Humanized mice in infectious diseases

The pathogenesis of infectious agents with human tropism can only be properly studied in an in vivo model featuring human cells or tissue. Humanized mice represent a small animal model featuring human cells or tissue that can be infected by human-specific viruses, bacteria, and parasites and also providing a functional human immune system. This makes the analysis of a human immune response to infection possible and allows for preclinical testing of new vaccines and therapeutic agents. Results of various studies using humanized mice to investigate pathogens with human tropism are presented in this review. In addition, the limitations of humanized mice and methods to improve this valuable animal model are discussed.     

A dynamic, optimal disease control model for foot-and-mouth disease: I. Model description

A dynamic optimization model was developed and used to evaluate alternative foot-and-mouth disease (FMD) control strategies. The model chose daily control strategies of depopulation and vaccination that minimized total regional cost for the entire epidemic duration, given disease dynamics and resource constraints. The disease dynamics and the impacts of control strategies on these dynamics were characterized in a set of difference equations; effects of movement restrictions on the disease dynamics were also considered. The model was applied to a three-county region in the Central Valley of California; the epidemic relationships were parameterized and validated using the information obtained from an FMD simulation model developed for the same region. The optimization model enables more efficient searches for desirable control strategies by considering all strategies simultaneously, providing the simulation model with optimization results to direct it in generating detailed predictions of potential FMD outbreaks.     

传染性造血器官坏死病毒-Sn1203株的基因型及糖蛋白的生物信息学分析

利用鲤(Cyprinus carpio)上皮细胞(epitheliaoma papulosum cyprini, EPC)培养传染性造血器官坏死病毒- Sn1203分离株(IHNV-Sn1203), 根据GenBank中IHNV G蛋白基因开放阅读框(open reading frame, ORF)的序列设计引物(GenBank序列编号AB288207), 采用RT-PCR的方法克隆得到IHNV-Sn1203株G蛋白全长ORF, 克隆至表达载体pET27b(+)中, 构建了pET27-G重组质粒, 并进行了测序分析。生物信息学分析结果显示, IHNV-Sn1203株G蛋白基因序列长度为1 527 bp, 与韩国株具有最高的核酸同源性(96.86%)和氨基酸同源性(97.05%)。该基因编码508个氨基酸残基, 推导分子量约为56.55 kD, 等电点为6.15; 氨基酸序列分析表明, G蛋白富含丝氨酸、苏氨酸和酪氨酸, 存在28个潜在的磷酸化位点; 存在4个潜在的N-糖基化位点和7个潜在的O-糖基化位点; G蛋白N端含有20个氨基酸的信号肽; 亲水性大于输水性; 位于483~508位氨基酸存在一跨膜区; 抗原表位预测显示抗原性良好; 系统进化树分析显示, IHNV-Sn1203株与日本株和韩国株聚为一簇, 都属于JRt基因型。

     

番茄不孕病毒BJ株系基因组测定与侵染性克隆

番茄不孕病毒(Tomato aspermy virus,TAV)可侵染包括藜科(Chenopodiaceae)、茄科(Solanaceae)等在内的24个双子叶家族和3个单子叶家族的100多种植物,是具有重要经济价值的植物病毒之一.为研究TAV BJ株系(Tomato aspermy virus,TAV-BJ)的基因组功能,本实验对TAV-BJ基因组克隆测序,并构建侵染性克隆.以TAV-BJ侵染心叶烟(ic otiana glutinosa)的总RNA为模板,RT-PCR获得其RNA2和RNA3;以TAV-BJ的dsRNA为模板,RT-PCR获得全长RNA1,目的片段PCR产物克隆测序获得TAV-BJ基因组全序列信息.RNA1全长3 409 nt,编码994个氨基酸的1a蛋白;RNA2全长3 023 nt,含2个开放阅读框(open reading frame,ORF),2a ORF编码829个氨基酸的2a蛋白,2b ORF编码78个氨基酸的2b蛋白;RNA3全长为2 216 nt,包含2个ORF,3a ORF编码247个氨基酸的3a蛋白,外壳蛋白(coat protein,CP)ORF 编码219个氨基酸的CP蛋白(TAV-BJ基因组RNA1、2和3 GenBank登录号分别为HQ424163,HQ424164和HQ424165).TAV-BJ基因组cDNA克隆体外转录成RNA并接种于心叶烟上,结果表明转录产物在寄主上的症状反应和TAV-BJ病毒粒子RNA的接种相一致,TAV-BJ基因组cDNA侵染性克隆具有活性.由TAV-BJ各个基因片段与缺失2b基因的黄瓜花叶病毒Fny株系(Cucumber mosaic virus,CMV-Fny△2b)构建的假重组病毒接种于心叶烟,结果显示TAV-BJ的RNA2和RNA3能恢复CMV-Fny△2b在寄主上症状反应.嵌合型RNA3F3aTcp和RNA3T3aFcp的症状反应结果表明,F1F2△2bRNA3 T3aFcp在寄主上产生花叶症状与F1 F2△2bT3相一致.本研究获得TAV-BJ的基因组序列,成功构建侵染性克隆,同时发现TAV-BJ的3a基因具有CMV-Fny的2b基因的某些功能.     

IBD和ND混合感染伴发大肠杆菌病的诊断

以流行病学、临床症状、病理变化和实验室诊断等方法确诊了１９９０年６～９月在河南省某肉鸡场暴发的鸡传染病为鸡新城疫（ＮＤ）和鸡传染性法氏囊病（ＩＢＤ）混合感染，并伴发了大肠杆菌病。本文还就发病的原因及其对策进行了讨论     

抗IBD高免卵黄抗体的研制

应用ＩＢＤ二价弱毒细胞苗和二价油乳剂灭活苗对鸡进行加强免疫，待高免鸡血清ＩＢＤＡＧＰ抗体效价达１：２５６以上时，收集高免蛋，用于制备抗ＩＢＤ高免卵黄抗体，制出的高免卵黄抗体ＩＢＤＡＧＰ效价为１：６４～１：１２８，用这种高免卵黄抗体对万余只ＩＢＤ病鸡进行治疗，剂量为每只鸡肌注１ｍｌ，总有效率在９０％以上。由此可见，ＩＢＤ高免卵黄抗体具有特异性好、治愈率高、取材方便、制造简便和使用方便等优点，适用于基层推广使用。     

大豆花叶病毒侵染性克隆研究进展

大豆花叶病毒(soybean mosaic virus,SMV)是一种株系复杂且不断变化、并对大豆的产量和质量造成恶劣影响的病毒,其严重的致病性受到学者的普遍关注。大豆花叶病毒侵染性克隆技术是研究其致病机理的行之有效的手段。该技术通过病毒侵染获得侵染性cDNA克隆,进一步分析引起症状的相应基因在植株生长过程中的作用机制,由此为SMV相关领域的研究奠定理论基础。本文就大豆花叶病毒侵染性克隆的构建策略和影响因素,以及其应用状况作一综述,以期为大豆花叶病毒的防治提供新的借鉴和思路。