This April newsletter covers two quite relevant issues in virology related to global health: the first, dealing with always new zoonotic infections that are emerging from the animal world to pose a threat to human kind, and the second, focused on the recent outbreak of an almost forgotten vector-borne flavivirus, i.e. Zika virus, and its potential teratogenic effects in pregnant women.
Following emergence of humans from the primate phylogenetic tree and with the hominids first and then with Neanderthal, Denisovan and Homo sapiens spreading to the planet, occupying almost all inhabitable environmental niches and submitting the order of nature to their needs, extinction of living entities started to occur in the animal and vegetal kingdom. Bucking this extinction trend, that would see the almost exclusive presence of one dominating animal species in Earth, is the continuous discovery of new living entities such as viruses, with human pathogenic potential. The bioparasitic intrinsic nature of viruses, that originated from primordial cells and organized organic matter, have shaped animal and plant evolution through millions of years by granting the virus presence either as a constitutive feature of prokaryotic and eukaryotic genomes or as mobile or transferrable elements ready to jump from one species to another.
So, no surprise if, thanks to pangenomic approaches exploiting new sequencing and bioinformatics technologies, we continuously fish out new viruses from mammalian species other than primates, but still related to us, mainly bats and rodents. These viruses have already infected or would possibly infect humans. Notwithstanding the planetary animal extinction process that already took place, bats and rodents, with a few thousand of different species each, represent still the most diversified and numerous mammals on Earth. Suffices to say that Nipah, Hendra, SARS, MERS, Ebola, two new influenza viruses, just to quote a few recent examples, emerged from bats. On the other hand many Arenaviruses and members of the Bunyaviridae e.g. those belonging to the Hantavirus genus have emerged from rodents to cause severe diseases in humans. If we then take into account the occurrence of old pandemics (AIDS, influenza) and the risk of new ones coming from the wild life (waterfowl) and from industrial activities involving man daily life (domestic birds, cattle, swine and sheep food industries) the equation of one health one world can be transferred to that of one virology one world to deem that human, veterinary, plant and environmental virology for their biological contiguity cannot be viewed as separate disciplines. The phenomenon by which animal viruses can cross the species barrier can take place by subtle changes in the viral receptor binding molecules occurring by chance mutations, especially when the cell receptor is ubiquitously represented and highly conserved as a structure (sialic acid, endopeptidase). Alternatively, the barrier species can be broken when an arthropod borne virus adapts to vectors feeding on humans, and arthropods are another example of not-extinguishing but rather expanding animal species, due to current climate changes driven by man activities (pollution, deforestation, planetary warming) and globalization effects (travelling, urbanization). The list of vectors capable of causing severe viral infections includes mosquitoes, flies, ticks, phlebotomines; the enormous variety of their respective species impinges on the necessity of thorough entomological and virological studies to assess insect distribution and competence for viral replication, identification of the animal reservoir and natural history of the infection in the different hosts.
In this issue many of these aspects will be addressed by two excellent virus hunters, who have recently collaborated within the Antigone network, supported by EU and international grants, to detect new viruses in the wild and to find the causes of new emerging viral outbreaks. Professor Albert Osterhaus, a former Director of the Erasmus Medical Center, is a vet virologist now working at the University of Veterinary Medicine in Hannover, at the Research Center for Emerging Infections and Zoonoses (RIZ). He is the co-discoverer of many new viruses and will unveil the mechanistic pathways by which viruses jump from animals to humans and from humans to animals.
Professor Christian Drosten is the Director of the Institute of Virology of the Medical Faculty of Bonn University and the co-discoverer of the SARS corona virus. He will address the relevant biomedical aspects of the recent outbreak of Zika virus, a mosquito-borne flavivirus firstly identified in Uganda in 1947. He will focus on how the virologists’ community is ready to face this new challenge.
President of the European Society for Virology
Emerging And Re-Emerging Viruses: Origins And Drivers*
Ab Osterhaus and Leslie Reperant, ‘Artemis One Health’ Utrecht, The Netherlands and ‘RIZ’, Hannover, Germany
Complex relationships between the human and animal species have never ceased to evolve since the emergence of the human species and have resulted in a human-animal interface that has promoted the cross-species transmission, emergence and eventual evolution of a plethora of infectious pathogens. Remarkably, most of the characteristics of the human-animal interface -as we know it today- have been established long before the end of our species pre-historical development took place, to be relentlessly shaped throughout the history of our species. More recently, changes affecting the modern human population worldwide as well as their dramatic impact on the global environment have taken domestication, agriculture, urbanization, industrialization, and colonization to unprecedented levels. This has created a unique global multi-faceted human-animal interface, associated with a major epidemiological transition that is accompanied by an unexpected rise of new and emerging infectious diseases. Until the beginning of the last century, infectious diseases were the major cause of mortality of humankind. Around 1900 infectious diseases caused an estimated fifty percent of all deaths in the western world. In the following decades, this percentage decreased to a few percent. This was largely due to the implementation of public health measures such as the installment of sewage and clean drinking water systems, but also to the development of vaccines and antimicrobial compounds. A major success in this regard was the eradication of smallpox through a worldwide vaccination campaign orchestrated by the World Health Organization (WHO). Stimulated by these successes certain policymakers and scientists predicted that all infectious diseases of humankind would be brought under control. Paradoxically the following decades confronted the world with an ever-increasing number of emerging or re-emerging infectious diseases, some causing true pandemics. A complex mix of predisposing factors in our globalizing world, linked to major changes in our social environment, technology and global ecology, collectively created opportunities for viruses to infect new hosts. Subsequent adaptation to the newly invaded species then paved the way for an unprecedented spread with dramatic consequences for public health, animal health, animal welfare, food supply, economies, and biodiversity. Striking examples were the emergence of AIDS, Avian flu, SARS, MERS, Ebola and most recently Zika. Viruses spilling over from animal reservoirs have all caused these disease outbreaks.
HIV, the causative agent of the AIDS pandemic that started about thirty years ago, with changes in bush meat consumption, behaviour, demography, human mobility, medical practises and rapidly adapting viruses as main drivers, has now infected more than 55 million people of whom more than 20 million have died. The identification of HIV as the causative agent took more than two years after the recognition of AIDS as a new disease entity. Since then virus discovery techniques have evolved drastically with the advent of an ever-increasing range of new generation molecular techniques. This allowed us to rapidly identify dozens of new viruses of animals and humans, some of which were indeed newly emerging viruses, while others were viruses that had just not been discovered before due to technical limitations. Avian influenza viruses were first shown to sporadically infect humans in Hong Kong in the late 90ies of the last century, without subsequent efficient human-to-human transmission. However more recently it was shown that not more than a handful of mutations would allow such avian influenza viruses to become transmissible among mammals, thus creating a pandemic threat. In the light of the four influenza pandemics that have occurred in the last century, and together have cost the lives of more than 50 million people, this is an alarming observation. The emergence of severe acute respiratory syndrome (SARS) in China at the beginning of the 21st century, proved to be caused by a newly discovered coronavirus that most probably spilled over from a bat reservoir, an was transmitted via carnivores to humans. SARS coronavirus started to spread efficiently among humans, rapidly creating a pandemic threat. Through an international WHO-coordinated collaborative pathogen discovery and intervention network, this virus was identified and characterized within a month after the start of this collaboration and the emerging pandemic was subsequently rapidly controlled. A decade later yet another coronavirus of probable bat origin spilled over to humans in the Middle East, causing Middle East respiratory syndrome (MERS). The identification and characterization of MERS coronavirus was performed in a matter of weeks, whereas the dromedary camel proved to be the intermediate species that transferred the virus to humans. Different outbreaks in the Middle East and sporadic cases and outbreaks elsewhere, have indicated predominantly nosocomial human-to-human transmission. It is not clear at present whether this virus has the potential to cause a pandemic. Most recently the emergence of Zika virus, a flavivirus that had been discovered in Africa in the middle of the last century, emerged outside Africa and Asia in the last decade. Zika virus that is transmitted by Aedes mosquitos, was initially shown to cause a mild and self-limiting disease, and was until recently considered to be a relatively innocuous pathogen. However an increased incidence of microcephaly in unborn babies that coincided since last year with the emergence of Zika virus in South America, has created an ongoing public health emergency.
Importantly, the unprecedented emergence of these and other viruses is largely paralleled by medical, technological, and scientific progress, continuously spurred by our never-ending combat against pathogens. Investment in a better understanding of the human-animal interface will therefore offer humankind a future head start in the never-ending battle against emerging infectious diseases.
*Reperant LA, Cornaglia G, Osterhaus AD. Curr Top Microbiol Immunol. 2013
Zika in Perspective
Christian Drosten, Institute of Virology, University of Bonn, Germany
Please refer to the Zika facts summary by the Society for Virology in Germany
To virologists, Zika virus is a long known subject (1). Experienced labs consider the infection among the differential diagnoses in cases of fever after travel to tropical Africa and, more lately, Asia. Reports on the occurrence of this typical Old World virus in Brazil in May 2015 were admittedly surprising, but did not come totally unexpected in light of the introduction of chikungunya virus to the Americas 1 year earlier (2). It seemed that Zika was just another aedes-transmitted and primate-associated arbovirus that made it into the virgin soil-environment of the neotropics. Ensuing reports of cases of Guillain-Barré syndrome associated with Zika virus infection caused little concern, as the syndrome is non-specifically associated with a whole range of pathogens. A whole new and very different aspect was added in October 2015, when the Brazil Ministry of Health expressed concern about an increased incidence of microcephaly in newborns in the northeastern part of the country that followed the arrival and spread of Zika virus with a delay corresponding to the duration of a human pregnancy.
Virologists know a whole number of viruses causing this and similar neurological fetopathies in humans. Rubella virus, the most notorious representative, has been virtually eliminated as a cause of fetopathy through vaccination programs in Europe and the Americas. The One Health perspective provides epidemiological scenarios not normally considered in humans. In Europe, we have just witnessed the devastating consequences of a fetopathogenic virus that is transmitted by blood-feeding insects. The Schmallenberg virus was recognized in Germany in 2011 and spread across Europe within less than 2 years, causing dramatic malformations including severe cerebral fetopathies in ruminants (3). We did not dare at that time to project an equivalent scenario for a human disease.
The threat posed by Zika virus is difficult to express in numbers. The emotional component, the uncertainty, as well as the possibility to miss a window of opportunity for study and intervention have already triggered ad-hoc funding programs and pragmatic approaches to extract information from available data. It is not in spite of the emotional component, but because of it, that virologists should look at the problem from a scientific perspective – and communicate a conservative perspective to the public via the media.
Most virus infections that cause fetopathy have a low manifestation index. Certainly, also the Zika virus will cause harm in only a small proportion of the many pregnant women now exposed to the virus. Of note, the attack rate in the 2007 outbreak on Yap island (Micronesia) may have been as high as 73% in the population aged >3 years. In the much larger outbreak in French Polynesia the attack rate was 11.5% according to retrospective analyses (1). In the affected regions in South America, where people are similarly exposed and immunologically naïve toward the infection, very high rates of unnoticed infection are to be expected – including in pregnant women. Even if truly associated with Zika virus infection, the 5640 cases of microcephaly reported in Brazil by end of February 2016 will only represent a tiny fraction of the many pregnant women who got infected during 2015. A more severe issue is the reporting and classification of microcephaly. The perception of an increased incidence of microcephaly came up in an area notably affected by Zika virus. Beginning in autumn 2015, the Brazilian MOH strengthened and emphasized microcephaly surveillance, whereas notifications prior to this time occurred on a more routine basis. The media coverage of the Zika/microcephaly connection contributed an additional stimulus for reporting. A recent research manuscript suggests that the MOH reporting criterion for suspected cases of microcephaly, based on cranial circumference of 32 cm, may be inappropriate for the most affected population in northeastern Brazil. This criterion may trigger the formal notification of up to 10% of all newborns as suspected cases of microcephaly (4). Of the 5,640 suspected cases notified so far, 3,935 remain under investigation (5). Among the remaining 1705 cases, 950 have not been confirmed as cases of microcephaly (5).
The literature now contains several reports on Zika virus detection in amniotic fluid, blood, and even central nervous tissue of fetuses with signs of microcephaly. With every new case report that is published, we perceive the link between Zika virus infection and microcephaly to become stronger. There is probably truth to this. However, as scientists we should emphasize that case reports do not establish a causative link between virus and microcephaly. As always at the beginning of epidemics, studies tend to focus on cases but not controls. What fraction of healthy pregnancies and babies might reveal evidence for Zika virus infection if sampled at the peak of an outbreak, assuming attack rates of 10% or even higher in the adult population? Up to now, 583 cases of microcephaly in Brazil have been completely investigated including objective neurological criteria and virological laboratory tests. Only 67 (11.5%) tested positive for Zika virus infection (5). An extrapolation of this proportion to all notified cases fails to explain the reported >20-fold increase of incidence of microcephaly in northeastern Brazil compared to other populations.
The increase of microcephaly may represent a complex effect on the local population that could include other factors such as unrecognized pathogens or environmental causes. These factors may manifest as microcephaly alone or in concert with Zika virus infection. The WHO Zika Open resource carries a research manuscript that follows the incidence of microcephaly from 2012 to 2015 in Paraiba, the Brazilian federal state that was second most affected (6). Using data from prospectively-designed birth cohorts, the study reveals a stark increase of microcephaly incidence already by end of 2012 and a second peak by mid 2014, pre-dating the presumed introduction of Zika virus into the country. A third peak of incidence recorded for the second half of 2015 is the strongest peak. Only this peak plausibly correlates with Zika outbreaks. We should remain open for additional or even alternative explanations for the increased incidence of microcephaly observed in northeastern Brazil. Interestingly, the outbreak in French Polynesia, which according to ongoing retrospective analyses may have involved fetopathies, co-incided with a dengue virus outbreak (1). Dengue is also endemic in many of the regions now affected by the Zika outbreak in Brazil.
Having summarized concerns regarding the true incidence of Zika-associated microcephaly, we should not forget to mention that virally-induced fetopathies can involve many other symptoms that are not easily objectified. Along with microcephaly, retinal malformations have already been noted in 2 cases (1). Zika´s association with Guillain Barré Syndrome can be regarded as confirmed based on a recent revisit of the French Polynesia outbreak (7). However, GBS should not be regarded as predictive for other severe neurological sequelae as many other pathogens that are not specifically neurotropic are associated with the syndrome (e.g., campylobacter). Co-endemic arboviroses including dengue and chikungunya virus infection are thought to trigger Guillain Barré syndrome, typically with low incidence. Much more worrying with regard to Zika virus infection is the perspective of sequelae effective on higher neurological functions, involving deficits that may come to show as kids develop. The clear reports of fetal neurotropic infection (e.g., 8) call for neuro-psychiatric follow-up of birth cohorts.
Given the epidemiological uncertainities regarding the causation of microcephaly, animal experiments will be utilized to compensate for pressing information needs. Newborn mice can be readily infected with a range of arboviruses, but the pathology observed in adult mouse models does usually not compare to the situation in primates for most human arboviruses. Mouse-adapted adult disease models for zika virus infection are not available. Even if they were, it is questionable whether these models could reliably depict syndromes that show a very low incidence among cases with normal courses of infection. Experiments on pregnant macaques are being conducted as this text is being written. However, the results of these experiments may not come in time to provide first evidence of causation of microcephaly. Nature is presenting us with a large-scale, cruel study scenario in humans. We will be able to observe over the next coming months whether the incidence of microcephaly will increase in areas that have been newly affected by Zika virus since the end of 2015. Next to the implementation of prophylactic measures such as mosquito control, it is our prime responsibility to secure epidemiological evidence by careful design of prospective, controlled obervational trials.
6th European Congress of Virology
The 6th European Congress of Virology (ECV2016) is taking shape!
The Heinrich Pette Institute – Leibniz Institute for Experimental Virology feels very honored to organize this major virology meeting in Europe on behalf of the European Society of Virology (ESV). ECV2016 will be a truly international and multidisciplinary event, covering all facets of human, veterinary and plant virology. The organizing committee is working hard to ensure a highly stimulating cross-talk of laboratory science and clinical research at ECV2016.
ECV2016 will take place at the Congress Center Hamburg (CCH) from 19th to 22nd October 2016 and will showcase an impressive line-up of internationally renowned speakers. Every conference day will be highlighted by a plenary session, featuring invited talks on current topics in virology. These include translational aspects, such as, for example, “The Future of Antiviral Therapy” or more basic research oriented themes, exemplified by the session “Animal Models for Virus Research”. Likewise, every Workshop Session will kick-off with an in depth keynote lecture, setting the stage for a number of scientific presentations selected from the abstract submissions. Notably, registration and abstract on-line submission have already started and a limited number of travel grants are available (for detailed information please refer to the ECV2016 website: www.eurovirology2016.eu). Altogether, ECV2016 will feature a total of around 50 invited Plenary and Keynote Lectures and more than 150 high-quality Workshop Presentations. The congress will also host the ceremonies of the ESV European Virology Award and the ESV Junior Investigator Award. Thus, ECV2016 will provide an outstanding professional platform for personal interaction of junior and senior virologists and clinicians alike.
And this is not all. A number of Satellite Symposia organized by scientific initiatives and ventures of the pharma/biotech sector is planned to accompany ECV2016. For example, the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) together with the German Center for Infection Research (DZIF) cooperate to organize a Satellite Symposium on ‘HIV and HBV Cure’. The symposium will be reporting on the state-of-the-art of current cure approaches and will provide a platform to discuss obstacles and aspects of future HIV and HBV cure strategies. ECV2016 will also feature an industrial exhibition, showcasing various suppliers for reagents and tools for virus research, technical equipment, diagnostics or medicines to treat virus-induced diseases. In sum, ECV2016 will showcase the latest developments in basic and translational virus research, providing best science and a great learning environment.
The Congress Center Hamburg (CCH) as meeting venue, is one of the leading congress centers in Europe and is characterized by excellent infrastructure placed right in the center of the Free and Hanseatic City of Hamburg. In fact the ECV2016 will be happening within walking distance of numerous restaurants and hotels of all categories. No need to say, that special events, such as Congress Dinner and Networking Party will further stimulate social interaction of all attendees and hopefully trigger new collaborations or businesses.
The Organizing Committee and I are looking forward to welcoming you this autumn in Hamburg to experience a few days of world-class science in this vibrant and multi-cultural capital of northern Germany.
President of ECV2016
News and Updates
European Society for Virology – Elections 2016
Three years have passed since ESV’s last elections were held in 2013. This year, it’s election year again, and all full and corporate members of the Society will be asked to elect the representatives of the Executive Board and the Advisory Council for the next term of office. Pre-Elections will be conducted electronically in the period from April to October 2016. Final elections will be held in the course of the Assembly of Members during the 6th European Congress of Virology in Hamburg in October 2016.
Dates and Procedures of the Elections 2016 – Continue Reading
4th European Seminars in Virology – Five ESV Fellowships
The European Society for Virology provides five fellowships for young scientists who are actively participating in the 4th European Seminars in Virology: Oncogenic and Oncolytic Viruses to be held from 10-12 June, 2016 in Bertinoro, Italy.
For further details see http://www.eusev2016.lima-city.de/
ECV 2016 – 20 ESV Travel Grants for Junior Scientists
The European Society for Virology offers 20 travel grants of EUR 500 each for graduate students (PhD or MD) to participate in the 6th European Congress of Virology, held from 19-22 October, 2016 in Hamburg, Germany. Candidates should not yet have completed their doctoral thesis and actively participate in the conference. Applications including the candidate’s name and current address, conference abstract, statement describing the relevance of participation in ECV 2016 for the candidate’s research project, résumé, list of publications (if applicable), and a letter of recommendation from the applicant’s doctoral thesis supervisor should be sent by email to Prof. Joachim Hauber, President of ECV 2016 (firstname.lastname@example.org). Deadline for applications is 15 June, 2016.
Awardees will be selected directly by the organizing committee of ECV 2016 based on the scientific quality and relevance of their submitted abstracts.
4th European Seminars in Virology: Viral Oncology and Virotherapy
10 – 12 June, 2016
The Topics of oncogenic but also oncolytic viruses are really actual and challenging in basic virology, medical virology, oncogenesis as well as tumor therapy. About 20% of human tumors are etiologically connected to infectious agents, primarily persisting viruses. On the other hand oncolytic viruses may open a new therapeutic option for so far not curable oncologic diseases. Topics shall be presented and discussed covering the aspects of
The principle is to favor during 2.5 days close contacts between advanced graduate students/post-docs and reputed scientists in a free and interactive atmosphere inviting to exchange and discussion.
For registration and further details see http://www.eusev2016.lima-city.de/
Please note that the registration will close on April 15.
3rd Innovative Approaches for Identification of Antiviral Agents Summer School
29 September – 2 October, 2016
Santa Margherita di Pula, Italy
This Summer School aims to provide an informal and interactive environment to review the application of high throughput screening techniques to identification of novel and clinically-significant antiviral drugs. The Summer School is targeted to researchers at an early stage in their career, combining examples of drug discovery from internationally-recognized experts in the field with informal, small-group thematic discussion sessions. Evening sessions will allow students to present their work in the form of either a poster or oral presentations and receive feedback from their colleagues.
6th European Congress of Virology
19 – 22 October, 2016
The European Congress of Virology (ECV) is the premier virology conference in Europe and is organized by the European Society for Virology. ECV2016 will bring together both junior and senior scientists, and will cover all aspects of virus research including basic, clinical, veterinary and plant virology.
Please see http://www.eurovirology2016.eu/ for more information.
Further Conferences and Events of Interest
XVIth International Parvovirus Workshop
19 – 23 June, 2016
2nd International Course on Viruses and Human Cancer
1 – 09 July, 2016
13th HKU-Pasteur Virology Course: Bats and Viruses
10 – 22 July, 2016
Hong Kong www.hkupasteur.hku.hk
Frontiers of Retrovirology 2016 – Complex Retroviruses, Retroelements and Their Hosts
12 – 14 September, 2016
© 2016 European Society for Virology
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