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汉坦病毒感染的新生态学方面:范式转变与预防挑战——综述

New ecological aspects of hantavirus infection: a change of a paradigm and a challenge of prevention--a review.

作者信息

Zeier Martin, Handermann Michaela, Bahr Udo, Rensch Baldur, Müller Sandra, Kehm Roland, Muranyi Walter, Darai Gholamreza

机构信息

Sektion Nephrologie, Klinikum der Universität Heidelberg, Bergheimerstr. 56a, D-69115, Heidelberg, Federal Republic of Germany.

出版信息

Virus Genes. 2005 Mar;30(2):157-80. doi: 10.1007/s11262-004-5625-2.

Abstract

In the last decades a significant number of so far unknown or underestimated pathogens have emerged as fundamental health hazards of the human population despite intensive research and exceptional efforts of modern medicine to embank and eradicate infectious diseases. Almost all incidents caused by such emerging pathogens could be ascribed to agents that are zoonotic or expanded their host range and crossed species barriers. Many different factors influence the status of a pathogen to remain unnoticed or evolves into a worldwide threat. The ability of an infectious agent to adapt to changing environmental conditions and variations in human behavior, population development, nutrition, education, social, and health status are relevant factors affecting the correlation between pathogen and host. Hantaviruses belong to the emerging pathogens having gained more and more attention in the last decades. These viruses are members of the family Bunyaviridae and are grouped into a separate genus known as Hantavirus. The serotypes Hantaan (HTN), Seoul (SEO), Puumala (PUU), and Dobrava (DOB) virus predominantly cause hemorrhagic fever with renal syndrome (HFRS), a disease characterized by renal failure, hemorrhages, and shock. In the recent past, many hantavirus isolates have been identified and classified in hitherto unaffected geographic regions in the New World (North, Middle, and South America) with characteristic features affecting the lungs of infected individuals and causing an acute pulmonary syndrome. Hantavirus outbreaks in the United States of America at the beginning of the 10th decade of the last century fundamentally changed our knowledge about the appearance of the hantavirus specific clinical picture, mortality, origin, and transmission route in human beings. The hantavirus pulmonary syndrome (HPS) was first recognized in 1993 in the Four Corners Region of the United States and had a lethality of more than 50%. Although the causative virus was first termed in connection with the geographic name of its outbreak region the analysis of the individual viruses indicate that the causing virus of HPS was a genetically distinct hantavirus and consequently termed as Sin Nombre virus. Hantaviruses are distributed worldwide and are assumed to share a long time period of co-evolution with specific rodent species as their natural reservoir. The degree of relatedness between virus serotypes normally coincides with the relatedness between their respective hosts. There are no known diseases that are associated with hantavirus infections in rodents underlining the amicable relationship between virus and host developed by mutual interaction in hundreds of thousands of years. Although rodents are the major reservoir, antibodies against hantaviruses are also present in domestic and wild animals like cats, dogs, pigs, cattle, and deer. Domestic animals and rodents live jointly in a similar habitat. Therefore the transmission of hantaviruses from rodents to domestic animals seems to be possible, if the target organs, tissues, and cell parenchyma of the co-habitat domestic animals possess adequate virus receptors and are suitable for hantavirus entry and replication. The most likely incidental infection of species other than rodents as for example humans turns hantaviruses from harmless to life-threatening pathogenic agents focusing the attention on this virus group, their ecology and evolution in order to prevent the human population from a serious health risk. Much more studies on the influence of non-natural hosts on the ecology of hantaviruses are needed to understand the directions that the hantavirus evolution could pursue. At least, domestic animals that share their environmental habitat with rodents and humans particularly in areas known as high endemic hantavirus regions have to be copiously screened. Each transfer of hantaviruses from their original natural hosts to other often incidental hosts is accompanied by a change of ecology, a change of environment, a modulation of numerous factors probably influencing the pathogenicity and virulence of the virus. The new environment exerts a modified evolutionary pressure on the virus forcing it to adapt and probably to adopt a form that is much more dangerous for other host species compared to the original one.

摘要

在过去几十年中,尽管现代医学进行了深入研究并付出了巨大努力来控制和根除传染病,但仍有大量此前未知或被低估的病原体成为人类的基本健康威胁。几乎所有由这些新出现的病原体引起的事件都可归因于具有人畜共患病性质或扩大了宿主范围并跨越物种屏障的病原体。许多不同因素影响着病原体未被注意或演变成全球威胁的状况。传染病原体适应不断变化的环境条件以及人类行为、人口发展、营养、教育、社会和健康状况变化的能力,是影响病原体与宿主之间关系的相关因素。汉坦病毒属于在过去几十年中越来越受到关注的新出现病原体。这些病毒是布尼亚病毒科的成员,被归为一个单独的属,即汉坦病毒属。汉滩(HTN)、汉城(SEO)、普马拉(PUU)和多布拉瓦(DOB)病毒血清型主要引起肾综合征出血热(HFRS),这是一种以肾衰竭、出血和休克为特征的疾病。最近,在新世界(北美洲、中美洲和南美洲)此前未受影响的地理区域中发现并分类了许多汉坦病毒分离株,这些分离株具有影响受感染个体肺部并导致急性肺综合征的特征。上世纪90年代初美国的汉坦病毒疫情从根本上改变了我们对汉坦病毒特定临床表现、死亡率、起源和人类传播途径的认识。汉坦病毒肺综合征(HPS)于1993年首次在美国四角地区被确认,致死率超过50%。尽管致病病毒最初是根据其爆发地区的地理名称来命名的,但对各个病毒的分析表明,HPS的致病病毒是一种基因上不同的汉坦病毒,因此被称为辛诺柏病毒。汉坦病毒分布于全球,据推测与特定啮齿动物物种作为其自然宿主共同进化了很长时间。病毒血清型之间的亲缘关系程度通常与它们各自宿主之间的亲缘关系一致。目前尚无已知与啮齿动物汉坦病毒感染相关的疾病,这突出了病毒与宿主在数十万年的相互作用中形成的友好关系。尽管啮齿动物是主要宿主,但在家养动物和野生动物如猫、狗、猪、牛和鹿中也存在抗汉坦病毒抗体。家养动物和啮齿动物共同生活在相似的栖息地。因此,如果共同生活的家养动物的靶器官、组织和细胞实质具有足够的病毒受体且适合汉坦病毒进入和复制,那么汉坦病毒从啮齿动物传播到家养动物似乎是可能的。除啮齿动物外的其他物种(如人类)最有可能的偶然感染使汉坦病毒从无害病原体转变为危及生命的病原体,这使得人们将注意力集中在这个病毒群体及其生态学和进化上,以防止人类面临严重的健康风险。需要更多关于非天然宿主对汉坦病毒生态学影响的研究,以了解汉坦病毒进化可能遵循的方向。至少,在与啮齿动物和人类共享环境栖息地的家养动物中,特别是在已知汉坦病毒高流行地区,必须进行大量筛查。汉坦病毒从其原始天然宿主向其他通常为偶然宿主的每次转移都伴随着生态变化、环境变化以及可能影响病毒致病性和毒力的众多因素的调节。新环境对病毒施加了改变的进化压力,迫使它适应并可能采用一种与原始形式相比对其他宿主物种更危险的形式。

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