A Review of Simulation Modelling Approaches Used for the Spread of Zoonotic Influenza Viruses in Animal and Human Populations

Increasing incidences of emerging and re‐emerging diseases that are mostly zoonotic (e.g. severe acute respiratory syndrome, avian influenza H5N1, pandemic influenza) has led to the need for a multidisciplinary approach to tackling these threats to public and animal health. Accordingly, a global movement of ‘One‐Health/One‐Medicine’ has been launched to foster collaborative efforts amongst animal and human health officials and researchers to address these problems. Historical evidence points to the fact that pandemics caused by influenza A viruses remain a major zoonotic threat to mankind. Recently, a range of mathematical and computer simulation modelling methods and tools have increasingly been applied to improve our understanding of disease transmission dynamics, contingency planning and to support policy decisions on disease outbreak management. This review provides an overview of methods, approaches and software used for modelling the spread of zoonotic influenza viruses in animals and humans, particularly those related to the animal‐human interface. Modelling parameters used in these studies are summarized to provide references for future work. This review highlights the limited application of modelling research to influenza in animals and at the animal‐human interface, in marked contrast to the large volume of its research in human populations. Although swine are widely recognized as a potential host for generating novel influenza viruses, and that some of these viruses, including pandemic influenza A/H1N1 2009, have been shown to be readily transmissible between humans and swine, only one study was found related to the modelling of influenza spread at the swine‐human interface. Significant gaps in the knowledge of frequency of novel viral strains evolution in pigs, farm‐level natural history of influenza infection, incidences of influenza transmission between farms and between swine and humans are clearly evident. Therefore, there is a need to direct additional research to the study of influenza transmission dynamics in animals and at the animal‐human interface.     

反刍动物瘤胃噬菌体的宏基因组学研究方法及进展

病毒(virus)存在于各种动物胃肠道中,反刍动物瘤胃也不例外.瘤胃是一个复杂且多样的微生态系统,包括细菌、真菌、原虫、古生菌和病毒等多种微生物.目前,多组学技术和生物信息学分析手段被广泛用于瘤胃细菌群落的研究.有研究表明,饲粮、环境及宿主基因型会对瘤胃细菌多样性和菌群结构产生影响;瘤胃细菌也会反过来影响宿主机体代谢、...     

New emerging viral zoonoses

New developments in the field of viral transmission from animal to man can be divided into four areas of study. First are the new viral zoonoses such as diseases caused by rotaviruses, Lassa virus and the animal orthopox viruses which will be more prevalent after the cessation of mandatory vaccination against smallpox. Secondly are the numerous ubiquitous viruses, such as adeno and herpesviruses, which in healthy animals lead only to clinically inapparent infections. A typical example of the third area is the recombination and hybridisation between animal and human influenza type A viruses. The final area is concerned with the transmission of viral zoonoses to man through food of animal origin.     

Animal noroviruses

Among enteric caliciviruses, noroviruses belong to the genus Norovirus, one of the four accepted genera in the family Caliciviridae. These single-stranded, positive-sense RNA viruses are highly variable both genetically and antigenically. Several animal enteric caliciviruses that are morphologically indistinguishable and genetically closely related to human noroviruses have been identified. The first bovine enteric noroviruses were described in Great Britain and are known as Newbury Agent 2. At least three genetic clusters of porcine noroviruses join together within genogroup II noroviruses. Human noroviruses are the most important cause of acute gastroenteritis illness in people of all ages. In the USA, they are associated with approximately 30-50% of all food-borne outbreaks. Until now, noroviruses have not been associated with gastroenteritis outbreaks in immunocompetent animals. Neither bovine nor porcine noroviruses can replicate in cell culture, although human norovirus can grow in a complex 3D culture system. However, the recently discovered murine noroviruses can replicate in cell culture and are therefore used as model viruses to study human noroviruses. This review focusses on virus classification, virion structure, pathogenesis, epidemiology, immune response and diagnosis of animal noroviruses in comparison with human noroviruses. The classification of animal enteric caliciviruses within the Norovirus genus raises the question of whether transmission from an animal reservoir to humans could occur. Answering this question is important in determining the risk of cross-species infections affecting the epidemiology and evolution of these viruses and so complicating the control of human norovirus infections.     

Oncogenic viruses of domestic animals

The objective of this article is to review the relevant oncogenic viruses of small animals. Basic scientific principles that have been discovered by research into feline leukemia and other animal cancer viruses have enhanced our understanding of oncogenesis and have led to practical methods of cancer control and prophylaxis.     

Avian influenza viruses in wild birds: a moving target

The long-standing evolutionary and ecological relationships between wild birds and influenza A viruses has created a broad pool of viral genetic diversity and a reservoir of potentially transmissible viruses. An understanding of these relationships can help us identify and modify critical control points to reduce transmission of avian influenza viruses into animal and human populations.     

Humanized animal viruses with special reference to the primate adaptation of morbillivirus.

This review article discusses the evolution of human viruses with special reference to paramyxoviruses. This family of viruses causes epidemics representing the dissemination of infection from one acutely infected host to the next. Since there is no repository for human paramyxoviruses in animals or in the form of persistent infections in man, the history of epidemics afflicting human civilization is short, presumably not exceeding 4000-5000 years. Evolutionary relationships can be deduced for comparison of nucleotide sequences of genes or even complete genomes. The present paramyxovirus genus will probably in the future be divided into two separate genera. In the genus morbillivirus, two pairs of more closely related virus types can be distinguished: canine and phocid viruses, and rinder-pest and measles viruses, respectively. It is speculated that recombination events may have occurred in the evolution of the morbillivirus archetype.     

Comparative antiviral and proviral factors in semen and vaccines for preventing viral dissemination from the male reproductive tract and semen

Many animal and human viruses are disseminated via semen, but there is little information on how to measure and stimulate protective antiviral immunity in the male reproductive tract and semen. This information is important since successful vaccination through the stimulation of protective immune responses could be a mechanism to prevent viral contamination of semen and subsequent wide spread viral dissemination. Even control of the infection by shortening the duration of viral shedding and lowering the viral load in semen would lessen the chances of viral dissemination through this route. This review will highlight the current knowledge of immunity in the male reproductive tract and summarize 'antiviral' as well as 'proviral' factors in semen such as cytokines, cells, antibodies, antimicrobial peptides, enzymes, hormones and growth factors. These factors must provide a fine balance between 'immunosuppression' in semen needed to protect sperm viability and 'immunocompetency' to prevent pathogen contamination. The review will also suggest continuing challenges to researchers for preventing viral dissemination via semen and propose a large animal model for continued research in this important area.     

Prevention and Control of Rabies in an Age of Global Travel: A Review of Travel‐ and Trade‐Associated Rabies Events – United States, 1986–2012

Rabies prevention and control efforts have been successful in reducing or eliminating virus circulation regionally through vaccination of specific reservoir populations. A notable example of this success is the elimination of canine rabies virus variant from the United States and many other countries. However, increased international travel and trade can pose risks for rapid, long‐distance movements of ill or infected persons or animals. Such travel and trade can result in human exposures to rabies virus during travel or transit and could contribute to the re‐introduction of canine rabies variant or transmission of other viral variants among animal host populations. We present a review of travel‐ and trade‐associated rabies events that highlight international public health obligations and collaborative opportunities for rabies prevention and control in an age of global travel. Rabies is a fatal disease that warrants proactive coordination among international public health and travel industry partners (such as travel agents, tour companies and airlines) to protect human lives and to prevent the movement of viral variants among host populations.     

Mechanisms of viral emergence

A number of virologic and environmental factors are involved in the emergence and re-emergence of viral disease. Viruses do not conservatively occupy a single and permanent ecological niche. Rather, due to their intrinsic capacity for genetic change, and to the evolvability of fitness levels, viruses display a potential to parasitize alternative host species. Mutation, recombination and genome segment reassortment, and combination of these molecular events, produce complex and phenotypically diverse populations of viruses, which constitute the raw material on which selection acts. The majority of emerging viral diseases of humans have a zoonotic origin. Sociologic and ecologic factors produce diverse and changing environments in which viral subpopulations have ample opportunities to be selected from intrinsically heterogeneous viral populations, particularly in the case of RNA viruses. In this manner, new human, animal and plant viruses have emerged periodically and, from all evidence, will continue to emerge. This article reviews some of the mechanisms that have been identified in viral emergence, with a focus on the importance of genetic variation of viruses, and on the general concept of biological complexity.     

Baited vaccines: A strategy to mitigate rodent‐borne viral zoonoses in humans

Rodents serve as the natural reservoir and vector for a variety of pathogens, some of which are responsible for severe and life‐threatening disease in humans. Despite the significant impact in humans many of these viruses, including Old and New World hantaviruses as well as Arenaviruses, most have no specific vaccine or therapeutic to treat or prevent human infection. The recent success of wildlife vaccines to mitigate rabies in animal populations offers interesting insight into the use of similar strategies for other zoonotic agents of human disease. In this review, we discuss the notion of using baited vaccines as a means to interrupt the transmission of viral pathogens between rodent reservoirs and to susceptible human hosts.     

Recent data on the epidemiology and prophylaxis of human rabies in France

Rabies is an animal disease which is transmitted to man only by accident, most often through the bite (more rarely after scratches or licks of mucosa) of a rabid animal, domestic or wild. A good knowledge of the epizootiology of animal rabies is therefore necessary to establish, on solid grounds, the prophylaxis of human rabies. Inter-human transmission of rabies being an exceptional event which will be considered separately, the epidemiology of human rabies mainly studies the sources and circumstances of human exposure to rabid animals, which differ according to the epizootiology of animal rabies in a given country: either enzootic (or hyperenzootic) canine rabies, or enzootic selvatic rabies. It appears that the risk of human rabies is higher in the first situation for two reasons: (i) rabies viruses show an increased virulence due to numerous serial passages in dogs (viruses with short incubation period) and (ii) high frequency of dog-man contacts due to the high density of both populations.     

Up to new tricks - a review of cross-species transmission of influenza A viruses

Influenza is a highly contagious disease that has burdened both humans and animals since ancient times. In humans, the most dramatic consequences of influenza are associated with periodically occurring pandemics. Pandemics require the emergence of an antigenically novel virus to which the majority of the population lacks protective immunity. Historically, influenza A viruses from animals have contributed to the generation of human pandemic viruses and they may do so again in the future. It is, therefore, critical to understand the epidemiological and molecular mechanisms that allow influenza A viruses to cross species barriers. This review summarizes the current knowledge of influenza ecology, and the viral factors that are thought to determine influenza A virus species specificity.     

Parvovirus infection in domestic companion animals.

Parvovirus infects a wide variety of species. The rapid evolution, environmental resistance, high dose of viral shedding, and interspecies transmission have made some strains of parvovirus infection difficult to control within domestic animal populations. Some parvoviruses in companion animals, such as canine parvovirus (CPV) 1 and feline parvovirus, have demonstrated minimal evolution over time. In contrast, CPV 2 has shown wide adaptability with rapid evolution and frequent mutations. This article briefly discusses these three diseases, with emphasis on virus evolution and the challenges to protecting susceptible companion animal populations.     

Faecal virome of red foxes from peri-urban areas

Red foxes (Vulpes vulpes) are the most abundant carnivore species in the Northern Hemisphere. Since their populations are well established in peri-urban and urban areas, they represent a potential reservoir of viruses that transmit from wildlife to humans or domestic animals. In this study, we evaluated the faecal virome of juvenile and adult foxes from peri-urban areas in central Croatia. The dominating mammalian viruses were fox picobirnavirus and parvovirus. The highest number of viral reads (N = 1412) was attributed to a new fox circovirus and complete viral genome was de novo assembled from the high-throughput sequencing data. Fox circovirus is highly similar to dog circoviruses identified in diseased dogs in USA and Italy, and to a recently discovered circovirus of foxes with neurologic disease from the United Kingdom. Our fox picobirnavirus was more closely related to the porcine and human picobirnaviruses than to known fox picobirnaviruses.     

Recent developments in the epidemiology of virus diseases

There is continual variation in viral epidemics regarding clinical symptoms, duration and disappearance, and the emergence of new diseases. This can be observed in both human and animal diseases. This evolution of virus diseases is mainly related to three factors: aetiological agent, host and environment. As far as genetic alterations of the virus are concerned, two major mechanisms are involved: mutations such as recombination and reassortment; and selection for resistance or susceptibility. This review focuses on the epidemiology of newly emerged virus diseases in man and animals, such as acquired immunodeficiency syndrome, haemorraghic fevers, bovine spongiform encephalopathy, canine haemorraghic disease and respiratory syndrome in horses.     

Hepatitis E virus and related viruses in wild,domestic and zoo animals: A review

Hepatitis E is a human disease mainly characterized by acute liver illness, which is caused by infection with the hepatitis E virus (HEV). Large hepatitis E outbreaks have been described in developing countries; however, the disease is also increasingly recognized in industrialized countries. Mortality rates up to 25% have been described for pregnant women during outbreaks in developing countries. In addition, chronic disease courses could be observed in immunocompromised transplant patients. Whereas the HEV genotypes 1 and 2 are mainly confined to humans, genotypes 3 and 4 are also found in animals and can be zoonotically transmitted to humans. Domestic pig and wild boar represent the most important reservoirs for these genotypes. A distinct subtype of genotype 3 has been repeatedly detected in rabbits and a few human patients. Recently, HEV genotype 7 has been identified in dromedary camels and in an immunocompromised transplant patient. The reservoir animals get infected with HEV without showing any clinical symptoms. Besides these well‐known animal reservoirs, HEV‐specific antibodies and/or the genome of HEV or HEV‐related viruses have also been detected in many other animal species, including primates, other mammals and birds. In particular, genotypes 3 and 4 infections are documented in many domestic, wildlife and zoo animal species. In most cases, the presence of HEV in these animals can be explained by spillover infections, but a risk of virus transmission through contact with humans cannot be excluded. This review gives a general overview on the transmission pathways of HEV to humans. It particularly focuses on reported serological and molecular evidence of infections in wild, domestic and zoo animals with HEV or HEV‐related viruses. The role of these animals for transmission of HEV to humans and other animals is discussed.     

Viruses of waterfowl

Viral disease can cause substantial mortality in wild populations of ducks as well as domesticated geese and ducks. Migrating and captive waterfowl play a role in the dynamics and epidemiology of some viruses that also infect humans, such as influenza virus and West Nile virus. Crowded farm conditions favor the transmission of infectious disease agents among birds. Disease transmission is further facilitated by the comingling of wild anatids with nonmigratory resident waterfowl flocks in zoological parks or on farms. The following article will emphasize the most important viral diseases of waterfowl and briefly cover the newer diseases of suspected viral etiology in this group of birds. As viral detection and identification techniques become more and more sophisticated, and as the study of wildlife diseases increases, new viruses will be discovered and new diseases will be encountered. More research into the viral diseases of waterfowl is needed; the implementation of the latest techniques in molecular epidemiology in addition to the “gold standard” techniques such as virus isolation and histopathology, will yield insight into how viruses move from species to species and from region to region.     

甲型流感病毒多功能蛋白质NS1的研究进展

近年来大量的研究结果表明,甲型流感病毒的非结构蛋白质1(NS1)是在感染病毒期间具有多个辅助功能的毒力因子,为揭示该人畜共患病毒的致病性机理提供重要参考价值。这篇文章综述了该病毒蛋白质一些最新研究进展,包括NS1的合成、结构、亚细胞定位及在病毒复制机制、宿主天然免疫应答或/和适应性免疫应答、细胞信号传导中发挥各种作用。作者重点阐述了NS1-RNA之间和NS1-蛋白质之间的相互作用,因为它们都是上述功能和过程的基础。同时突出不同毒株NS1蛋白可能特有的特性,鉴于此,也讨论了NS1对人和动物甲型流感病毒致病性的某些作用。最后概述NS1可能应用于流感疫苗的研制、新抗病毒药物的研发等。同时比较了乙、丙型流感病毒NS1研究新进展。     

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.