Theiler?s virus as a potential cause of Vilyuisk encephalitis

泰勒病毒是 Vilyuisk 脑炎的潜在病因

• 批准号: 7872770
• 负责人: HOWARD Lee LIPTON
• 金额: $ 19.43万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7872770
• 关键词: Abbreviations; Acute; Adult; Air; Amoeba genus; Arboviruses; Area; Biological; Blood; Brain; Brazil; Canada; Capital; Cardiovirus; Central Nervous System Diseases; Central Nervous System Infections; Cerebrospinal Fluid; Child; Chronic; Clinical; Collaborations; Complementary DNA; Disease; Distant; Encephalitis; Encephalitis Viruses; Encephalomyelitis; Enzyme-Linked Immunosorbent Assay; Europe; Event; Experimental Animal Model; Family; Feces; Fever; Freedom; Genome; Geographic Locations; Germany; Goals; Human; Human Virus; Immune Sera; Individual; Institutes; Investigation; Knowledge; Learning; Link; Mengovirus; Meningeal; Meningitis; Moscow; Multiple Sclerosis; Mus; Names; Nature; Netherlands; Neuraxis; Nigeria; North America; Oligoclonal Bands; Oligonucleotide Microarrays; Oligonucleotides; Pakistan; Personal Communication; Phylogenetic Analysis; Poliomyelitis; Property; RNA; Rattus; Research Personnel; Rivers; Russia; Sampling; Serological; Serum; Siberia; Specimen; Structure; TMEV; Testing; Theilovirus; Time; Travel; United States; Upper respiratory tract; Vertebrate Viruses; Viral; Viral Encephalitis; Virus; case control; catalyst; cross reactivity; disability; disease classification; gastrointestinal; interest; nervous system disorder; neutralizing antibody; public health relevance; research study; respiratory

DESCRIPTION (provided by applicant): The goal of this R21 exploratory proposal is to determine whether the V-1 isolate, termed Vilyuisk human encephalitis virus (VHEV), which may represent a separate clade of theilovirus, is the causative agent of Vilyuisk encephalomyelitis (VE). Although the viral cause of VE remains unknown compelling evidence links VHEV to VE. VE has spread 400 km from the area of endemicity along the middle reaches of the Vilyui River to a new more populous geographic area in the Lena-Aldan river valleys where Yakutsk, the capital of the Sahka Republic in Siberia (Russia), is located. Globalization due to increased freedom of air travel could result in further spread of VE to other regions of the world. Recent identification of theiloviruses designated Saffold viruses (SafV) in children with respiratory and diarrheal diseases from separate geographic locations in North America and four other continents indicate that theiloviruses are global in distribution and commonly infect children and possibly adults. The emergence of theiloviruses is the catalyst for our renewed interest in the cause of VE since it is creditable that theiloviruses cause human central nervous system (CNS) diseases. In fact, the PI has just learned of SafV isolations from cases of encephalitis in children in Europe. Therefore, it is intriguing to speculate theiloviruses represent an emerging group of human viruses that cause central nervous system CNS infections, including VE (hypothesis). Two specific aims are proposed: (1) To investigate a link between VHEV and the clinical disease of VE, we will determine serum titers and serum:CSF ratios of ELISA and neutralizing antibodies to VHEV in VE cases and controls, VE cerebrospinal fluid (CSF) oligoclonal band (OCB) reactivity to VHEV, and whether a 320- bp Cardiovirus amplicon that includes the highly variable VP2 puff (EF) structures can be amplified from total RNA extracted from VE CSF. (2) In the event that VHEV cannot be linked to VE, reverse transcribed cDNA from total RNA extracted from VE CSF will be hybridized to oligonucleotide viral microarrays (GreenChipsPm) and also used for high-throughput sequencing to detect foreign (non-human) sequences of a specific vertebrate virus family by subtraction of the human transcriptisome. PUBLIC HEALTH RELEVANCE: This is an exploratory proposal to determine the viral cause of a chronic central nervous system disease that occurs in the Sahka Republic in far northeastern Russia (Siberia). This disease, Vilyuisk encephalomyelitis, has some similarities to multiple sclerosis and appears to be caused by a human Theilovirus. The murine counterpart, Theiler's murine encephalomyelitis virus, provides a highly relevant experimental animal model for multiple sclerosis.

描述（由申请人提供）：本R21探索性提案的目标是确定V-1分离物，称为维留斯克人脑炎病毒（VHEV），可能代表其病毒的一个单独分支，是否是维留斯克脑脊髓炎（VE）的病原体。尽管VE的病毒病因尚不清楚，但令人信服的证据将VHEV与VE联系起来。从流行区沿维柳伊河中游蔓延400公里，到西伯利亚（俄罗斯）萨卡共和国首都雅库茨克所在的列纳-阿尔丹河谷人口较多的新地理区域。由于航空旅行自由的增加，全球化可能导致VE进一步传播到世界其他地区。最近在北美和其他四大洲不同地理位置的患有呼吸道和腹泻疾病的儿童中发现了被称为藏红花病毒（SafV）的它们的伊洛病毒，这表明它们的伊洛病毒在全球分布，通常感染儿童，也可能感染成人。它们的伊洛病毒的出现是我们重新关注VE病因的催化剂，因为它们的伊洛病毒引起人类中枢神经系统（CNS）疾病是可信的。事实上，PI刚刚从欧洲儿童脑炎病例中了解到SafV的分离。因此，推测它们的伊洛病毒代表了一组新兴的人类病毒，引起中枢神经系统感染，包括VE（假设）。我们提出了两个具体目标：(1)为了研究VHEV与VE临床疾病之间的联系，我们将测定VE病例和对照组中VHEV的ELISA和中和抗体的血清滴度和血清：CSF比率，VE脑脊液（CSF）寡克隆带（OCB）对VHEV的反应性，以及是否可以从VE CSF中提取的总RNA中扩增出包含高度可变VP2 puff （EF）结构的320- bp的心脏病毒扩增子。(2)在VHEV不能与VE关联的情况下，从VE CSF中提取的总RNA中逆转录的cDNA将被杂交到寡核苷酸病毒微阵列（GreenChipsPm）上，并用于高通量测序，通过减除人类转录体来检测特定脊椎动物病毒家族的外源（非人类）序列。公共卫生相关性：这是一项探索性建议，旨在确定俄罗斯东北部（西伯利亚）萨卡共和国发生的一种慢性中枢神经系统疾病的病毒病因。这种疾病，维留斯克脑脊髓炎，与多发性硬化症有一些相似之处，似乎是由人类theilvirus引起的。小鼠的对应物，Theiler的小鼠脑脊髓炎病毒，为多发性硬化症提供了高度相关的实验动物模型。