贵州省四种蝙蝠携带病毒组

翼手目(Chiroptera)动物已被确认是人畜共患病毒的重要自然宿主。贵州省翼手目物种多样性资源丰富,包括了2亚目7科19属65种,但在其携带病毒方面的研究仍然不全面。本文基于病毒宏基因组学和s RNA病毒检测,对贵州省广泛分布的大蹄蝠(Hipposideriderosarmiger)、三叶蹄蝠(Aselliscus wheeleri)、贵州菊头蝠(Rhinolophus rex)和皮氏菊头蝠(R. pearsoni)携带的病毒进行注释及鉴定。通过分析得到所携带病毒的种类;并比较了贵州省与云南省和广西省3个地区翼手目携带病毒在种类上的差异。结果显示,在4种蝙蝠中检测出脊椎动物病毒、昆虫病毒、植物病毒、细菌病毒4大类,共计53科111属170余种病毒,其中具有公共卫生学意义病毒9科10属46种,如:人疱疹病毒1型病毒(Human herpesvirus 1)、戊型肝炎病毒(Hepatitis E virus)、人乳头瘤病毒16型(Human papillomavirustype16)等相关的病毒。贵州省与云南省和广西省3个地区的蝙蝠所携带病毒种类比较发现,只有腺病毒科(Adenovir...     

Viral discovery and sequence recovery using DNA microarrays

Because of the constant threat posed by emerging infectious diseases and the limitations of existing approaches used to identify new pathogens, there is a great demand for new technological methods for viral discovery. We describe herein a DNA microarray-based platform for novel virus identification and characterization. Central to this approach was a DNA microarray designed to detect a wide range of known viruses as well as novel members of existing viral families; this microarray contained the most highly conserved 70mer sequences from every fully sequenced reference viral genome in GenBank. During an outbreak of severe acute respiratory syndrome (SARS) in March 2003, hybridization to this microarray revealed the presence of a previously uncharacterized coronavirus in a viral isolate cultivated from a SARS patient. To further characterize this new virus, approximately 1 kb of the unknown virus genome was cloned by physically recovering viral sequences hybridized to individual array elements. Sequencing of these fragments confirmed that the virus was indeed a new member of the coronavirus family. This combination of array hybridization followed by direct viral sequence recovery should prove to be a general strategy for the rapid identification and characterization of novel viruses and emerging infectious disease.     

Evolutionary insights into the ecology of coronaviruses

Although many novel members of the Coronaviridae have recently been recognized in different species, the ecology of coronaviruses has not been established. Our study indicates that bats harbor a much wider diversity of coronaviruses than any other animal species. Dating of different coronavirus lineages suggests that bat coronaviruses are older than those recognized in other animals and that the human severe acute respiratory syndrome (SARS) coronavirus was directly derived from viruses from wild animals in wet markets of southern China. Furthermore, the most closely related bat and SARS coronaviruses diverged in 1986, an estimated divergence time of 17 years prior to the outbreak, suggesting that there may have been transmission via an unknown intermediate host. Analysis of lineage-specific selection pressure also indicated that only SARS coronaviruses in civets and humans were under significant positive selection, also demonstrating a recent interspecies transmission. Analysis of population dynamics revealed that coronavirus populations in bats have constant population growth, while viruses from all other hosts show epidemic-like increases in population. These results indicate that diverse coronaviruses are endemic in different bat species, with repeated introductions to other animals and occasional establishment in other species. Our findings suggest that bats are likely the natural hosts for all presently known coronavirus lineages and that all coronaviruses recognized in other species were derived from viruses residing in bats. Further surveillance of bat and other animal populations is needed to fully describe the ecology and evolution of this virus family.     

Bats and Viruses： a Brief Review

Bats, probably the most abundant, diverse and geographically dispersed vertebrates on earth, have recently been shown to be the reservoir hosts of a number of emerging viruses responsible for severe human and livestock disease outbreaks. Flying foxes have been demonstrated to be the natural reservoir for Hendra and Nipah viruses. Evidence supporting the possibility of bats as potential reservoirs for SARS coronavirus (SARS-CoV) and Ebola virus has also been reported. The recent discovery of these viruses and other viruses occurring naturally in the bat population provides a unique insight into a diverse pool of potentially emergent and pathogenic viruses. The factors which influence the ability of zoonotic viruses to effectively cross the species barrier from bats to other animal populations are poorly understood. A brief review is provided here on the recently emerged bat viruses and on current and future strategies for research in this area.     

Deciphering the bat virome catalog to better understand the ecological diversity of bat viruses and the bat origin of emerging infectious diseases

Studies have demonstrated that ~60%–80% of emerging infectious diseases (EIDs) in humans originated from wild life. Bats are natural reservoirs of a large variety of viruses, including many important zoonotic viruses that cause severe diseases in humans and domestic animals. However, the understanding of the viral population and the ecological diversity residing in bat populations is unclear, which complicates the determination of the origins of certain EIDs. Here, using bats as a typical wildlife reservoir model, virome analysis was conducted based on pharyngeal and anal swab samples of 4440 bat individuals of 40 major bat species throughout China. The purpose of this study was to survey the ecological and biological diversities of viruses residing in these bat species, to investigate the presence of potential bat-borne zoonotic viruses and to evaluate the impacts of these viruses on public health. The data obtained in this study revealed an overview of the viral community present in these bat samples. Many novel bat viruses were reported for the first time and some bat viruses closely related to known human or animal pathogens were identified. This genetic evidence provides new clues in the search for the origin or evolution pattern of certain viruses, such as coronaviruses and noroviruses. These data offer meaningful ecological information for predicting and tracing wildlife-originated EIDs.     

Human activities link fruit bat presence to Ebola virus disease outbreaks

1. A significant link between forest loss and fragmentation and outbreaks of Ebola virus disease (EVD) in humans has been documented. Deforestation may alter the natural circulation of viruses and change the composition, abundance, behaviour and possibly viral exposure of reservoir species. This in turn might increase contact between infected animals and humans.
2. Fruit bats of the family Pteropodidae have been suspected as reservoirs of the Ebola virus. At present, the only evidence associating fruit bats with EVD is the presence of seropositive individuals in eight species and polymerase chain reaction-positive individuals in three of these.
3. Our study investigates whether human activities can increase African fruit bat geographical ranges and whether this influence overlaps geographically with EVD outbreaks that, in turn, are favoured by deforestation.
4. We use species observation records for the 20 fruit bat species found in favourable areas for the Ebola virus to determine factors affecting the bats' range inside the predicted Ebola virus area. We do this by employing a hypothetico-deductive approach based on favourability modelling.
5. We show that the range of some fruit bat species is linked to human activities within the favourable areas for the Ebola virus. More specifically, the areas where human activities favour the presence of five fruit bat species overlap with the areas where EVD outbreaks in humans were themselves favoured by deforestation. These five species are as follows: Eidolon helvum, Epomops franqueti, Megaloglossus woermanni, Micropteropus pusillus and Rousettus aegyptiacus. Of these five, all but Megaloglossus woermanni have recorded seropositive individuals. For the remaining 15 bat species, we found no biogeographical support for the hypothesis that positive human influence on fruit bats could be associated with EVD outbreaks in deforested areas within the tropical forest biome in West and Central Africa.
6. Our work is a useful first step allowing further investigation of the networks and pathways that may lead to an EVD outbreak. The modelling framework we employ here can be used for other emerging infectious diseases.

     

Adaptive modeling of viral diseases in bats with a focus on rabies

Many emerging and reemerging viruses, such as rabies, SARS, Marburg, and Ebola have bat populations as disease reservoirs. Understanding the spillover from bats to humans and other animals, and the associated health risks requires an analysis of the disease dynamics in bat populations. Traditional compartmental epizootic models, which are relatively easy to implement and analyze, usually impose unrealistic aggregation assumptions about disease-related structure and depend on parameters that frequently are not measurable in field conditions. We propose a novel combination of computational and adaptive modeling approaches that address the maintenance of emerging diseases in bat colonies through individual (intra-host) models of the response of the host to a viral challenge. The dynamics of the individual models are used to define survival, susceptibility and transmission conditions relevant to epizootics as well as to develop and parametrize models of the disease evolution into uniform and diverse populations. Applications of the proposed approach to modeling the effects of immunological heterogeneity on the dynamics of bat rabies are presented.     

Feature Selection Methods for Identifying Genetic Determinants of Host Species in RNA Viruses

Despite environmental, social and ecological dependencies, emergence of zoonotic viruses in human populations is clearly also affected by genetic factors which determine cross-species transmission potential. RNA viruses pose an interesting case study given their mutation rates are orders of magnitude higher than any other pathogen – as reflected by the recent emergence of SARS and Influenza for example. Here, we show how feature selection techniques can be used to reliably classify viral sequences by host species, and to identify the crucial minority of host-specific sites in pathogen genomic data. The variability in alleles at those sites can be translated into prediction probabilities that a particular pathogen isolate is adapted to a given host. We illustrate the power of these methods by: 1) identifying the sites explaining SARS coronavirus differences between human, bat and palm civet samples; 2) showing how cross species jumps of rabies virus among bat populations can be readily identified; and 3) de novo identification of likely functional influenza host discriminant markers.     

新型人冠状病毒HCoV—NL63和HCoV-HKU1的研究进展

多年来,人们公认的人冠状病毒包括HCoV-229E和HCoV-0C43等2株。但2002-2003年,由一种新型人冠状病毒SARS-CoV所引发的全球范围的严重急性呼吸综合征（SARS）的流行,使多国蒙受巨大损失,由此,冠状病毒又成为研究的焦点。随着分子生物学技术的发展,2004-2005年,又发现了2种新型人冠状病毒HCoV-NL63和HCoV-HKU1。在此,就这2种病毒的发现、流行情况,及其与疾病的相关性做一简要综述。     

Duration of Maternal Antibodies against Canine Distemper Virus and Hendra Virus in Pteropid Bats

Old World frugivorous bats have been identified as natural hosts for emerging zoonotic viruses of significant public health concern, including henipaviruses (Nipah and Hendra virus), Ebola virus, and Marburg virus. Epidemiological studies of these viruses in bats often utilize serology to describe viral dynamics, with particular attention paid to juveniles, whose birth increases the overall susceptibility of the population to a viral outbreak once maternal immunity wanes. However, little is understood about bat immunology, including the duration of maternal antibodies in neonates. Understanding duration of maternally derived immunity is critical for characterizing viral dynamics in bat populations, which may help assess the risk of spillover to humans. We conducted two separate studies of pregnant Pteropus bat species and their offspring to measure the half-life and duration of antibodies to 1) canine distemper virus antigen in vaccinated captive Pteropus hypomelanus; and 2) Hendra virus in wild-caught, naturally infected Pteropus alecto. Both of these pteropid bat species are known reservoirs for henipaviruses. We found that in both species, antibodies were transferred from dam to pup. In P. hypomelanus pups, titers against CDV waned over a mean period of 228.6 days (95% CI: 185.4–271.8) and had a mean terminal phase half-life of 96.0 days (CI 95%: 30.7–299.7). In P. alecto pups, antibodies waned over 255.13 days (95% CI: 221.0–289.3) and had a mean terminal phase half-life of 52.24 days (CI 95%: 33.76–80.83). Each species showed a duration of transferred maternal immunity of between 7.5 and 8.5 months, which was longer than has been previously estimated. These data will allow for more accurate interpretation of age-related Henipavirus serological data collected from wild pteropid bats.     

A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special?

Bats are the natural reservoirs of a number of high-impact viral zoonoses. We present a quantitative analysis to address the hypothesis that bats are unique in their propensity to host zoonotic viruses based on a comparison with rodents, another important host order. We found that bats indeed host more zoonotic viruses per species than rodents, and we identified life-history and ecological factors that promote zoonotic viral richness. More zoonotic viruses are hosted by species whose distributions overlap with a greater number of other species in the same taxonomic order (sympatry). Specifically in bats, there was evidence for increased zoonotic viral richness in species with smaller litters (one young), greater longevity and more litters per year. Furthermore, our results point to a new hypothesis to explain in part why bats host more zoonotic viruses per species: the stronger effect of sympatry in bats and more viruses shared between bat species suggests that interspecific transmission is more prevalent among bats than among rodents. Although bats host more zoonotic viruses per species, the total number of zoonotic viruses identified in bats (61) was lower than in rodents (68), a result of there being approximately twice the number of rodent species as bat species. Therefore, rodents should still be a serious concern as reservoirs of emerging viruses. These findings shed light on disease emergence and perpetuation mechanisms and may help lead to a predictive framework for identifying future emerging infectious virus reservoirs.     

抵御新发、突发病毒性传染病的新思路——天然免疫机制的系统医学研究和针对宿主的广谱抗病毒药物的研发

病毒性传染疾病是人类社会的重大威胁,严重危害人民生命安全和国家、社会安定.随着国内外经济发展,城镇化、都市化、全球化的进程加快,新发和突发病毒性传染病呈现不断增高的趋势,如艾滋病病毒、严重急性呼吸综合征病毒、禽流感病毒、甲流感病毒、埃博拉病毒等近年来一次又一次在世界不同地区频繁发生并蔓延、流行.本次埃博拉病毒在西非的爆发和疫情失控更再次警示我国和国际社会关于发展有效防治新发、突发病毒性传染病措施的重要性和紧迫性.天然免疫与宿主抗病研究领域的突破性进展为解决该世界性难题开辟了新的思路和途径.     

Cell entry mechanism of coronaviruses: implication in their pathogenesis

Coronaviruses infect many species of animals, including humans. Among them, murine coronavirus, mouse hepatitis virus (MHV) has been well studied as a model of human diseases, such as hepatitis and demyelinating disease. An agent causing severe acute respiratory disease (SARS), SARS coronavirus (SARS-CoV), is a newcomer in this genus, however, it is now one of the most studied coronaviruses due to its medical impact. The receptors of those two viruses have been identified and their cell entry mechanism has been actively investigated. Recently, SARS-CoV cell entry mechanism is shown to be different from that of other enveloped viruses, including MHV. In this review, cell entry mechanism of those two viruses is described, stressing on the difference and similarity found between those two viruses.     

Network analysis of host–virus communities in bats and rodents reveals determinants of cross‐species transmission

Bats are natural reservoirs of several important emerging viruses. Cross‐species transmission appears to be quite common among bats, which may contribute to their unique reservoir potential. Therefore, understanding the importance of bats as reservoirs requires examining them in a community context rather than concentrating on individual species. Here, we use a network approach to identify ecological and biological correlates of cross‐species virus transmission in bats and rodents, another important host group. We show that given our current knowledge the bat viral sharing network is more connected than the rodent network, suggesting viruses may pass more easily between bat species. We identify host traits associated with important reservoir species: gregarious bats are more likely to share more viruses and bats which migrate regionally are important for spreading viruses through the network. We identify multiple communities of viral sharing within bats and rodents and highlight potential species traits that can help guide studies of novel pathogen emergence.     

Pathogenicity and transmissibility of 2019-nCoV—A quick overview and comparison with other emerging viruses

A zoonotic coronavirus, tentatively labeled as 2019-nCoV by the World Health Organization (WHO), has been identified as the causative agent of the viral pneumonia outbreak in Wuhan, China, at the end of 2019. Although 2019-nCoV can cause a severe respiratory illness like SARS and MERS, evidence from clinics suggested that 2019-nCoV is generally less pathogenic than SARS-CoV, and much less than MERS-CoV. The transmissibility of 2019-nCoV is still debated and needs to be further assessed. To avoid the 2019-nCoV outbreak turning into an epidemic or even a pandemic and to minimize the mortality rate, China activated emergency response procedures, but much remains to be learned about the features of the virus to refine the risk assessment and response. Here, the current knowledge in 2019-nCoV pathogenicity and transmissibility is summarized in comparison with several commonly known emerging viruses, and information urgently needed for a better control of the disease is highlighted.     

Viral evolution and the emergence of SARS coronavirus

The recent appearance of severe acute respiratory syndrome coronavirus (SARS-CoV) highlights the continual threat to human health posed by emerging viruses. However, the central processes in the evolution of emerging viruses are unclear, particularly the selection pressures faced by viruses in new host species. We outline some of the key evolutionary genetic aspects of viral emergence. We emphasize that, although the high mutation rates of RNA viruses provide them with great adaptability and explain why they are the main cause of emerging diseases, their limited genome size means that they are also subject to major evolutionary constraints. Understanding the mechanistic basis of these constraints, particularly the roles played by epistasis and pleiotropy, is likely to be central in explaining why some RNA viruses are more able than others to cross species boundaries. Viral genetic factors have also been implicated in the emergence of SARS-CoV, with the suggestion that this virus is a recombinant between mammalian and avian coronaviruses. We show, however, that the phylogenetic patterns cited as evidence for recombination are more probably caused by a variation in substitution rate among lineages and that recombination is unlikely to explain the appearance of SARS in humans.     

Detection of diverse viruses in alimentary specimens of bats in Macau

Bats carry a variety of viruses, and some of them cause public health problems. Macau, which is famous for its gambling industry, has a complex population structure. The globalization in such an international metropolis has enhanced the chance of disease transmission. Therefore, surveillance of zoonotic viruses is necessary for the early warning of potential emerging infectious diseases. Here, we report the first surveillance of bat viruses in Macau. In this study, we collected 1004 samples involving 10 bat species from 7 sites from April 2015 to May 2016, and examined the presence of viruses using nucleic acid-based methods. Coronaviruses, adenoviruses and paramyxoviruses were detected in these samples, with a high prevalence of coronaviruses. While, none was positive for hepatitis A virus, hepatitis E virus or hantavirus. Co-infections are not common in those bat species, but coronavirus HKU6 and adenovirus can be found commonly occurred in Myotis ricketti.

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浅议野生动物与人类共患疾病

可能以野生动物为病源的SARS的爆发和流行,使得人们更加关注野生动物传染性疾病对人类健康的威胁。特别是近30年来新出现的多种传染病,自然宿主几乎都是野生动物。本文就野生动物与人类的共患疾病做了简单的历史回顾。新的野生动物传染病的出现提示：如何避免和应对类似事件的再度发生或减少发生的频次、如何处理人与野生动物之间的关系等问题迫在眉睫,而解决这些问题的根本在于人类应该认识自身的位置,尊重自然和其它生命,采取各种有效的措施,保障人类与野生动物安全接触。只有保证生态系统和生物多样性的健康,才能真正维护人类自身的健康。     

The experience of the 2003 SARS outbreak as a traumatic stress among frontline healthcare workers in Toronto: lessons learned

The outbreak of severe acute respiratory syndrome (SARS) in the first half of 2003 in Canada was unprecedented in several respects. Understanding the psychological impact of the outbreak on healthcare workers, especially those in hospitals, is important in planning for future outbreaks of emerging infectious diseases. This review draws upon qualitative and quantitative studies of the SARS outbreak in Toronto to outline the factors that contributed to healthcare workers' experiencing the outbreak as a psychological trauma. Overall, it is estimated that a high degree of distress was experienced by 29-35% of hospital workers. Three categories of contributory factors were identified. Relevant contextual factors were being a nurse, having contact with SARS patients and having children. Contributing attitudinal factors and processes were experiencing job stress, perceiving stigmatization, coping by avoiding crowds and colleagues, and feeling scrutinized. Pre-existing trait factors also contributed to vulnerability. Lessons learned from the outbreak include: (i) that effort is required to mitigate the psychological impact of infection control procedures, especially the interpersonal isolation that these procedures promote; (ii) that effective risk communication is a priority early in an outbreak; (iii) that healthcare workers may have a role in influencing patterns of media coverage that increase or decrease morale; (iv) that healthcare workers benefit from resources that facilitate reflection on the effects of extraordinary stressors; and (v) that healthcare workers benefit from practical interventions that demonstrate tangible support from institutions.     

Impact of quarantine on the 2003 SARS outbreak: a retrospective modeling study

During the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak, traditional intervention measures such as quarantine and border control were found to be useful in containing the outbreak. We used laboratory verified SARS case data and the detailed quarantine data in Taiwan, where over 150,000 people were quarantined during the 2003 outbreak, to formulate a mathematical model which incorporates Level A quarantine (of potentially exposed contacts of suspected SARS patients) and Level B quarantine (of travelers arriving at borders from SARS affected areas) implemented in Taiwan during the outbreak. We obtain the average case fatality ratio and the daily quarantine rate for the Taiwan outbreak. Model simulations is utilized to show that Level A quarantine prevented approximately 461 additional SARS cases and 62 additional deaths, while the effect of Level B quarantine was comparatively minor, yielding only around 5% reduction of cases and deaths. The combined impact of the two levels of quarantine had reduced the case number and deaths by almost a half. The results demonstrate how modeling can be useful in qualitative evaluation of the impact of traditional intervention measures for newly emerging infectious diseases outbreak when there is inadequate information on the characteristics and clinical features of the new disease-measures which could become particularly important with the looming threat of global flu pandemic possibly caused by a novel mutating flu strain, including that of avian variety.