Interferon Gamma and EV71-specific Antibody Reduce the Lethality of Enterovirus 71-infected Mice

碩士 === 國立成功大學 === 微生物及免疫學研究所 === 97 === Enterovirus 71 (EV71) infection induces fatal aseptic meningitis, encephalitis, and acute flaccid paralysis, with cardiopulmonary complications, particularly in infants and young children. Unfortunately, the pathogenesis of EV71 infection remains elusive, and...

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Main Authors: Shih-ping Chang, 張時斌
Other Authors: Shun-hua Chen
Format: Others
Language:zh-TW
Published: 2009
Online Access:http://ndltd.ncl.edu.tw/handle/78227235627316882884
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spelling ndltd-TW-097NCKU03800162015-11-20T04:19:09Z http://ndltd.ncl.edu.tw/handle/78227235627316882884 Interferon Gamma and EV71-specific Antibody Reduce the Lethality of Enterovirus 71-infected Mice γ-干擾素及腸病毒七十一型專一性抗體降低腸病毒七十一型感染小鼠的死亡率 Shih-ping Chang 張時斌 碩士 國立成功大學 微生物及免疫學研究所 97 Enterovirus 71 (EV71) infection induces fatal aseptic meningitis, encephalitis, and acute flaccid paralysis, with cardiopulmonary complications, particularly in infants and young children. Unfortunately, the pathogenesis of EV71 infection remains elusive, and vaccines and anti-viral drugs are not available. Clinical reports have shown a significant elevation of interferon gamma (IFN-γ) in the serum and cerebrospinal fluid of EV71-infected patients with fatal symptoms. The level of IFN-γ was reduced in patients after intravenous immunoglobulin treatment. The role of IFN-γ in EV71 infection is still unclear. We therefore used a mouse model to address this issue. Results showed that the level of IFN-γ was elevated in the brains of infected wild-type mice, which is in agreement with the findings of infected patients. To investigate the role of IFN-γ in EV71 infection, we infected mice deficient in IFN-γ receptor 1 (IFN-γR1-/-). We found that after infection, both the mortality and disease severity of IFN-γR1-/- mice were significantly higher than those of wild-type mice. High viral loads were also found in the tissues of IFN-γR1-/- mice. Further study showed that, the numbers of CD4 and CD8 T lymphocytes and macrophages in the spleens of IFN-γR1-/- mice were reduced. Moreover, IFN-γ treatment significantly reduced EV71 replication in a mouse neuronal cell line. Besides investigating the role of IFN-γ in EV71 infection, we also tested the therapeutic effect of EV71-specific antibody because EV71-specific antibody given before infection is shown to prevent EV71-infected mice from death by reducing tissue viral loads. Here we found that EV71-specific antibody treatment given after infection significantly reduced the mortality and disease severity of lymphocyte-deficient mice, which are highly susceptible to EV71 infection, by reducing tissue viral loads. In addition, both the neutralizing titer and the therapeutic efficacy of EV71-specific antibody were higher than those of intravenous immunoglobulin, which is now used in the clinic to treat EV71-infected patients. Collectively, our results show that IFN-γ induced after infection functions to reduce the viral loads in tissues by increasing the numbers of CD4 and CD8 T lymphocytes and macrophages and by reducing viral replication in neuronal cells. Our results also show the potential of using EV71-specific antibody to treat EV71-infected patients. Shun-hua Chen 陳舜華 2009 學位論文 ; thesis 42 zh-TW
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description 碩士 === 國立成功大學 === 微生物及免疫學研究所 === 97 === Enterovirus 71 (EV71) infection induces fatal aseptic meningitis, encephalitis, and acute flaccid paralysis, with cardiopulmonary complications, particularly in infants and young children. Unfortunately, the pathogenesis of EV71 infection remains elusive, and vaccines and anti-viral drugs are not available. Clinical reports have shown a significant elevation of interferon gamma (IFN-γ) in the serum and cerebrospinal fluid of EV71-infected patients with fatal symptoms. The level of IFN-γ was reduced in patients after intravenous immunoglobulin treatment. The role of IFN-γ in EV71 infection is still unclear. We therefore used a mouse model to address this issue. Results showed that the level of IFN-γ was elevated in the brains of infected wild-type mice, which is in agreement with the findings of infected patients. To investigate the role of IFN-γ in EV71 infection, we infected mice deficient in IFN-γ receptor 1 (IFN-γR1-/-). We found that after infection, both the mortality and disease severity of IFN-γR1-/- mice were significantly higher than those of wild-type mice. High viral loads were also found in the tissues of IFN-γR1-/- mice. Further study showed that, the numbers of CD4 and CD8 T lymphocytes and macrophages in the spleens of IFN-γR1-/- mice were reduced. Moreover, IFN-γ treatment significantly reduced EV71 replication in a mouse neuronal cell line. Besides investigating the role of IFN-γ in EV71 infection, we also tested the therapeutic effect of EV71-specific antibody because EV71-specific antibody given before infection is shown to prevent EV71-infected mice from death by reducing tissue viral loads. Here we found that EV71-specific antibody treatment given after infection significantly reduced the mortality and disease severity of lymphocyte-deficient mice, which are highly susceptible to EV71 infection, by reducing tissue viral loads. In addition, both the neutralizing titer and the therapeutic efficacy of EV71-specific antibody were higher than those of intravenous immunoglobulin, which is now used in the clinic to treat EV71-infected patients. Collectively, our results show that IFN-γ induced after infection functions to reduce the viral loads in tissues by increasing the numbers of CD4 and CD8 T lymphocytes and macrophages and by reducing viral replication in neuronal cells. Our results also show the potential of using EV71-specific antibody to treat EV71-infected patients.
author2 Shun-hua Chen
author_facet Shun-hua Chen
Shih-ping Chang
張時斌
author Shih-ping Chang
張時斌
spellingShingle Shih-ping Chang
張時斌
Interferon Gamma and EV71-specific Antibody Reduce the Lethality of Enterovirus 71-infected Mice
author_sort Shih-ping Chang
title Interferon Gamma and EV71-specific Antibody Reduce the Lethality of Enterovirus 71-infected Mice
title_short Interferon Gamma and EV71-specific Antibody Reduce the Lethality of Enterovirus 71-infected Mice
title_full Interferon Gamma and EV71-specific Antibody Reduce the Lethality of Enterovirus 71-infected Mice
title_fullStr Interferon Gamma and EV71-specific Antibody Reduce the Lethality of Enterovirus 71-infected Mice
title_full_unstemmed Interferon Gamma and EV71-specific Antibody Reduce the Lethality of Enterovirus 71-infected Mice
title_sort interferon gamma and ev71-specific antibody reduce the lethality of enterovirus 71-infected mice
publishDate 2009
url http://ndltd.ncl.edu.tw/handle/78227235627316882884
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