV-2 infection. Peripheral blood mononuclear cells (PBMCs) and liver biopsies were collected to determine the tissue tropism of HPgV-2 using immunohistochemical staining of the HPgV-2 antigen and in situ hybridization of HPgV-2 RNA. We documented both persistent HPgV-2 infection with the presence of HPgV-2 viral RNA and antibodies up to 4.6 years and resolved HPgV-2 infection, accompanied by a simultaneous decline of anti-HPgV-2 antibodies and clearance of HPgV-2 viremia. Furthermore, we observed the clearance of HCV, but not HPgV-2, by treatment with direct-acting antivirals (DAAs). Biochemical tests and pathological analyses did not reveal any indication of hepatic impairment caused by HPgV-2. HPgV-2 RNA and nonstructural antigen were detected in the lymphocytes, but not in the hepatocytes present in the liver biopsy samples. In addition, both positive- and negative-strand HPgV-2 RNAs were detected in PBMCs, especially in B cells. The present study is the first to provide evidence that HPgV-2 is a lymphotropic, but not a hepatotropic virus and that HPgV-2 replication is independent of HCV viremia. These new findings let us gain insights into the evolution and persistent infection of RNA viruses in humans.


Assuntos
Coinfecção , Flaviviridae/fisiologia , Hepacivirus/fisiologia , Replicação Viral , Infecções por Flaviviridae , HIV-1 , Hepatite C , Humanos , Leucócitos Mononucleares , Estudos Longitudinais , RNA Viral/genética , Viremia
4.
Viruses ; 12(2)2020 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-31991915

RESUMO

Ticks transmit a wide variety of pathogens including bacteria, parasites and viruses. Over the last decade, numerous novel viruses have been described in arthropods, including ticks, and their characterization has provided new insights into RNA virus diversity and evolution. However, little is known about their ability to infect vertebrates. As very few studies have described the diversity of viruses present in ticks from the Caribbean, we implemented an RNA-sequencing approach on Amblyomma variegatum and Rhipicephalus microplus ticks collected from cattle in Guadeloupe and Martinique. Among the viral communities infecting Caribbean ticks, we selected four viruses belonging to the Chuviridae, Phenuiviridae and Flaviviridae families for further characterization and designing antibody screening tests. While viral prevalence in individual tick samples revealed high infection rates, suggesting a high level of exposure of Caribbean cattle to these viruses, no seropositive animals were detected. These results suggest that the Chuviridae- and Phenuiviridae-related viruses identified in the present study are more likely tick endosymbionts, raising the question of the epidemiological significance of their occurrence in ticks, especially regarding their possible impact on tick biology and vector capacity. The characterization of these viruses might open the door to new ways of preventing and controlling tick-borne diseases.


Assuntos
Doenças dos Bovinos , Flaviviridae/isolamento & purificação , Ixodidae/virologia , Vírus de RNA/classificação , Vírus de RNA/isolamento & purificação , Rhipicephalus/virologia , Infestações por Carrapato/veterinária , Animais , Anticorpos Antivirais/sangue , Bovinos/imunologia , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/parasitologia , Suscetibilidade a Doenças , Flaviviridae/genética , Flaviviridae/imunologia , Genoma Viral , Martinica , Filogenia , Vírus de RNA/genética , Vírus de RNA/imunologia , RNA Viral/análise , RNA Viral/genética , Estudos Soroepidemiológicos , Infestações por Carrapato/imunologia , Índias Ocidentais
5.
Arch Virol ; 165(3): 619-626, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31965315

RESUMO

Human pegivirus 2 (HPgV-2) is a recently recognized pegivirus of the family Flaviviridae. To investigate the epidemic features of HPgV-2 circulating in the human immunodeficiency virus (HIV)-infected population, we tested for antibodies and viral RNA of HPgV-2 and hepatitis C virus (HCV) with retrospective plasma samples collected from 771 HIV infections with multiple risk behaviors in Honghe Prefecture of Yunnan Province. A total of 195 subjects (25.29%) were seroreactive to HPgV-2, and 41 (5.32%) were RNA positive. Although the positive rate of HPgV-2 antibodies in HIV/HCV-coinfected individuals (27.69%) was significantly higher than that of HIV monoinfections (20.82%) (p = 0.036), this is the first report of HPgV-2 viremia in HIV-infected individuals without HCV infection and the presence of two HPgV-2 lineages in China. Our data indicate that HPgV-2 can also be transmitted sexually, which might be facilitated when combined with HCV infection, injecting drug use, and risky sexual behavior, which appear to have a synergistic effect on HPgV-2 infection. Phylogenetic analysis of 26 near-full-length genome sequences showed that the HPgV-2 strains in China are divided into two clusters.


Assuntos
Infecções por Flaviviridae/complicações , Infecções por Flaviviridae/epidemiologia , Flaviviridae/classificação , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Viremia , Anticorpos Antivirais/sangue , China/epidemiologia , Humanos , Incidência , Filogenia , Prevalência , RNA Viral/genética , RNA Viral/isolamento & purificação
6.
Mol Cell ; 77(3): 542-555.e8, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-31810760

RESUMO

The RNA modification N6-methyladenosine (m6A) modulates mRNA fate and thus affects many biological processes. We analyzed m6A across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV). We found that infection by these viruses in the Flaviviridae family alters m6A modification of specific cellular transcripts, including RIOK3 and CIRBP. During viral infection, the addition of m6A to RIOK3 promotes its translation, while loss of m6A in CIRBP promotes alternative splicing. Importantly, viral activation of innate immune sensing or the endoplasmic reticulum (ER) stress response contributes to the changes in m6A in RIOK3 or CIRBP, respectively. Further, several transcripts with infection-altered m6A profiles, including RIOK3 and CIRBP, encode proteins that influence DENV, ZIKV, and HCV infection. Overall, this work reveals that cellular signaling pathways activated during viral infection lead to alterations in m6A modification of host mRNAs to regulate infection.


Assuntos
Adenosina/análogos & derivados , Infecções por Flaviviridae/genética , RNA Mensageiro/genética , Adenosina/genética , Linhagem Celular , Dengue/virologia , Vírus da Dengue/genética , Flaviviridae/genética , Hepacivirus/genética , Hepatite C/virologia , Interações Hospedeiro-Patógeno/genética , Humanos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Replicação Viral/genética , Zika virus/genética , Infecção por Zika virus/genética
7.
Virology ; 539: 69-79, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31689572

RESUMO

We applied an NGS based target capture approach to amplify HPgV-2 sequences from metagenomic libraries and enable full genome characterization. Despite expanded geographical sampling, sequence variability remains low, with diversity concentrated in approximately 3.3% of all amino acids. Serial samples from one HPgV-2 positive individual co-infected with comparable titers of HIV, HCV, and GBV-C showed that HPgV-2 remains highly stable over several weeks compared to other RNA viruses, despite a similarly error-prone polymerase. The consistent epidemiological association with and structural similarities to HCV, and the weak positive correlation of HCV and HPgV-2 titers shown here, suggests it may benefit from co-infection. While minimal selective pressure on HPgV-2 to evolve could suggest fitness, the rarity of HPgV-2 and the tight phylogenetic clustering of global strains likely indicates origination from a common source and a virus that is ill-suited to its host. Sporadic infections may explain the limited genetic diversity observed worldwide.


Assuntos
Flaviviridae/genética , Coinfecção/virologia , Flaviviridae/classificação , Infecções por Flaviviridae/virologia , Variação Genética , Genoma Viral/genética , Geografia , Hepatite C/virologia , Humanos , Filogenia , Vírus de RNA/genética , RNA Viral/genética , Análise de Sequência de RNA , Carga Viral , Proteínas Virais/genética
9.
Virol J ; 16(1): 132, 2019 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711510

RESUMO

BACKGROUND: Human pegivirus (HPgV) is structurally similar to hepatitis C virus (HCV) and was discovered 20 years ago. Its distribution, natural history and exact rule of this viral group in human hosts remain unclear. Our aim was to determine, by deep next-generation sequencing (NGS), the entire genome sequence of HPgV that was discovered in an Egyptian patient while analyzing HCV sequence from the same patient. We also inspected whether the co-infection of HCV and HPgV will affect the patient response to HCV viral treatment. To the best of our knowledge, this is the first report for a newly isolated HPgV in an Egyptian patient who is co-infected with HCV. CASE PRESENTATION: The deep Next Generation Sequencing (NGS) technique was used to detect HCV sequence in hepatitis C patient's plasma. The results revealed the presence of HPgV with HCV. This co-infection was confirmed using conventional PCR of the HPgV 5' untranslated region. The patient was then subjected to direct-acting-antiviral treatment (DAA). At the end of the treatment, the patient showed a good response to the HCV treatment (i.e., no HCV-RNA was detected in the plasma), while the HPgV-RNA was still detected. Sequence alignment and phylogenetic analyses demonstrated that the detected HPgV was a novel isolate and was not previously published. CONCLUSION: We report a new variant of HPgV in a patient suffering from hepatitis C viral infection.


Assuntos
Coinfecção/virologia , Infecções por Flaviviridae/virologia , Flaviviridae/genética , Flaviviridae/isolamento & purificação , Genoma Viral/genética , Hepacivirus/isolamento & purificação , Hepatite C/virologia , Adulto , Antivirais/uso terapêutico , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Egito , Infecções por Flaviviridae/diagnóstico , Infecções por Flaviviridae/tratamento farmacológico , Variação Genética , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Humanos , Masculino , Filogenia , RNA Viral/sangue , RNA Viral/genética , Resultado do Tratamento
10.
Oxid Med Cell Longev ; 2019: 1409582, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531178

RESUMO

Oxidative stress is induced once the balance of generation and neutralization of reactive oxygen species (ROS) is broken in the cell, and it plays crucial roles in a variety of natural and diseased processes. Infections of Flaviviridae viruses trigger oxidative stress, which affects both the cellular metabolism and the life cycle of the viruses. Oxidative stress associated with specific viral proteins, experimental culture systems, and patient infections, as well as its correlations with the viral pathogenesis attracts much research attention. In this review, we primarily focus on hepatitis C virus (HCV), dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and tick-borne encephalitis virus (TBEV) as representatives of Flaviviridae viruses and we summarize the mechanisms involved in the relevance of oxidative stress for virus-associated pathogenesis. We discuss the current understanding of the pathogenic mechanisms of oxidative stress induced by Flaviviridae viruses and highlight the relevance of autophagy and DNA damage in the life cycle of viruses. Understanding the crosstalk between viral infection and oxidative stress-induced molecular events may offer new avenues for antiviral therapeutics.


Assuntos
Dano ao DNA , Infecções por Flaviviridae/metabolismo , Flaviviridae/metabolismo , Estresse Oxidativo , Animais , Infecções por Flaviviridae/patologia , Infecções por Flaviviridae/terapia , Humanos
11.
Parasit Vectors ; 12(1): 450, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31511049

RESUMO

BACKGROUND: Alongshan virus (ALSV) is a novel discovered segmented flavivirus associated with human febrile illness in northeastern China. Ixodes persulcatus is considered as a candidate vector of ALSV in the endemic regions. However, the role of domesticated animals in the circulation and transmission of ALSV have not been investigated. To evaluate the prevalence of ALSV infections in domesticated animals, viral RNA and viral specific antibodies were detected in sheep and cattle in Hulunbuir of northeastern Inner Mongolia. The findings contribute to the understanding of the ecology and transmission of ALSV among different natural hosts. METHODS: A total of 480 animal serum samples were collected in Hulunbuir of northeastern China in May, 2017. Viral specific antibodies were tested by indirect enzyme-linked immunosorbent assay (ELISA) with a purified E. coli recombinant capsid protein (VP2) of ALSV (strain H3) and further detected by viral neutralization test (VNT). RNA in serum samples were extracted and detected for ALSV sequence by quantitative real-time RT-PCR. ALSV RNA positive samples were used for virus isolation. RESULTS: ALSV-specific antibodies were detected in 9.2% (22/240) of examined sheep and 4.6% (11/240) of examined cattle by ELISA, while lower serological positivity with 4.2% (10/240) for sheep and 1.7% (4/240) for cattle was confirmed by VNT. In contrast, the prevalence of ALSV RNA was much higher, ranging from 26.3% (63/240) in sheep to 27.5% (66/240) in cattle. The partial S1 (NS5-like) and S3 (NS3-like) segments of ALSVs in sheep and cattle shared high identities of more than 98% to the human and tick isolates in the studied regions. CONCLUSIONS: These results suggest that the natural infection of ALSV can be found in sheep and cattle in the endemic regions.


Assuntos
Anticorpos Antivirais/sangue , Doenças dos Bovinos/epidemiologia , Reservatórios de Doenças/virologia , Infecções por Flaviviridae/veterinária , Flaviviridae/isolamento & purificação , RNA Viral/sangue , Doenças dos Ovinos/epidemiologia , Animais , Bovinos , Doenças dos Bovinos/virologia , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Flaviviridae/genética , Flaviviridae/imunologia , Infecções por Flaviviridae/epidemiologia , Infecções por Flaviviridae/virologia , Testes de Neutralização , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Ovinos , Doenças dos Ovinos/virologia
12.
Biologicals ; 61: 1-7, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31447377

RESUMO

Horses are often used as blood donors for commercial horse serum (HS) production and to manufacture biologicals. HS is an alternative for fetal bovine serum (FBS) used as a supplement for cell culture and vaccine production. Furthermore, HS is also frequently obtained in order to produce antisera toxins and pathogens. The advent of high-throughput sequencing (HTS) has promoted changes in virus detection, since previous knowledge of targets is not required. Thus, the present study aimed to describe the virome of five different batches of commercial HS from New Zealand (three batches) and Brazil and the United States (one batch each) using HTS. Each HS pool were processed and sequenced using an Illumina MiSeq platform. Sequences-related to viruses belonging to the Flaviviridae, Herpesviridae, and Parvoviridae families were detected. Particularly, equine hepacivirus (EqHV), equine pegivirus (EPgV), and Theiler's disease-associated virus (TDAV) were more frequent found in the batches analyzed. The presence of viral genomes in cell culture sera illustrates that these commercial sera can contain a mixture of different viruses and, therefore, can be regarded as potentially infectious for susceptible hosts. Moreover, the innocuity of commercial HS is important for the efficiency and security of diagnostics and the production of biological products.


Assuntos
Flaviviridae/genética , Genoma Viral , Herpesviridae/genética , Cavalos/virologia , Parvoviridae/genética , Soro/virologia , Animais , Meios de Cultura , Flaviviridae/classificação , Herpesviridae/classificação , Cavalos/sangue , Parvoviridae/classificação
13.
Emerg Microbes Infect ; 8(1): 1265-1279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31469046

RESUMO

Since its genome details are publically available, the mosquito Aedes albopictus has become the central stage of attention for deciphering multiple biological and evolutionary aspects at the root of its success as an invasive species. Its genome of 1,967 Mb harbours an unusual high number of non-retroviral integrated RNA virus sequences (NIRVS). NIRVS are enriched in piRNA clusters and produce piRNAs, suggesting an antiviral effect. Here, we investigated the evolutionary history of NIRVS in geographically distant Ae. albopictus populations by comparing genetic variation as derived by neutral microsatellite loci and seven selected NIRVS. We found that the evolution of NIRVS was far to be neutral with variations both in their distribution and sequence polymorphism among Ae. albopictus populations. The Flaviviral elements AlbFlavi2 and AlbFlavi36 were more deeply investigated in their association with dissemination rates of dengue virus (DENV) and chikungunya virus (CHIKV) in Ae. albopictus at both population and individual levels. Our results show a complex association between NIRVS and DENV/CHIKV opening a new avenue for investigating the functional role of NIRVS as antiviral elements shaping vector competence of mosquitoes to arboviruses.


Assuntos
Aedes/genética , Evolução Molecular , Flaviviridae/genética , Genoma de Inseto , Mosquitos Vetores/genética , Aedes/imunologia , Aedes/virologia , Animais , Vírus Chikungunya/isolamento & purificação , Vírus da Dengue/isolamento & purificação , Mosquitos Vetores/imunologia , Mosquitos Vetores/virologia , RNA Interferente Pequeno/genética
14.
Biomed Res Int ; 2019: 5857285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31346520

RESUMO

Background: Flaviviridae viruses are single-stranded, positive-sense RNA viruses, which threat human constantly mediated by mosquitoes, ticks, and sandflies. Considering the recent increase in the prevalence of the family virus and its risk potential, we investigated the codon usage pattern to understand its evolutionary processes and provide some useful data to develop the medications for most of Flaviviridae viruses. Results: The overall extent of codon usage bias in 65 Flaviviridae viruses is low with the average value of GC contents being 50.5% and the highest value being 55.9%; the lowest value is 40.2%. ENC values of Flaviviridae virus genes vary from 48.75 to 57.83 with a mean value of 55.56. U- and A-ended codons are preferred in the Flaviviridae virus. Correlation analysis shows that the positive correlation between ENC value and GC content at the third nucleotide positions was significant in this family virus. The result of analysis of ENC, neutrality plot analysis, and correlation analysis revealed that codon usage bias of all the viruses was affected mainly by natural selection. Meanwhile, according to correspondence analysis (CoA) based on RSCU and phylogenetic analysis, the Flaviviridae viruses mainly are made up of two groups, Group I (Yellow fever virus, Apoi virus, Tembusu virus, Dengue virus 1, and others) and Group II (West Nile virus lineage 2, Japanese encephalitis virus, Usutu virus, Kedougou virus, and others). Conclusions: All in, the bias of codon usage pattern is affected not only by compositional constraints but also by natural selection. Phylogenetic analysis also illustrates that codon usage bias of virus can serve as an effective means of evolutionary classification in Flaviviridae virus.


Assuntos
Uso do Códon/genética , Evolução Molecular , Infecções por Flaviviridae/genética , Flaviviridae/genética , Animais , Composição de Bases/genética , Códon/genética , Biologia Computacional , Flaviviridae/classificação , Flaviviridae/patogenicidade , Infecções por Flaviviridae/virologia , Genoma Viral/genética , Humanos , Nucleotídeos/genética , Filogenia , Seleção Genética/genética
15.
Microbiol Immunol ; 63(10): 401-406, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342548

RESUMO

The family Flaviviridae comprises four genera, namely, Flavivirus, Pestivirus, Pegivirus, and Hepacivirus. These viruses have similar genome structures, but the genomes of Pestivirus and Flavivirus encode the secretory glycoproteins Erns and NS1, respectively. Erns plays an important role in virus particle formation and cell entry, whereas NS1 participates in the formation of replication complexes and virus particles. Conversely, apolipoproteins are known to participate in the formation of infectious particles of hepatitis C virus (HCV) and various secretory glycoproteins play a similar role in HCV particles formation, suggesting that there is no strong specificity for the function of secretory glycoproteins in infectious-particle formation. In addition, recent studies have shown that host-derived apolipoproteins and virus-derived Erns and NS1 play comparable roles in infectious-particle formation of both HCV and pestiviruses. In this review, we summarize the roles of secretory glycoproteins in the formation of Flaviviridae virus particles.


Assuntos
Apolipoproteínas/fisiologia , Infecções por Flaviviridae/virologia , Flaviviridae , Glicoproteínas/fisiologia , Vírion/fisiologia , Flaviviridae/patogenicidade , Flaviviridae/fisiologia , Interações entre Hospedeiro e Microrganismos , Humanos , Montagem de Vírus
16.
BMC Public Health ; 19(1): 685, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159757

RESUMO

BACKGROUND: Hepatitis G virus (HGV) infection transmitted from blood donors is a concern in China, as many articles about HGV infection in Chinese blood donors from different provinces have been published. This study aimed to evaluate the overall prevalence of HGV infection in Chinese blood donors and analyse the potential risk of HGV infection through blood transfusion in China. METHODS: We performed a literature search in PubMed, EMBASE, Web of Science, the Chinese BioMedical Literature Database (CBM) and the China National Knowledge Infrastructure (CNKI) up to October 2018 regarding the prevalence of HGV in Chinese blood donors. Eligibility assessment and data extraction were conducted independently by 2 researchers, and meta-analysis was performed to synthesize the data. Heterogeneity was evaluated using Cochran's Q test and quantified using the I2 statistic. Subgroup analyses were performed to identify the possible sources of heterogeneity. Publication bias was assessed using both funnel plot and Egger's tests. RESULTS: A total of 102 studies with 67,348 blood donors published from 1996 to 2016 and covering 26 provinces or municipalities were included for further analyses. The pooled prevalence of HGV was 3.91% (95%CI: 3.18-4.71%) by enzyme immune assay/enzyme linked immunosorbent assay (EIA/ELISA) and 3.25% (95%CI: 2.35-4.26%) by polymerase chain reaction (PCR). The prevalence of HGV may be significantly affected by region, province or municipality and potentially by the paid/voluntary status of the blood donors. No significant difference was found between plasma and full blood donation. CONCLUSIONS: The prevalence of HGV in blood donors from China was similar to that in blood donors from many other countries and higher than that of some other hepatitis viruses, such as hepatitis B virus. The risk of transfusion-transmitted HGV still exists after routine blood donor screening, especially in those patients coinfected with other hepatitis viruses and/or HIV. On the basis of our study, we may suggest adding HGV screening for blood transfusions in mainland China in the future.


Assuntos
Doadores de Sangue , Transfusão de Sangue , Vírus GB C , Hepatite Viral Humana/epidemiologia , Adulto , Doadores de Sangue/estatística & dados numéricos , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Flaviviridae , Hepatite Viral Humana/virologia , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , RNA Viral/sangue , Fatores de Risco , Adulto Jovem
17.
Int J Infect Dis ; 85: 111-113, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31170546

RESUMO

OBJECTIVES: To investigate the prevalence, risk factors, and genotypes of human pegivirus type 1 (HPgV-1) in hematopoietic stem cell transplantation (HSCT) patients. METHODS: One hundred and eighty-eight HSCT patients and 694 healthy blood donors were investigated retrospectively, including their demographic information and HPgV-1 infection status. RESULTS: When compared with healthy blood donors, a significantly higher HPgV-1 prevalence (18.6% vs. 2.3%) and a high risk of HPgV-1 infection (odds ratio 9.7) were observed in HSCT patients (p<0.05). The number of transfusions in patients with RNA test conversions (negative to positive) was significantly higher than the number in patients without conversions (negative to negative) (median 10 vs. 1) (p<0.05). Although HPgV-1 infection is independent of age, sex, blood type, hepatitis B virus infection, hepatitis C virus infection, marriage status, and type of hematological malignancy (p>0.05), race might be a risk factor for infection (p<0.05). The great majority (95.7%) of HPgV-1-positive patients were infected with genotype 3. CONCLUSIONS: HPgV-1 is highly prevalent in HSCT patients, and blood transfusions can significantly increase the risk of HPgV-1 infection. Thus, HPgV-1 screening is recommended in HSCT patients to reduce the potential impact of infection on survival, as well as in their blood and stem cell donors to reduce the risk of infection after transfusions, unless the beneficial effects of HPgV-1 infection in immunocompromised patients are clearly confirmed.


Assuntos
Infecções por Flaviviridae/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Adulto , Doadores de Sangue , Feminino , Flaviviridae/genética , Infecções por Flaviviridae/virologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
19.
Am J Epidemiol ; 188(9): 1586-1594, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31145443

RESUMO

Highly active antiretroviral therapy has revolutionized the battle against human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). From its current global rollout, HIV/AIDS morbidity and mortality has been greatly reduced, yet there exists substantial interest in the development of new therapies to further mitigate the HIV/AIDS health burden and to inhibit any fallout from the development of antiretroviral drug resistance. One potential intervention is the human pegivirus (HPgV). HPgV is not known to cause disease, and most remarkably it is shown to delay the progression of HIV to AIDS. However, the health benefit of increasing HPgV prevalence in the community of HIV-infected men remains unknown at the public health level. We evaluated the utility of HPgV biovaccination for mitigating the HIV/AIDS health burden using mathematical models. Importantly, our work considers the potential concern that HPgV will, itself, evolve to become disease-causing by permitting mutant disease-causing HPgV strains to potentially arise during treatment. Our findings show that HPgV biovaccination rates of 12.5%-50% annually could prevent 4.2-23.6 AIDS incidences and 3.3-18.8 AIDS deaths, and could save 2.9-18.6 disability-adjusted life years per 1,000 people. Together, these findings indicate that HPgV biovaccination could be an effective therapy for reducing HIV/AIDS morbidity and mortality, and thus warrants further exploration.


Assuntos
Síndrome de Imunodeficiência Adquirida/prevenção & controle , Infecções por Flaviviridae/complicações , Flaviviridae , Infecções por HIV/terapia , Síndrome de Imunodeficiência Adquirida/epidemiologia , Síndrome de Imunodeficiência Adquirida/mortalidade , Terapia Antirretroviral de Alta Atividade , Coinfecção , Progressão da Doença , Flaviviridae/genética , Infecções por HIV/complicações , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Homossexualidade Masculina , Humanos , Incidência , Masculino , Modelos Biológicos , Mutação
20.
N Engl J Med ; 380(22): 2116-2125, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31141633

RESUMO

BACKGROUND: In 2017, surveillance for tickborne diseases in China led to the identification of a patient who presented to a hospital in Inner Mongolia with a febrile illness that had an unknown cause. The clinical manifestation of the illness was similar to that of tickborne encephalitis virus (TBEV) infection, but neither TBEV RNA nor antibodies against the virus were detected. METHODS: We obtained a blood specimen from the index patient and attempted to isolate and identify a causative pathogen, using genome sequence analysis and electron microscopy. We also initiated a heightened surveillance program in the same hospital to screen for other patients who presented with fever, headache, and a history of tick bites. We used reverse-transcriptase-polymerase-chain-reaction (RT-PCR) and cell-culture assays to detect the pathogen and immunofluorescence and neutralization assays to determine the levels of virus-specific antibodies in serum specimens from the patients. RESULTS: We found that the index patient was infected with a previously unknown segmented RNA virus, which we designated Alongshan virus (ALSV) and which belongs to the jingmenvirus group of the family Flaviviridae. ALSV infection was confirmed by RT-PCR assay in 86 patients from Inner Mongolia and Heilongjiang who presented with fever, headache, and a history of tick bites. Serologic assays showed that seroconversion had occurred in all 19 patients for whom specimens were available from the acute phase and the convalescent phase of the illness. CONCLUSIONS: A newly discovered segmented virus was found to be associated with a febrile illness in northeastern China. (Funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China.).


Assuntos
Doenças Transmissíveis Emergentes/virologia , Flaviviridae/isolamento & purificação , Doenças Transmitidas por Carrapatos/virologia , Adulto , Idoso , Animais , China/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Fadiga/etiologia , Feminino , Febre/etiologia , Flaviviridae/classificação , Flaviviridae/genética , Flaviviridae/ultraestrutura , Cefaleia/etiologia , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Avaliação de Sintomas , Doenças Transmitidas por Carrapatos/complicações , Doenças Transmitidas por Carrapatos/epidemiologia , Carrapatos/virologia
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