Co-infection by Semliki forest virus and malarial parasite modulates viral multipucation, pathogenesis and cytokines in mice

Environmental, technological and societal factors continue to have a dramatic effect on infectious diseases worldwide and are considered to be facilitating the emergence of several infectious diseases at a time. Co-infection with different species of viral and malaria infections are currently emerging problems of dual infection in the developing as well as developed countries. Understanding of interactions between the host, malaria and virus infection is of current concern and we have initiated studies to delineate the mechanisms involved during the progression of Semliki forest virus (SFV) and Plasmodium yoelii (P. yoelii) infection in mice. Enhanced virus multiplication and up-regulation of cytokine mRNA level in P. yoelii and SFV co-infected mice were observed on day 4 post-infection compared to respective controls. Collectively, our observations indicate that malaria infection may influence virus multiplication, pathogenesis and up-regulation of cytokine mRNA during co-infection in mice.     

Macaque models of human infectious disease

Macaques have served as models for more than 70 human infectious diseases of diverse etiologies, including a multitude of agents-bacteria, viruses, fungi, parasites, prions. The remarkable diversity of human infectious diseases that have been modeled in the macaque includes global, childhood, and tropical diseases as well as newly emergent, sexually transmitted, oncogenic, degenerative neurologic, potential bioterrorism, and miscellaneous other diseases. Historically, macaques played a major role in establishing the etiology of yellow fever, polio, and prion diseases. With rare exceptions (Chagas disease, bartonellosis), all of the infectious diseases in this review are of Old World origin. Perhaps most surprising is the large number of tropical (16), newly emergent (7), and bioterrorism diseases (9) that have been modeled in macaques. Many of these human diseases (e.g., AIDS, hepatitis E, bartonellosis) are a consequence of zoonotic infection. However, infectious agents of certain diseases, including measles and tuberculosis, can sometimes go both ways, and thus several human pathogens are threats to nonhuman primates including macaques. Through experimental studies in macaques, researchers have gained insight into pathogenic mechanisms and novel treatment and vaccine approaches for many human infectious diseases, most notably acquired immunodeficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV). Other infectious agents for which macaques have been a uniquely valuable resource for biomedical research, and particularly vaccinology, include influenza virus, paramyxoviruses, flaviviruses, arenaviruses, hepatitis E virus, papillomavirus, smallpox virus, Mycobacteria, Bacillus anthracis, Helicobacter pylori, Yersinia pestis, and Plasmodium species. This review summarizes the extensive past and present research on macaque models of human infectious disease.     

Host nutritional status: the neglected virulence factor

The emergence of new infectious diseases and old diseases with new pathogenic properties is a burgeoning worldwide problem. Severe acute respiratory syndrome (SARS) and acquired immune deficiency syndrome (AIDS) are just two of the most widely reported recent emerging infectious diseases. What are the factors that contribute to the rapid evolution of viral species? Various hypotheses have been proposed, all involving opportunities for virus spread (for example, agricultural practices, climate changes, rainforest clearing or air travel). However, the nutritional status of the host, until recently, has not been considered a contributing factor to the emergence of infectious disease. In this review, we show that host nutritional status can influence not only the host response to the pathogen, but can also influence the genetic make-up of the viral genome. This latter finding markedly changes our concept of host-pathogen interactions and creates a new paradigm for the study of such phenomena.     

The impact of human conflict on the genetics of Mastomys natalensis and Lassa virus in West Africa

Environmental changes have been shown to play an important role in the emergence of new human diseases of zoonotic origin. The contribution of social factors to their spread, especially conflicts followed by mass movement of populations, has not been extensively investigated. Here we reveal the effects of civil war on the phylogeography of a zoonotic emerging infectious disease by concomitantly studying the population structure, evolution and demography of Lassa virus and its natural reservoir, the rodent Mastomys natalensis, in Guinea, West Africa. Analysis of nucleoprotein gene sequences enabled us to reconstruct the evolutionary history of Lassa virus, which appeared 750 to 900 years ago in Nigeria and only recently spread across western Africa (170 years ago). Bayesian demographic inferences revealed that both the host and the virus populations have gone recently through severe genetic bottlenecks. The timing of these events matches civil war-related mass movements of refugees and accompanying environmental degradation. Forest and habitat destruction and human predation of the natural reservoir are likely explanations for the sharp decline observed in the rodent populations, the consequent virus population decline, and the coincident increased incidence of Lassa fever in these regions. Interestingly, we were also able to detect a similar pattern in Nigeria coinciding with the Biafra war. Our findings show that anthropogenic factors may profoundly impact the population genetics of a virus and its reservoir within the context of an emerging infectious disease.     

常见肝炎病毒感染性疾病相关miRNA功能研究进展

病毒感染引发的疾病一直威胁着人类健康。Mi RNA是真核生物表达的一类重要的小分子RNA,可特异性的调节基因与蛋白的表达。mi RNA的研究为病毒性疾病的发生发展提供了新思路,为目前热点研究领域。随着mi RNA的研究深入,一些病毒感染中相关mi RNA的功能也被相继报道,如有些mi RNA具有抑制病毒感染宿主细胞的功能,有些mi RNA则可促进病毒在宿主细胞中的复制,有些mi RNA却参与病毒相关疾病的发生,还有些mi RNA则可作为病毒感染性疾病的特异性生物标志物。本文主要以两种常见肝炎病毒:HBV、HCV为例来系统阐述mi RNA在病毒感染中的相关功能。     

Techniques of molecular biology in morphological diagnosis of DNA and RNA viruses

Recognition of virus structure and biology as well as the increasingly more complete understanding of pathogenesis in infectious diseases have been possible due to the rapid development of the molecular biology techniques. In the recent few years, most of the studies employing those techniques in diagnosis of infectious diseases concerned the detection of novel viruses, clarification of the virus role in diseases of unknown aetiology and determination of the effect of virus mutants on the course of the infection. The pathogenetic mechanisms of chronic infections, oncogenesis and fibrogenesis are continued to be studied. This paper presents the advantages of using in situ hybridisation in the microscopical diagnosis of viruses. Moreover, principal techniques of amplifying the level of virus detection (in situ PCR and its variants, Immunomax) have been described. Direct application of the Immunomax technique in combination with the in situ hybridisation and with immunocytochemistry have been illustrated with our own studies on tissue expression of selected DNA viruses (HBV and HCMV).     

Global mapping of infectious disease

The primary aim of this review was to evaluate the state of knowledge of the geographical distribution of all infectious diseases of clinical significance to humans. A systematic review was conducted to enumerate cartographic progress, with respect to the data available for mapping and the methods currently applied. The results helped define the minimum information requirements for mapping infectious disease occurrence, and a quantitative framework for assessing the mapping opportunities for all infectious diseases. This revealed that of 355 infectious diseases identified, 174 (49%) have a strong rationale for mapping and of these only 7 (4%) had been comprehensively mapped. A variety of ambitions, such as the quantification of the global burden of infectious disease, international biosurveillance, assessing the likelihood of infectious disease outbreaks and exploring the propensity for infectious disease evolution and emergence, are limited by these omissions. An overview of the factors hindering progress in disease cartography is provided. It is argued that rapid improvement in the landscape of infectious diseases mapping can be made by embracing non-conventional data sources, automation of geo-positioning and mapping procedures enabled by machine learning and information technology, respectively, in addition to harnessing labour of the volunteer ‘cognitive surplus’ through crowdsourcing.     

Etiological study of uveitis in young children

The etiology of acute infectious diseases accompanied by uveitis in young children has been studied. In these investigations a high degree of contamination with virus ECHO 19 in patients with acute diseases accompanied by uveitis has been revealed and the ophthal motropic properties of the virus have been experimentally established, which indicates that certain variants of virus ECHO 19 play, probably, some role in the etiology of uveitis in young children.     

线粒体自噬在感染性疾病中的作用机制研究进展

线粒体自噬作为一种选择性自噬方式是近年研究的热点。细胞通过自噬机制选择性清除受损伤或不必需的线粒体,从而维持其功能稳态。近年来,越来越多的研究聚焦于病原体通过胁迫线粒体自噬在机体感染过程中调节先天免疫信号通路,从而影响感染性疾病的进程。本文分别从线粒体自噬在病毒、细菌和真菌感染性疾病中的作用机制研究进展进行综述,以期为感染性疾病的防治提供新的指导策略。     

Recombinant vaccinia virus vaccines

Vaccinia viruses have been genetically engineered to express foreign antigens. Immunization with these chimeric viruses protects experimental animals against challenge with the relevant infectious agent. These results, together with the successful history of vaccinia virus as an immunizing agent against smallpox, provide the impetus for employing live recombinant vaccinia viruses for the immunoprophylaxis of infectious diseases of both human and veterinary importance.     

Evolution of virulence,environmental change,and the threat posed by emerging and chronic diseases

Assessments of future threats posed by infection have focused largely on zoonotic, acute disease, under the rubric “emerging diseases.” Evolutionary and epidemiological studies indicate, however, that particular aspects of infrastructure, such as protected water supplies, vector-proof housing, and health care facilities, protect against the emergence of zoonotic, acute infectious diseases. While attention in the global health community has focused on emerging diseases, there has been a concurrent, growing recognition that important chronic diseases, such as cancer, are often caused by infectious agents that are already widespread in human populations. For economically prosperous countries, the immediacy of this threat contrasts with their infrastructural protection from severe acute infectious disease. This reasoning leads to the conclusion that chronic infectious diseases pose a more significant threat to economically prosperous countries than zoonotic, acute infectious diseases. Research efforts directed at threats posed by infection may therefore be more effective overall if increased efforts are directed toward understanding and preventing infectious causes of chronic diseases across the spectrum of economic prosperity, as well as toward specific infrastructural improvements in less prosperous countries to protect against virulent, acute infectious diseases.     

Serial infection of diverse host (Mus) genotypes rapidly impedes pathogen fitness and virulence

Reduced genetic variation among hosts may favour the emergence of virulent infectious diseases by enhancing pathogen replication and its associated virulence due to adaptation to a limited set of host genotypes. Here, we test this hypothesis using experimental evolution of a mouse-specific retroviral pathogen, Friend virus (FV) complex. We demonstrate rapid fitness (i.e. viral titre) and virulence increases when FV complex serially infects a series of inbred mice representing the same genotype, but not when infecting a diverse array of inbred mouse strains modelling the diversity in natural host populations. Additionally, a single infection of a different host genotype was sufficient to constrain the emergence of a high fitness/high virulence FV complex phenotype in these experiments. The potent inhibition of viral fitness and virulence was associated with an observed loss of the defective retroviral genome (spleen focus-forming virus), whose presence exacerbates infection and drives disease in susceptible mice. Results from our experiments provide an important first step in understanding how genetic variation among vertebrate hosts influences pathogen evolution and suggests that serial exposure to different genotypes within a single host species may act as a constraint on pathogen adaptation that prohibits the emergence of more virulent infections. From a practical perspective, these results have implications for low-diversity host populations such as endangered species and domestic animals.     

植物病毒资源属性和应用基础研究进展

病毒作为地球上最简单的生命形式,通过感染人、动物和植物等寄主产生传染性疾病。与其他微生物相比,病毒具有基因组小、复制量大、遗传操作简单等特点,具有很强的生物资源属性。过去几十年,对植物病毒的研究主要集中于解析其致病机制、植物的抗性机制及如何防控植物病害。但是随着研究的深入及概念的革新,人们发现植物病毒还具有很强的生物资源属性。随着分子生物学以及基因组、转录组、蛋白组学等技术的发展,越来越多的植物病毒被发现、改造和利用。本综述着重围绕植物病毒的资源属性与病毒载体的改造利用及其在生物工程方面的应用等最新研究进展,讨论其广泛的应用前景,挖掘其资源化的潜力。     

The Role of Immunotoxic Environmental Contaminants in Facilitating the Emergence of Infectious Diseases in Marine Mammals

A series of high profile outbreaks of newly described diseases in humans, domestic animals and wildlife has attracted widespread interest in the topic of Emerging Infectious Diseases (EIDs). Marine mammals are no exception: since 1987 several mass mortalities have been observed following infection with viruses previously undescribed in the populations or species in question. As with terrestrial examples, some of these outbreaks have followed either migrations associated with large-scale ecological changes or the introduction of virus from domestic animals. However, marine mammals warrant special concern in the context of emerging infectious diseases: they typically occupy high trophic levels and can therefore be highly contaminated with immunotoxic chemicals. Persistent Organic Pollutants (POPs), including polychlorinated -biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), -dibenzofurans (PCDFs) and related compounds, are demonstrated immunotoxicants in laboratory animals, as well as marine mammals. Immunotoxic contaminants may represent a factor that facilitates disease emergence, and may lead to the creation of susceptible “reservoirs” for new pathogens in contaminated marine mammal populations. The factors underlying the emergence and exchange of pathogens among marine mammals, domestic animals, and humans demand multidisciplinary study and invite regulatory and conservation scrutiny. The complexity of this issue may be best addressed through an integrated human and ecological risk assessment framework.     

Emerging infectious diseases associated with bat viruses

Bats play important roles as pollen disseminators and pest predators. However, recent interest has focused on their role as natural reservoirs of pathogens associated with emerging infectious diseases. Prior to the outbreak of severe acute respiratory syndrome (SARS), about 60 bat virus species had been reported. The number of identified bat viruses has dramatically increased since the initial SARS outbreak, and most are putative novel virus species or genotypes. Serious infectious diseases caused by previously identified bat viruses continue to emerge throughout in Asia, Australia, Africa and America. Intriguingly, bats infected by these different viruses seldom display clinical symptoms of illness. The pathogenesis and potential threat of bat-borne viruses to public health remains largely unknown. This review provides a brief overview of bat viruses associated with emerging human infectious diseases.     

Synergism between natural products and antibiotics against infectious diseases

Antibiotics have been effective in treating infectious diseases, but resistance to these drugs has led to the emergence of new and the reemergence of old infectious diseases. One strategy employed to overcome these resistance mechanisms is the use of combination of drugs, such as β-lactams together with β-lactamase inhibitors. Several plant extracts have exhibited synergistic activity against microorganisms. This review describes in detail, the observed synergy and mechanism of action between natural products including flavonoids and essential oils and synthetic drugs in effectively combating bacterial, fungal and mycobacterial infections. The mode of action of combination differs significantly than that of the same drugs acting individually; hence isolating a single component may lose its importance thereby simplifying the task of pharma industries.     

Perspectives and hopes in infectious pathology]

Over the last few decades, changes in socio-economic conditions and social practices as well as aggressive therapy of many diseases have led to the emergence of new infectious pathologies. These new pathologies are either associated with newly identified microbial species or the emergence of known microbes which have encountered new environments in which they are able to cause disease. Recent progress has allowed us to understand the mechanisms by which these pathogens express their virulence and will certainly allow us to diagnose and treat these infections more efficiently in the future.     

Determinants of emerging and re-emerging infectious diseases.

In the 1960s and 1970s, many public health experts assumed that infectious diseases could at long last be conquered as had occurred with smallpox. In the last two decades, reports warned that infectious diseases were clearly not a problem of the past. They could not be considered as a unique or isolated event of wild and faraway regions, but penetrated every corner of the globe. Emerging infectious diseases have been recently described as clinically distinct conditions whose incidence in humans has increased regionally or worldwide within the past two decades. Emergence may be due to the introduction of new agents to or the recognition of an existing disease that has gone undetected, and re-emergence may describe the re-appearance of known diseases after a decline in incidence. In this article a global, multidisciplinary and integrated approach in different fields of demography, epidemiology, economy, ecology, anthropology and environment at science has been considered to describe the different determinants responsible for the emergence and re-emergence of infectious diseases.     

From Pasteur to genomics: progress and challenges in infectious diseases

Over the past decade, microbiology and infectious disease research have undergone the most profound revolution since the times of Pasteur. Genomic sequencing has revealed the much-awaited blueprint of most pathogens. Screening blood for the nucleic acids of infectious agents has blunted the spread of pathogens by transfusion, the field of antiviral therapeutics has exploded and technologies for the development of novel and safer vaccines have become available. The quantum jump in our ability to detect, prevent and treat infectious diseases resulting from improved technologies and genomics was moderated during this period by the greatest emergence of new infectious agents ever recorded and a worrisome increase in resistance to existing therapies. Dozens of new infectious diseases are expected to emerge in the coming decades. Controlling these diseases will require a better understanding of the worldwide threat and economic burden of infectious diseases and a global agenda.     

Proteomics for biodefense applications: progress and opportunities

The increasing threat of bioterrorism and continued emergence of new infectious diseases has driven a major resurgence in biomedical research efforts to develop improved treatments, diagnostics and vaccines, as well as increase the fundamental understanding of the host immune response to infectious agents. The availability of multiple mass spectrometry platforms combined with multidimensional separation technologies and microbial genomic databases provides an unprecedented opportunity to develop these much needed resources. An overview of current proteomic strategies applied to microbes and viruses considered potential bioterrorism agents is presented. The emerging area of immunoproteomics as applied to the development of new vaccine targets is also summarized. These powerful research approaches can generate a multitude of potential new protein targets; however, translating these proteomic discoveries to useful counter-bioterrorism products will require large collaborative research efforts across multiple basic science and clinical disciplines. A translational proteomic research paradigm illustrating this approach using influenza virus as an example is discussed.