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Therapeutic intervention for poxviruses.

机译：痘病毒的治疗干预。

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摘要

Smallpox vaccination is associated with a high risk of adverse reactions. Currently, only Vaccinia immunoglobulin (VIG) is approved for use to treat complications but is contraindicated in the event of corneal involvement (Vaccinia virus keratitis; VACVK). Evaluation of other treatments has been complicated by the lack of a well-characterized animal model of VACVK.;We conducted the most complete analysis of the course of VACVK in rabbits presented to date. The clinical course of the disease paralleled that seen in humans, and the severity of the disease exhibited a dose response relative to the amount of the virus inoculum. We determined that an inoculum of 10 5 pfu is optimal for studying VACVK in rabbits.;The clinical presentation of VACVK was similar to that of Herpes simplex virus keratitis, an immunopathologic disease. To determine if immune cells infiltrated VACV-infected corneas with similar kinetics as is seen with herpes, samples of infected and control eyes were stained for neutrophils, CD4+ cells, CD8+ cells, and B cells. All four cell types infiltrated the cornea and eyelids. The kinetics of infiltration were similar, but not identical to, infiltration during herpes infection, suggesting that the different cell types may play different roles in the pathology of VACVK.;We next compared the effects of different combinations of VIG, prednisolone acetate, and trifluridine on the course and severity of disease. We showed that treatment with VIG neither exacerbated corneal scarring nor improved the severity of VACVK. The inclusion of prednisolone acetate interfered with viral clearance and the therapeutic effect of other treatments. Trifluridine alone was the most effective treatment for VACVK.;Finally, we identified a novel antiviral peptide, EB, which inhibited Vaccinia virus entry at low concentrations. The EB peptide is the first identified non-antibody inhibitor of VACV entry.;The studies in this thesis have resulted in the development of a better model for studying Vaccinia ocular infection, shown that trifluridine alone is the optimal therapy for ocular Vaccinia infections and that steroids should not be used for therapy, and identified a novel inhibitor of Vaccinia virus entry.
机译：天花疫苗接种与不良反应的高风险相关。目前，仅牛痘免疫球蛋白（VIG）被批准用于治疗并发症，但在角膜受累的情况下被禁用（牛痘病毒性角膜炎； VACVK）。由于缺乏特征明确的VACVK动物模型，使其他治疗方法的评估变得复杂。我们迄今为止对兔子中VACVK的病程进行了最完整的分析。该疾病的临床过程与人类所见相似，并且该疾病的严重程度表现出相对于病毒接种量的剂量反应。我们确定10 5 pfu的接种量是研究兔VACVK的最佳方法。VACVK的临床表现与单纯性疱疹病毒性角膜炎（一种免疫病理性疾病）相似。为了确定免疫细胞是否以与疱疹相似的动力学浸润被VACV感染的角膜，对感染和对照眼的样本进行了中性粒细胞，CD4 +细胞，CD8 +细胞和B细胞染色。所有四种细胞类型都浸润了角膜和眼睑。疱疹感染过程中的浸润动力学相似但不完全相同，表明不同的细胞类型在VACVK的病理中可能起不同的作用。我们接下来比较了VIG，醋酸泼尼松龙和三氟吡啶的不同组合的作用关于疾病的病程和严重程度。我们显示，VIG治疗既不会加剧角膜瘢痕形成，也不会改善VACVK的严重程度。醋酸泼尼松龙的加入会干扰病毒清除和其他治疗方法的治疗效果。单独使用三氟吡啶是治疗VACVK的最有效方法。最后，我们确定了一种新型抗病毒肽EB，该肽在低浓度下可抑制痘苗病毒的进入。 EB肽是第一个被确认的VACV进入的非抗体抑制剂。;本论文的研究导致开发了一个更好的研究牛痘疫苗眼感染的模型，表明单独使用三氟哌啶是治疗牛痘疫苗的最佳疗法，并且类固醇不应该用于治疗，并确定了一种新的痘苗病毒进入抑制剂。

著录项

  • 作者

    Altmann, Sharon E.;

  • 作者单位

    The University of Wisconsin - Madison.;

  • 授予单位 The University of Wisconsin - Madison.;
  • 学科 Biology Microbiology.;Biology Virology.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 242 p.
  • 总页数 242
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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