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1.
Vaccine ; 38(8): 2034-2044, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31982260

RESUMO

Enterovirus type 71 (EV71) and coxsackievirus A 16 (CA16) are recognized as the major pathogens responsible for human hand-foot-mouth disease. To develop a bivalent EV71-CA16 vaccine, rhesus macaques immunized with two doses of this vaccine via the intradermal route were challenged with EV71 or CA16, and their clinical symptoms, viral shedding, neutralizing antibodies, IFN-γ-specific ELISpots, and tissue viral load were examined longitudinally. Specific immunity against EV71 and CA16 was observed in the macaques, which exhibited controlled proliferation of the EV71 and CA16 viruses and upregulated expression of immune-related genes compared with the controls. Furthermore, broad protection against EV71 and CA16 challenge without immunopathological effects was observed in all the immunized macaques. These studies suggest that the bivalent EV71-CA16 inactivated vaccine was effective against wild-type EV71 or CA16 viral challenge in rhesus macaques.

2.
Lab Invest ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31857694

RESUMO

Enterovirus A71 (EV-A71) infection is primarily responsible for fatal hand, foot, and mouth disease (HFMD) cases. Infants and younger children are more likely to suffer central nervous system damage as a result of EV-A71 infection, but this virus mostly does not affect older children and adults. This study investigated the possible mechanism underlying the age-dependent lethal effect of EV-A71 infection by comparing neonatal and adult mouse models of EV-A71 infection. Although viral proliferation is absent in both neonatal and adult mice, we observed that EV-A71, as a stimulus for astrocytes, elevates the levels of cytokines and monoamine neurotransmitters in neonatal mice. Then, we selected IL-6 and adrenaline as targets in a pharmacological approach to further validate the roles of these factors in mediating the mortality of neonatal mice after EV-A71 infection. Intracerebral injection of IL-6 and adrenaline enhanced the severity of EV-A71 infection, while treatment with an anti-IL-6-neutralizing antibody or the adrenergic-antagonist phenoxybenzamine reversed the lethal effect of EV-A71 in neonatal mice. These results suggest that the central nervous system (CNS) damage in neonatal cases of EV-A71 infection might be caused by an activated fetal cerebral immune response to the virus, including the disruption of brainstem function through increased levels of cytokines and neurotransmitters, rather than the typical cytopathic effect (CPE) of viral infection.

4.
Clin Infect Dis ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31734699

RESUMO

BACKGROUND: Evaluation of a licensed inactivated EV71 vaccine is needed in a phase IV study with a large population to identify its effectiveness and safety for further application. METHODS: An open-label and controlled trial involving a large population of 155,995 children aged 6-71 months is performed; 40,724 were enrolled in the vaccine group and received 2 doses of inactivated EV71 vaccine at an interval of 1 month, and the remaining children were used as the control group. The EV71-infected hand, foot and mouth disease (HFMD) cases were monitored in the vaccine and control groups during a follow-up period of 14 months since the 28th days post inoculation through the local database of Notifiable Infectious Diseases Network. The effectiveness of the vaccine was estimated by comparing the incidence density in the vaccine group versus that in the control group based upon EV71 infected patients identified via laboratory testing. In parallel, the active and passive surveillance for safety of the vaccine was conducted by home or telephone visits and by using the Adverse Event Following Immunization (AEFI) system, respectively. RESULTS: An overall level of 89.7% (95% confidence interval [CI], 24.0 to 98.6) vaccine effectiveness (VE) against EV71 infection and a 4.58% rate of reported AEs were observed. Passive surveillance demonstrated a 0.31% rate of reported common minor reactions. CONCLUSIONS: The clinical protection and safety of the EV71 vaccine were demonstrated in the immunization of a large population. CLINICAL TRIALS REGISTRATION: NCT03001986.

5.
Virol Sin ; 34(6): 673-687, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31506828

RESUMO

Herpes simplex virus 1 (HSV-1), a member of α herpesviruses, shows a high infectivity rate of 30%-60% in populations of various ages. Some herpes simplex (HSV) vaccine candidates evaluated during the past 20 years have not shown protective efficacy against viral infection. An improved understanding of the immune profile of infected individuals and the associated mechanism is needed. HSV uses an immune evasion strategy during viral replication, and various virus-encoded proteins, such as ICP47 and Vhs, participate in this process through limiting the ability of CD8+ cytotoxic T lymphocytes to recognize target cells. Other proteins, e.g., Us3 and Us5, also play a role in viral immune evasion via interfering with cellular apoptosis. In this work, to study the mechanism by which HSV-1 strain attenuation interferes with the viral immune evasion strategy, we constructed a mutant strain, M5, with deletions in the Us3 and Us5 genes. M5 was shown to induce higher neutralizing antibody titers and a stronger cellular immune response than our previously reported M3 strain, and to prevent virus infection more effectively than the M3 strain in an in vivo mouse challenge test.

6.
Viruses ; 11(8)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31443275

RESUMO

Herpes simplex virus type 1 (HSV-1), one of the human pathogens widely epidemic and transmitted among various groups of people in the world, often causes symptoms known as oral herpes or lifelong asymptomatic infection. HSV-1 employs many sophisticated strategies to escape host antiviral immune response based on its multiple coding proteins. However, the functions involved in the immune evasion of miRNAs encoded by HSV-1 during lytic (productive) infection remain poorly studied. Dual-luciferase reporter gene assay and bioinformatics revealed that Asp-Glu-Ala-Asp (DEAD)-box helicase 41 (DDX41), a cytosolic DNA sensor of the DNA-sensing pathway, was a putative direct target gene of HSV-1-encoded miR-H2-3p. The transfection of miR-H2-3p mimics inhibited the expression of DDX41 at the level of mRNA and protein, as well as the expression of interferon beta (IFN-ß) and myxoma resistance protein I (MxI) induced by HSV-1 infection in THP-1 cells, and promoted the viral replication and its gene transcription. However, the transfection of miR-H2-3p inhibitor showed opposite effects. This finding indicated that HSV-1-encoded miR-H2-3p attenuated cytosolic DNA-stimulated antiviral immune response by manipulating host DNA sensor molecular DDX41 to enhance virus replication in cultured cells.

7.
NPJ Vaccines ; 4: 14, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30937186

RESUMO

Enterovirus type 71 (EV71) and coxsackievirus A 16 (CA16) are the major pathogens of human hand, foot, and mouth disease (HFMD). In our previous study, intramuscular immunization with the inactivated EV71 vaccine elicited effective immunity, while immunization with the inactivated CA16 vaccine did not. In this report, we focused on innate immune responses elicited by inactivated EV71 and CA16 antigens administered intradermally or intramuscularly. The distributions of the EV71 and CA16 antigens administered intradermally or intramuscularly were not obviously different, but the antigens were detected for a shorter period of time when administered intradermally. The expression levels of NF-κB pathway signaling molecules, which were identified as being capable of activating DCs, ILCs, and T cells, were higher in the intradermal group than in the intramuscular group. Antibodies for the EV71 and CA16 antigens colocalized with ILCs and DCs in skin and muscle tissues under fluorescence microscopy. Interestingly, ILC colocalization decreased over time, while DC colocalization increased over time. ELISpot analysis showed that coordination between DCs and ILCs contributed to successful adaptive immunity against vaccine antigens in the skin. EV71 and/or CA16 antigen immunization via the intradermal route was more capable of significantly increasing neutralizing antibody titers and activating specific T cell responses than immunization via the intramuscular route. Furthermore, neonatal mice born to mothers immunized with the EV71 and CA16 antigens were 100% protected against wild-type EV71 or CA16 viral challenge. Together, our results provide new insights into the development of vaccines for HFMD.

8.
J Infect Dis ; 219(1): 50-58, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30085178

RESUMO

Background: Mumps vaccine immunizations have reduced the incidence of this disease. With the variation of mumps circulating strain, novel vaccine strains are always important. Methods: A 2-center parallel, randomized, double-blind noninferiority trial was performed to compare an F-genotype attenuated mumps vaccine (SP strain) to the A-genotype vaccine (S-79, Jeryl-Lynn strain) in 1080 healthy children aged 8-24 months in Hubei, China. Results: Participants were randomly assigned to receive a high or low dose of the SP or S79 vaccine and then assessed clinically at 30 minutes and 1-28 days postinoculation. No differences in local or systemic reactivity were observed. A similar incidence of severe adverse events associated with the vaccine was observed in the high-dose group and the positive control group. Based on throat swab collections, no viral shedding was present at the 4th and 10th days in any group. Neutralizing and hemagglutination-inhibiting antibody assays with the F- or A-genotype strains showed similar trends in geometric mean titers in the high-dose SP and S79 groups. Increased cytotoxic T lymphocyte responses were observed in all groups. Conclusions: The F-genotype attenuated mumps vaccine is safe, offers immunogenicity against a homologous virus, and is noninferior to the A-genotype vaccine in 8- to 24-month-old children.


Assuntos
Vacina contra Caxumba/administração & dosagem , Vírus da Caxumba/imunologia , Caxumba/prevenção & controle , Anticorpos Antivirais/sangue , Pré-Escolar , China/epidemiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Genótipo , Testes de Inibição da Hemaglutinação , Humanos , Imunização , Lactente , Masculino , Caxumba/imunologia , Vacina contra Caxumba/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
9.
Viruses ; 10(5)2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29724057

RESUMO

Herpes simplex virus type 1(HSV-1) presents a conundrum to public health worldwide because of its specific pathogenicity and clinical features. Some experimental vaccines, such as the recombinant viral glycoproteins, exhibit the viral immunogenicity of a host-specific immune response, but none of these has achieved a valid epidemiological protective efficacy in the human population. In the present study, we constructed an attenuated HSV-1 strain M3 through the partial deletion of UL7, UL41, and the latency-associated transcript (LAT) using the CRISPR/Cas9 system. The mutant strain exhibited lowered infectivity and virulence in macaques. Neutralization testing and ELISpot detection of the specific T-cell responses confirmed the specific immunity induced by M3 immunization and this immunity defended against the challenges of the wild-type strain and restricted the entry of the wild-type strain into the trigeminal ganglion. These results in rhesus macaques demonstrated the potential of the attenuated vaccine for the prevention of HSV-1 in humans.


Assuntos
Antígenos Virais/imunologia , Herpes Simples/prevenção & controle , Herpesvirus Humano 1/genética , Vacinas contra Herpesvirus/imunologia , Animais , Antígenos Virais/genética , Sistemas CRISPR-Cas , Herpes Simples/imunologia , Vacinas contra Herpesvirus/genética , Imunogenicidade da Vacina , Macaca mulatta/virologia , Mutação , Testes de Neutralização , Fenótipo , Gânglio Trigeminal/virologia , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologia , Replicação Viral
10.
Front Microbiol ; 8: 1958, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29062310

RESUMO

Herpes simplex virus 1 (HSV1) is an important pathogen with a worldwide epidemic trend that affects populations of various ages. It has a high morbidity, particularly in juveniles, but a successful HSV1 vaccine is not currently available. Thus, our study systematically observed the immune responses induced in mice immunized with the attenuated HSV1 M3 mutant strain, which has mutations in the genes encoding the UL7 and Vhs tegument proteins and the latency-associated transcript. The immunity induced by the M3 mutant strain can control acute viral infection during HSV1 wild-type strain infection. Moreover, this immunity exerts a potent effect on controlling viral entry into the trigeminal neurons. These data encourage further studies investigating the development of M3 as a potential vaccine candidate, and much work is necessary to evaluate the safety and improve the immunogenicity of this strain.

11.
Virol Sin ; 32(5): 404-414, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28971351

RESUMO

We previously constructed a herpes simplex virus 1 (HSV-1) UL7 mutant virus (M1) and showed that a partial deletion mutation of the UL7 gene led to a lower proliferative rate and an attenuated phenotype. Using the M1 mutant, we further modified the UL41 gene, which encodes another tegument protein, and the latency-associated transcript (LAT) gene. Observations of the resulting mutants with modified UL7 and UL41 (M2) or UL7, UL41 and LAT (M3) genes indicated attenuated phenotypes, with lower proliferative ratios in various cells, non-lethal infections in mice and lower viral loads in nervous tissues compared with the wild-type strain. Furthermore, no LAT stable intron could be detected in the trigeminal ganglion of M3-infected animals. The results obtained with the three HSV-1 mutants indicate that the M3 mutant is an attenuated strain with low pathogenicity during both acute and latent infections. Together, the results support the use of the M3 mutant as a candidate for the development of an HSV-1 vaccine.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Herpesvirus Humano 1/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Animais , Linhagem Celular , Linhagem Celular Tumoral , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Células HEK293 , Humanos , Imuno-Histoquímica , Hibridização In Situ , Íntrons/genética , Camundongos , Camundongos Endogâmicos BALB C , Mutação/genética , Tecido Nervoso/metabolismo , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Gânglio Trigeminal/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-28540257

RESUMO

Enterovirus 71 (EV71) is one of the main pathogens responsible for hand, foot, and mouth disease (HFMD). Infection with EV71 can lead to severe clinical disease via extensive infections of either the respiratory or alimentary tracts in children. Based on the previous pathological study of EV71 infections in neonatal rhesus macaques, our work using this animal model and an EV71 chimera that expresses enhanced green fluorescent protein (EGFP-EV71) primarily explored where EV71 localizes and proliferates, and the subsequent initiation of the pathological process. The chimeric EGFP-EV71 we constructed was similar to the wild-type EV71 (WT-EV71) virus in its biological characteristics. Similar clinical manifestations and histo-pathologic features were equally displayed in neonatal rhesus macaques infected with either WT-EV71 or EGFP-EV71 via the respiratory route. Fluorescent signal tracing in tissues from the animals infected with EGFP-EV71 showed that EV71 proliferated primarily in the respiratory tract epithelium and the associated lymphoid tissues. Immunofluorescence and flow cytometry analyses revealed that EV71 was able to enter a pre-conventional dendritic cell (DC) population at the infection sites. The viremia identified in the macaques infected by WT-EV71 or EGFP-EV71 was present even in the artificial presence of a specific antibody against the virus. Our results suggest that EV71 primarily proliferates in the respiratory tract epithelium followed by subsequent entry into a pre-cDC population of DCs. These cells are then hijacked by the virus and they can potentially transmit the virus from local sites to other organs through the blood circulation during the infection process. Our results suggest that the EV71 infection process in this DC population does not interfere with the induction of an independent immune response against the EV71 infection in the neonatal macaques.


Assuntos
Células Dendríticas/virologia , Enterovirus Humano A/patogenicidade , Infecções por Enterovirus/veterinária , Infecções por Enterovirus/virologia , Interações Hospedeiro-Patógeno/fisiologia , Animais , Anticorpos Antivirais/sangue , Citocinas/sangue , Células Dendríticas/patologia , Modelos Animais de Doenças , Enterovirus Humano A/genética , Enterovirus Humano A/crescimento & desenvolvimento , Infecções por Enterovirus/diagnóstico por imagem , Infecções por Enterovirus/imunologia , Leucócitos Mononucleares , Macaca mulatta , Infecções Respiratórias/veterinária , Infecções Respiratórias/virologia , Carga Viral , Viremia/veterinária , Viremia/virologia
13.
Viruses ; 9(2)2017 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-28146109

RESUMO

As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1.Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post-infection,and viral latency-associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG)on day 365 post-infection. Neutralization testing and enzyme-linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues.


Assuntos
Modelos Animais de Doenças , Herpes Simples/patologia , Herpes Simples/virologia , Herpesvirus Humano 1/isolamento & purificação , Estruturas Animais/virologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , ELISPOT , Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Macaca mulatta , Testes de Neutralização , Linfócitos T/imunologia
14.
Virus Res ; 228: 90-101, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27890633

RESUMO

Hand, foot, and mouth disease (HFMD) mainly caused by Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) infections which presented significantly different clinical manifestations. Nevertheless, the factors underlying these differences remain unclear. Recently, the functions of microRNAs (miRNAs) in pathogen-host interactions have been highlighted. Here, we performed comprehensive miRNA profiling in EV71- and CA16-infected human bronchial epithelial (16HBE) cells at multiple time points using high-throughput sequencing. The results showed that 154 known and 47 novel miRNAs exhibited remarkable differences in expression. Of these, 65 miRNAs, including 58 known and 7 novel miRNAs, presented opposite trends in EV71- and CA16-infected samples. Subsequently, we mainly focused on the 56 known differentially expressed miRNAs by further screening for targets prediction. GO and pathway analysis of these targets demonstrated that 18 biological processes, 7 molecular functions, 1 cellular component and 123 pathways were enriched. Among these pathways, Cadherin signalling pathway, Wnt signalling pathway and angiogenesis showed significant alterations. The regulatory networks of these miRNAs with predicted targets, GOs, pathways and transcription factors were determined, which suggested that miRNAs displayed intricate regulatory mechanisms during the infection phase. Consequently, we specifically analysed the hierarchical GO categories of the predicted targets involved in adhesion. The results indicated that the distinct changes induced by EV71 and CA16 infection may be partly linked to airway epithelial barrier function. Taken together, our data provide useful insights that help elucidate the different host-pathogen interactions following EV71 and CA16 infection and might offer novel therapeutic targets for these infections.


Assuntos
Enterovirus Humano A/fisiologia , Infecções por Enterovirus/genética , Infecções por Enterovirus/virologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , MicroRNAs , Mucosa Respiratória/metabolismo , Mucosa Respiratória/virologia , Linhagem Celular , Biologia Computacional/métodos , Células Epiteliais , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Anotação de Sequência Molecular , Conformação de Ácido Nucleico , Interferência de RNA
15.
Virology ; 500: 198-208, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27829175

RESUMO

Coxsackievirus A16 (CV-A16) causes human hand, foot and mouth disease, but its pathogenesis is unclear. In rhesus macaques, CV-A16 infection causes characteristic vesicles in the oral mucosa and limbs as well as viremia and positive viral loads in the tissues, suggesting that these animals reflect the pathologic process of the infection. An immunologic analysis indicated a defective immune response, which included undetectable neutralizing antibodies and IFN-γ-specific memory T-cells in macaques infected with CV-A16. Furthermore, existing neutralizing antibodies in macaques immunized with the inactivated vaccine were surprisingly unable to protect against a viral challenge despite the presence of a positive T-cell memory response against viral antigens. The virus was capable of infecting pre-conventional dendritic cells and replicating within them, which may correlate with the immunological characteristics observed in the animals.


Assuntos
Enterovirus Humano A/fisiologia , Doença de Mão, Pé e Boca/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Células Dendríticas/imunologia , Células Dendríticas/virologia , Modelos Animais de Doenças , Enterovirus Humano A/genética , Enterovirus Humano A/patogenicidade , Doença de Mão, Pé e Boca/patologia , Doença de Mão, Pé e Boca/prevenção & controle , Doença de Mão, Pé e Boca/virologia , Humanos , Interferon gama/imunologia , Macaca mulatta , Testes de Neutralização , Linfócitos T/imunologia , Vacinas Virais/imunologia
16.
Virol J ; 13: 152, 2016 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-27618986

RESUMO

BACKGROUND: UL7, a tegument protein of Herpes Simplex Virus type I (HSV-1), is highly conserved in viral infection and proliferation and has an unknown mechanism of action. METHODS: A HSV-1 UL7 mutant (UL7-MU) was constructed using the CRISPR-cas9 system. The replication rate and plaque morphology were used to analyze the biological characteristics of the wild-type (WT), UL7-MU and MU-complemented P1 viruses. The virulence of the viruses was evaluated in mice. Real-time RT-qPCR and ChIP assays were used to determine the expression levels of relevant genes. RESULTS: The replication capacity of a recombinant virus (UL7-MU strain) was 10-fold lower than that of the WT strain. The neurovirulence and pathologic effect of the UL7-MU strain were attenuated in infected mice compared with the WT strain. In the latency model, the expression of latency-associated transcript (LAT) in the central nervous system (CNS) and trigeminal nerve was lower in UL7-MU-infected mice than in WT strain-infected mice. The transcription level of the immediate-early gene α-4 in UL7-MU-infected cells was reduced by approximately 2-fold compared with the clear transcriptional peak identified in WT strain-infected Vero cells within 7 h post-infection (p.i.). CONCLUSION: By modulating the transcription of the α-4 gene, UL7 may be involved in transcriptional regulation through its interaction with the transcript complex structure of the viral genome during HSV-1 infection.


Assuntos
Herpes Simples/virologia , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 1/patogenicidade , Proteínas Imediatamente Precoces/genética , Proteínas da Matriz Viral/genética , Animais , Regulação Viral da Expressão Gênica , Herpesvirus Humano 1/genética , Humanos , Proteínas Imediatamente Precoces/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteínas da Matriz Viral/metabolismo , Virulência
17.
Glob Pediatr Health ; 3: 2333794X16643723, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27336013

RESUMO

Hand, foot, and mouth disease (HFMD), with vesiculae on the hands, feet and mouth, is an infectious disease caused by many viral pathogens. However, the differences of immune response induced by these pathogens are unclear. We compared the clinical manifestations and the levels of immunologic indicators from 60 HFMD patients caused by different viral pathogens to analyze the differences in the immune response. It was shown that Th2 cytokines (IL-4 and IL-10) increased significantly in EV71-infected children; Th1 cytokines (IL-2 and IFN-γ) rose in CA16-infected children; both Th1 and Th2 cytokines elevated in non-EVG-infected children; only individual cytokines (such as IL-10) went up in EVG-infected children. Meanwhile, the antibodies induced by viral infection could not cross-interfere between the different pathogens. These differences might be due to variations in the immune response induced by the individual pathogens or to the pathogenesis of the infections by the individual pathogens.

18.
Artigo em Inglês | MEDLINE | ID: mdl-28066727

RESUMO

The pathological manifestations of fatal cases of human hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) are characterized by inflammatory damage to the central nervous system (CNS). Here, the dynamic distribution of EV71 in the CNS and the subsequent pathological characteristics within different regions of neonatal rhesus macaque brain tissue were studied using a chimeric EV71 expressing green fluorescence protein. The results were compared with brain tissue obtained from the autopsies of deceased EV71-infected HFMD patients. These observations suggested that the virus was prevalent in areas around the blood vessels and nerve nuclei in the brain stem and showed a preference for astrocytes in the CNS. Interestingly, infected astrocytes within the in vivo and in vitro human and macaque systems exhibited increased expression of excitatory neurotransmitters and cytokines that also stimulated the neuronal secretion of the excitatory neurotransmitters noradrenalin and adrenalin, and this process most likely plays a role in the pathophysiological events that occur during EV71 infection.


Assuntos
Astrócitos/virologia , Encéfalo/virologia , Enterovirus Humano A/fisiologia , Infecções por Enterovirus/virologia , Tropismo Viral , Animais , Animais Recém-Nascidos , Encéfalo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Enterovirus Humano A/crescimento & desenvolvimento , Enterovirus Humano A/isolamento & purificação , Epinefrina/metabolismo , Humanos , Macaca mulatta , Norepinefrina/metabolismo
19.
J Vet Med Sci ; 77(9): 1143-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25843743

RESUMO

Newcastle disease virus (NDV) causes a highly contagious viral disease in poultry and wild birds, and it can cause significant economic loss worldwide. Eight viral strains were isolated by inoculating embryonated chicken eggs from the Poyang Lake region of China with swab samples. All eight of the NDV isolates were identified as class I genotype 3 strains, but they diverged notablely from class II viruses. Further analysis revealed that all eight NDV isolates were lentogenic strains containing the (112)ERQER↓L(117) motif at the F protein cleavage site. The strains were highly identical and were more species specific (chicken and waterfowl) than site specific (Nanchang and Duchang regions). The close phylogenetic proximity of these isolates indicates that viral transmission may happen between poultry and wild birds. Our study demonstrates that lentogenic class I NDVs exist in clinically healthy wild waterfowl and poultry within the Poyang Lake region. Active surveillance of these viruses to determine their evolution and origin is one of the most realistic strategies for preventing and controlling NDV outbreaks.


Assuntos
Doença de Newcastle/virologia , Vírus da Doença de Newcastle/genética , Sequência de Aminoácidos , Animais , Animais Selvagens/virologia , Sequência de Bases , Aves/virologia , China/epidemiologia , Genes Virais/genética , Lagos , Dados de Sequência Molecular , Doença de Newcastle/epidemiologia , Vírus da Doença de Newcastle/isolamento & purificação , Filogenia
20.
Influenza Other Respir Viruses ; 8(6): 646-53, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25363159

RESUMO

Migrating wild birds are considered natural reservoirs of influenza viruses and serve as a potential source of novel influenza strains in humans and livestock. During routine avian influenza surveillance conducted in eastern China, a novel H5N8 (SH-9) reassortant influenza virus was isolated from a mallard duck in China. blast analysis revealed that the HA, NA, PB1, PA, NP, and M segments of SH-9 were most closely related to the corresponding segments of A/duck/Jiangsu/k1203/2010 (H5N8). The SH-9 virus preferentially recognized avian-like influenza virus receptors and was highly pathogenic in mice. Our results suggest that wild birds could acquire the H5N8 virus from breeding ducks and spread the virus via migratory bird flyways.


Assuntos
Patos/virologia , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/patogenicidade , Influenza Aviária/virologia , Animais , China , Feminino , Vírus da Influenza A/classificação , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , RNA Viral/genética , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Vírus Reordenados/patogenicidade , Análise de Sequência de DNA , Análise de Sobrevida , Proteínas Virais/genética
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