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Virus nomenclature below the species level: A standardized nomenclature for filovirus strains and variants rescued from cDNA

Authors:
Jens H. Kuhn at NIH/NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick)
Jens H. Kuhn
  • NIH/NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick)
Yiming Bao at China National Center for Bioinformation
Yiming Bao
  • China National Center for Bioinformation
Sina Bavari
Sina Bavari
Stephan Becker
Stephan Becker
Stephan Becker
  • This person is not on ResearchGate, or hasn't claimed this research yet.
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Abstract

Specific alterations (mutations, deletions, insertions) of virus genomes are crucial for the functional characterization of their regulatory elements and their expression products, as well as a prerequisite for the creation of attenuated viruses that could serve as vaccine candidates. Virus genome tailoring can be performed either by using traditionally cloned genomes as starting materials, followed by site-directed mutagenesis, or by de novo synthesis of modified virus genomes or parts thereof. A systematic nomenclature for such recombinant viruses is necessary to set them apart from wild-type and laboratory-adapted viruses, and to improve communication and collaborations among researchers who may want to use recombinant viruses or create novel viruses based on them. A large group of filovirus experts has recently proposed nomenclatures for natural and laboratory animal-adapted filoviruses that aim to simplify the retrieval of sequence data from electronic databases. Here, this work is extended to include nomenclature for filoviruses obtained in the laboratory via reverse genetics systems. The previously developed template for natural filovirus genetic variant naming, ( /) / / / - , is retained, but we propose to adapt the type of information added to each field for cDNA clone-derived filoviruses. For instance, the full-length designation of an Ebola virus Kikwit variant rescued from a plasmid developed at the US Centers for Disease Control and Prevention could be akin to "Ebola virus H.sapiens-rec/COD/1995/Kikwit-abc1" (with the suffix "rec" identifying the recombinant nature of the virus and "abc1" being a placeholder for any meaningful isolate designator). Such a full-length designation should be used in databases and the methods section of publications. Shortened designations (such as "EBOV H.sap/COD/95/Kik-abc1") and abbreviations (such as "EBOV/Kik-abc1") could be used in the remainder of the text, depending on how critical it is to convey information contained in the full-length name. "EBOV" would suffice if only one EBOV strain/variant/isolate is addressed.
Kuhn et al. ArchVirol 159-1229-1237-20
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... The Filoviridae family is divided into three genera: Ebolavirus, Marburgvirus, and Cuevavirus. The genus Ebolavirus contains five distinct species, namely, Zaire ebolavirus, Sudan ebolavirus, Taï forest ebolavirus, Bundibugyo ebolavirus, and Reston ebolavirus, which is represented by EBOV, Sudan virus (SUDV), Taï forest virus, Bundibugyo virus (BDBV), and Reston virus, respectively [78]. In the most recent decade, EBOV, SUDV, and BDBV have produced Ebola virus disease (EVD) epidemics in Central and West Africa with increased frequency, and the case fatality rates range from 30% to 90% [79]. ...
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  • Nov 2022
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... The Filoviridae family is divided into three genera: Ebolavirus, Marburgvirus, and Cuevavirus. The genus Ebolavirus contains five distinct species, namely, Zaire ebolavirus, Sudan ebolavirus, Taï forest ebolavirus, Bundibugyo ebolavirus, and Reston ebolavirus, which is represented by EBOV, Sudan virus (SUDV), Taï forest virus, Bundibugyo virus (BDBV), and Reston virus, respectively [78]. In the most recent decade, EBOV, SUDV, and BDBV have produced Ebola virus disease (EVD) epidemics in Central and West Africa with increased frequency, and the case fatality rates range from 30% to 90% [79]. ...
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Article
Full-text available
  • Nov 2022
Population growth and industrialization have led to a race for greater food and supplyproductivity. As a result, the occupation and population of forest areas, contact with wildlife andtheir respective parasites and vectors, the trafficking and consumption of wildlife, the pollution ofwater sources, and the accumulation of waste occur more frequently. Concurrently, the agriculturaland livestock production for human consumption has accelerated, often in a disorderly way, leadingto the deforestation of areas that are essential for the planet’s climatic and ecological balance. Theeffects of human actions on other ecosystems such as the marine ecosystem cause equally seriousdamage, such as the pollution of this habitat, and the reduction of the supply of fish and otheranimals, causing the coastal population to move to the continent. The sum of these factors leadsto an increase in the demands such as housing, basic sanitation, and medical assistance, makingthese populations underserved and vulnerable to the effects of global warming and to the emergenceof emerging and re-emerging diseases. In this article, we discuss the anthropic actions such asclimate changes, urbanization, deforestation, the trafficking and eating of wild animals, as well asunsustainable agricultural intensification which are drivers for emerging and re-emerging of zoonoticpathogens such as viral (Ebola virus, hantaviruses, Hendravirus, Nipah virus, rabies, and severeacute respiratory syndrome coronavirus disease-2), bacterial (leptospirosis, Lyme borreliosis, andtuberculosis), parasitic (leishmaniasis) and fungal pathogens, which pose a substantial threat to theglobal community. Finally, we shed light on the urgent demand for the implementation of the OneHealth concept as a collaborative global approach to raise awareness and educate people about thescience behind and the battle against zoonotic pathogens to mitigate the threat for both humansand animals.
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Article
Full-text available
  • May 2022
  • INT J MOL SCI
MicroRNAs (miRNAs) are important gene regulatory molecules involved in a broad range of cellular activities. Although the existence and functions of miRNAs are clearly defined and well established in eukaryotes, this is not always the case for those of viral origin. Indeed, the existence of viral miRNAs is the subject of intense controversy, especially those of RNA viruses. Here, we characterized the miRNA transcriptome of cultured human liver cells infected or not with either of the two Ebola virus (EBOV) variants: Mayinga or Makona; or with Reston virus (RESTV). Bioinformatic analyses revealed the presence of two EBOV-encoded miRNAs, miR-MAY-251 and miR-MAK-403, originating from the EBOV Mayinga and Makona variants, respectively. From the miRDB database, miR-MAY-251 and miR-MAK-403 displayed on average more than 700 potential human host target candidates, 25% of which had a confidence score higher than 80%. By RT-qPCR and dual luciferase assays, we assessed the potential regulatory effect of these two EBOV miRNAs on selected host mRNA targets. Further analysis of Panther pathways unveiled that these two EBOV miRNAs, in addition to general regulatory functions, can potentially target genes involved in the hemorrhagic phenotype, regulation of viral replication and modulation of host immune defense.
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... Of the 5 Ebola species known to date, 4, including the Sudan Ebola, Zaire Ebola, Bundibugyo Ebola, and Tai Forest Ebola viruses, are the known causes of epidemics in humans. 72 More than 20 outbreaks of Ebola disease have been identified in sub-Saharan Africa, mainly due to the Zaire and Sudan viruses. The largest outbreak occurred during 2013 to 2016 in West Africa, predominantly affecting Guinea, Sierra Leone, and Liberia. ...
Prevention of Emerging Infections in Children
Article
  • Feb 2022
  • Pediatr Clin
Prevention of emerging infections in children is a dynamic arena where substantial medical advances have enabled intervention and prevention of infection outbreaks. This article discusses 5 infections causing significant morbidity and mortality across Asia, Latin America, and Africa. Avian influenza and the Middle East respiratory syndrome are highly contagious zoonoses spread through aerosol and droplets, affecting predominantly Asia. Dengue infection and chikungunya are endemic mosquito-borne viruses in tropical regions across Asia, Latin America, and Africa. Ebola is a highly contagious virus spread through human-to-human contact. The latest information in clinical manifestations, infection, prevention control, chemoprophylaxis, vaccination, and public health measures is reviewed.
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Altered microRNA Transcriptome in Cultured Human Liver Cells upon Infection with Ebola Virus
Article
Full-text available
  • Apr 2021
  • INT J MOL SCI
Ebola virus (EBOV) is a virulent pathogen, notorious for inducing life-threatening hemorrhagic fever, that has been responsible for several outbreaks in Africa and remains a public health threat. Yet, its pathogenesis is still not completely understood. Although there have been numerous studies on host transcriptional response to EBOV, with an emphasis on the clinical features, the impact of EBOV infection on post-transcriptional regulatory elements, such as microRNAs (miRNAs), remains largely unexplored. MiRNAs are involved in inflammation and immunity and are believed to be important modulators of the host response to viral infection. Here, we have used small RNA sequencing (sRNA-Seq), qPCR and functional analyses to obtain the first comparative miRNA transcriptome (miRNome) of a human liver cell line (Huh7) infected with one of the following three EBOV strains: Mayinga (responsible for the first Zaire outbreak in 1976), Makona (responsible for the West Africa outbreak in 2013–2016) and the epizootic Reston (presumably innocuous to humans). Our results highlight specific miRNA-based immunity pathways and substantial differences between the strains beyond their clinical manifestation and pathogenicity. These analyses shed new light into the molecular signature of liver cells upon EBOV infection and reveal new insights into miRNA-based virus attack and host defense strategy.
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Article
Full-text available
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Metagenomic sequencing has revolutionized our understanding of microbiology. While metagenomic tools and approaches have been extensively evaluated and benchmarked, far less attention has been given to the reference sequence database used in metagenomic classification. Issues with reference sequence databases are pervasive. Database contamination is the most recognized issue in the literature; however, it remains relatively unmitigated in most analyses. Other common issues with reference sequence databases include taxonomic errors, inappropriate inclusion and exclusion criteria, and sequence content errors. This review covers ten common issues with reference sequence databases and the potential downstream consequences of these issues. Mitigation measures are discussed for each issue, including bioinformatic tools and database curation strategies. Together, these strategies present a path towards more accurate, reproducible and translatable metagenomic sequencing.
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Naïve antibody library derived monoclonal antibody against VP35 of Ebola virus
Article
  • Jun 2023
  • INT J BIOL MACROMOL
Ebola virus is notorious for causing severe and even deadly haemorrhagic fever in infected humans and non-human primates. The high fatality rate of Ebola virus disease (EVD) has highlighted the need for effective diagnosis and treatment. Two monoclonal antibodies (mAbs) have been approved by USFDA for treatment of EVD. Virus surface glycoprotein is the common target for diagnostic and therapy including vaccines. Even so, VP35, a viral RNA polymerase cofactor and interferon inhibitor could be a potential target to curb EVD. The present work describes the isolation of three mAb clones from a phage-displayed human naïve scFv library against recombinant VP35. The clones showed binding against rVP35 in vitro and inhibition of VP35 in luciferase reporter gene assay. Structural modelling analysis was also carried out to identify the binding interactions involved in the antibody-antigen interaction model. This allows some insight into the "fitness" of the binding pocket between the paratope and target epitope which would be useful for the design of new mAbs through in silico means in the future. In conclusion, the information obtained from the 3 isolated mAbs could be potentially useful in the quest to improve VP35 targeting for therapeutic development in the future.
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Mechanisms of Immune Evasion by Ebola Virus
Chapter
  • Oct 2021
  • ADV EXP MED BIOL
The 2013–2016 Ebola virus epidemic in West Africa, which also spread to the USA, UK and Europe, was the largest reported outbreak till date (World Health Organization. 2016. https://apps.who.int/iris/bitstream/handle/10665/208883/ebolasitrep_10Jun2016_eng.pdf;jsessionid=8B7D74BC9D82D2BE1B110BAFFAD3A6E6?sequence=1). The recent Ebola outbreak in the Democratic Republic of the Congo has raised immense global concern on this severe and often fatal infection. Although sporadic, the severity and lethality of Ebola virus disease outbreaks has led to extensive research worldwide on this virus. Vaccine (World Health Organization. 2016. https://www.who.int/en/news-room/detail/23-12-2016-final-trial-results-confirm-ebola-vaccine-provides-high-protection-against-disease; Henao-Restrepo et al. Lancet 389:505–518, 2017) and drug (Hayden. Nature, 557, 475–476, 2018; Dyall et al. J Infect Dis 218(suppl_5), S672–S678, 2018) development efforts against Ebola virus are research hotspots, and a few approved therapeutics are currently available (Centers for Disease Control and Prevention. 2021. https://www.cdc.gov/vhf/ebola/clinicians/vaccine/index.html; Centers for Disease Control and Prevention. 2021. https://www.cdc.gov/vhf/ebola/treatment/index.html). Ebola virus has evolved several mechanisms of host immune evasion, which facilitate its replication and pathogenesis. This chapter describes the Ebola virus morphology, genome, entry, replication, pathogenesis and viral proteins involved in host immune evasion. Further understanding of the underlying molecular mechanisms of immune evasion may facilitate development of additional novel and sustainable strategies against this deadly virus.
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Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines
Article
Full-text available
  • May 2021
Ebola virus (EBOV) glycoprotein (GP) can be recognized by neutralizing antibodies (NAbs) and is the main target for vaccine design. Here, we first investigate the contribution of the stalk and heptad repeat 1-C (HR1C) regions to GP metastability. Specific stalk and HR1C modifications in a mucin-deleted form (GPΔmuc) increase trimer yield, whereas alterations of HR1C exert a more complex effect on thermostability. Crystal structures are determined to validate two rationally designed GPΔmuc trimers in their unliganded state. We then display a modified GPΔmuc trimer on reengineered protein nanoparticles that encapsulate a layer of locking domains (LD) and a cluster of helper T-cell epitopes. In mice and rabbits, GP trimers and nanoparticles elicit cross-ebolavirus NAbs, as well as non-NAbs that enhance pseudovirus infection. Repertoire sequencing reveals quantitative profiles of vaccine-induced B-cell responses. This study demonstrates a promising vaccine strategy for filoviruses, such as EBOV, based on GP stabilization and nanoparticle display. Ebola virus glycoprotein (GP) is a major target for vaccine design. Here, the authors identify mutations to improve GP stability and yield, design two multilayered nanoparticle carriers, and demonstrate good immunogenicity of the modified GP on nanoparticles in mice and rabbits.
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Effective countermeasure for Filovirus infections: focusing monoclonal antibodies as passive prophylaxis shield against Ebola Virus disease.
Article
  • Aug 2020
In 2020 the pandemic of COVID 19 by SARS-COV 2 infected more than 27 million with more than 875,000 deaths. Present day world is more compact with quick mode of transport between far locations, this makes spread of new viral infections at alarming rates. Similarly, Filovirus is a family of extremely dangerous Marburgvirus and Ebolavirus with up to 90% mortality rate. Since first Filovirus was discovered in 1967, many outbreaks were reported from African countries. Increased number of infected human population in other outbreaks in 2014 – 2017 poses a question of our understanding of Filovirus reservoirs. We are beginning to understand the relation between virus and ecological agents and their role in the spread of disease, but it is still a long road ahead. To counteract and containment of Filovirus infection, it is utmost requirement to understand the viral life cycle patterns, agents involved and type of circulating strains in different geographical locations. This information will provide the basis to develop viable therapies to counteract future outbreaks. In these outbreaks’ magnitude of population and geographical area affected creates the urgency to generate effective vaccines and prophylactic agents so that mortalities can be controlled during future outbreaks. Therapies are required for pre-infection acute phase and post-infection. Here, we summarize recent advances in immunotherapy strategies that can be used as passive prophylaxis. We focused on development of recent monoclonal antibodies and cocktails that can be used as neutralizing agents or immunotherapy for Ebola infected patients During the pre-outbreak period it is required to vaccinate susceptible populations that will allow limiting the infection and mortalities. Furthermore, during the acute phase to neutralize virus and limiting disease symptoms, passive prophylaxis mean neutralizing antibodies are required. In the recent past few promising therapies are developed, some of these are on the clinical trial phase. Here we will review these therapies with their advantages in protecting against Filovirus.
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Passage of Marburg Virus in Guinea Pigs
Chapter
  • Jan 1971
Following the outbreak of a mysterious disease among laboratory workers handling Cercopithecus tissue in Frankfurt and Marburg, and at the request of WHO, infectious materials were sent to us to determine whether the causal agent could be yellow fever or another arbovirus.
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Should all other biologists follow the lead of virologists and stop italicizing the names of living organisms? A proposal
Article
  • May 2009
As thousands of viruses were discovered over the years, they were given common names in English and in other languages. Then, about 20 years ago, the category "species" was introduced in virology and the vernacular names of viruses were adopted for use as species nomina and were italicized to indicate that they then referred to taxonomic entities. As a result, virologists should write that a patient was infected "with measles virus" but not "with the species Measles virus" nor with "the genus Morbillivirus", since taxonomic classes cannot cause infections. In other fields of biology the great majority of organisms only have Latin species nomina, written in italics, and no vernacular name. As a result, it will be said that a patient was infected with Bacillus anthracis, as though that taxonomic entity were able to cause a disease. What is meant, of course, is that the infection was caused by a bacterium that is a member of the species Bacillus anthracis. Attributing the infection to a species instead of an organism arises because of the absence of vernacular names for many organisms. However, this logical muddle could be avoided if the writer would use the species nomina of the disease-causing organisms but wrote them in unitalicized Roman letters, as is done with viruses. To do away with logically ill-formed statements, we propose that the names of all biological entities for which there is no common name be derived from the species nomen but written in unitalicized Roman letters. The italicized style would then be reserved for the species to which the entity belongs.
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VERVET MONKEY DISEASE TRANSMISSION TO THE HAMSTER
Article
.-Vervet monkey disease has been successfully transmitted to hamsters but only after at least 9 consecutive hamster passages following initial inoculation of monkey material previously passages 9 times in guinea-pigs and 3 times in monkeys. A uniformly fatal illness was produced in suck-ling hamsters at the 9th passage level. The disease in hamsters can be distinguished from that produced in guinea-pigs and monkeys in that it produces signs of encephalitis and the brain con-tains high levels of the infective agent. THE successful transmission of the vervet monkey disease (VMD) agent to guinea-pigs has been reported by several laboratories (Smith, Simpson,, 1968; May and Knothe, 1968). The agent has also been transmitted to monkeys (Simpson, Bowlen and Bright, 1968a; Simpson, Zlotnik and Rutter, 1968b; Haas, Maass, Muller and Oehlert, 1968) and typical intracytoplasmic inclusion bodies seen in tissue culture (Zlotnik and Simpson, 1968; Zlotnik, Simpson, Bright, Bowen and Batter-Hatton, 1968; Malherbe and Strickland-Cholmley, 1968). Cytopathic changes have been reported by Kissling, Robinson, Murphy and Whitfield (1968) but tissue culture has not been found to be a reliable monitoring or titration system. It was felt that a need existed for the establishment of the disease in a less expensive laboratory animal. This paper reports the successful transmission and adaptation of the disease to hamsters.
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Ein mauspathogener Stamm des „Marburg-Virus“ (Rhabdovirus simiae)
Article
  • Jun 1970
After three passages in baby hamsters intracerebral inoculation of Marburg virus (Rhabdovirus simiae) strain F into newborn mice resulted in the occurrence of a fatal terminating encephalitis. During further succesive passages in suckling mice virulence of the pathogenic agent increased and from brains of infected animals maximum amounts of virus (104.5 LD50 and 105.5 LD50 in passage 6 and 8, respectively) were recovered 7 days post inoculation. Adult mice, however, proved to be insusceptible. In both immunofluorescent studies and complement fixation tests the mouse pathogenic virus and Marburg virus showed identical characteristics. Moreover, pathogenicity of strain F for guinea pigs as well as cytopathogenicity of the virus for human embryonic lung fibroblasts (strain ELF) apparently were not changed during passage in hamsters and mice.
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Antigen-Nachweis des „Marburg-Virus” in den Organen infizierter Meerschweinchen durch Immunfluoreszenz
Article
  • Mar 1968
Die direkte Immunfluoreszenz-Methode wurde angewandt, um in den Organen von Meerschweinchen, die mit dem „Marburg-Virus” infiziert waren, das Erregerantigen nachzuweisen und zu lokalisieren. Bei Färbungen mit Konjugaten von vier verschiedenen Rekonvaleszenten-Seren und von einem Meerschweinchen-Immunserum konnten intra- und extrazellulär gelegene Antigenstrukturen von unterschiedlicher Form und Größe mit Durchmessern zwischen weniger als 1 μ bis 5 μ und gelegentlich 10 μ dargestellt werden. Das intrazelluläre Antigen war ausschließlich im Zytoplasma lokalisiert. Wir konnten Antigen in Lebern, Milzen, Lungen, Hoden und im Peritonealexsudat der infizierten Tiere nachweisen. Der Antigengehalt der Organe stieg mit zunehmender Adaptierung des Erregers an den Wirt im Verlauf der ersten Meerschweinchen-Passagen stark an. Die Immunfluoreszenz lieferte weiterhin einen wesentlichen Beitrag zur serologischen Identifizierung des Erregers. Mit den Konjugaten von vier verschiedenen Rekonvaleszenten-Seren ließen sich stets die gleichen Antigenstrukturen anfärben. Färbungen mit einem Meerschweinchen-Immunserum, welches von der Arbeitsgruppe um C. E. Gordon-Smith in Porton/England hergestellt und von uns mit Fluorescein konjugiert wurde, führten zu den gleichen Resultaten. Da wir überdies auch in den Tests von einem der in Frankfurt von May und Knothe infizierten Meerschweinchen Antigen nachgewiesen haben, kann die Identität der in Marburg/L., Porton und Frankfurt/M. unabhängig voneinander gewonnenen Isolate als gesichert angesehen werden. Summary Direct immunofluorescence demonstrated and localized the antigen of the causative microorganism in the organs of guinea-pigs infected by the “Marburg virus”. Staining with conjugates of four different convalescent sera and of an immune serum from one guinea-pig demonstrated intra- and extra-cellular antigens of different form and size, their diameter ranging from 1 to 5 μ and occasionally even 10 μ. The intra-cellular antigen was always located in the cytoplasm. Antigens were present in liver, spleen, lungs, scrotum and the peritoneal exudate of infected animals. The antigen content of the organs increased with increasing adaptation of the causative organism to the host and in the course of the first guinea-pig passage. The conjugates of the four different convalescent sera always stained the same antigen structure. Staining with a guinea-pig immune serum, obtained from C. E. Gordon-Smith (Porton, England) and his collaborators and conjugated by us with fluorescein gave the same results. Antigens were also demonstrated in one of the guinea-pigs infected in Frankfurt by May and Knothe: the independently isolated organisms in Marburg, Porton and Frankfurt are presumed to be identical. Resumen Comprobación por inmunofluorescencia del antígeno del “virus de Marburgo” en los órganos del conejillo de Indias infectado Con objeto de comprobar y localizar el antígeno del agente provocador en los órganos de conejillos de Indias infectados con el “virus de Marburgo”, se empleó el método directo de inmunofluorescencia. En coloraciones con conjugados de cuatro sueros diferentes de reconvalecientes y de un inmunosuero de conejillo de Indias se pudieron exponer las estructuras intra y extracelular del antígeno de diferente forma y tamaño con un diámetro de, por lo menos, 1 μ a 5 μ y, ocasionalmente, 10 μ. El antígeno intracelular se hallaba localizado exclusivamente en el citoplasma. Nosotros pudimos comprobar antígenos en el hígado, bazo, pulmones, testículos y exudado peritoneal de los animales infectados. El contenido de antígeno de los órganos crecía intensamente en el curso de los primeros pases en conejillos de Indias a medida que aumentaba la adaptación del agente provocador en el huésped. La inmunofluorescencia sigue siendo una aportación esencial para la identificación serológica del agente provocador. Con los conjugados de cuatro sueros diferentes de reconvalecientes se pudieron colorear siempre las mismas estructuras del antígeno. Coloraciones con un inmunosuero de conejillos de Indias, que fue preparado por el equipo de trabajo de C. E. Gordon-Smith en Porton/Inglaterra y conjugado con fluoresceína por nosotros, condujeron a los mismos resultados. Como aquí, además, hemos comprobado antígenos en el test de uno de los conejillos de Indias infectados en Francfort por May y Knothe, puede admitirse con seguiridad la identidad de los gérmenes aislados, independientes unos de otros, en Marburgo/L, Porton y Francfort/M.
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Bakteriologisch-virologische Untersuchungen über die in Frankfurt/M. aufgetretenen menschlichen Infektionen durch Meerkatzen
Article
  • Mar 1968
Die bakteriologischen, virologischen und morphologischen Untersuchungen bei dem durch Meerkatzen eingeschleppten Erreger werden beschrieben. Bei Meerschweinchen kann durch Patientenmaterial eine in Passagen übertragbare, tödlich verlaufende Krankheit ausgelöst werden. Filtrationsversuche ergeben einen Erreger zwischen 450—1000 mμ. Der Erreger ließ sich weder im bebrüteten Hühnerei noch in den gängigen Gewebekulturarten in drei Passagen mit zytophathischem Effekt anzüchten. Elektronenoptisch konnten aus dem Blut infizierter Meerschweinchen gewundene oder hufeisenförmig gebogene Erreger von unterschiedlicher Länge, im Durchschnitt von etwa 8000—10 000 Å, nachgewiesen werden. Von der fünften Kulturpassage an kam es zu einer Vermehrung des Erregers im menschlichen Amniongewebe. Summary Bacteriological, virological and morphological investigations of the causative organism concerned in the monkey-transmitted disease in Marburg and Frankfurt ("Marburg virus") are described. Patient material passed through guinea-pigs produced a fatal illness in them. Filtration tests showed the virus to be 450—1000 mμ. in diameter. Three passages in incubated chicken eggs and the usual tissue cultures failed to produce a cytopathic effect. Electron-microscopy revealed winding or horseshoe-shaped micro-organism within the blood of affected guinea-pigs, 8000—10,000 Å in diameter. From the fifth passage in human amnion tissue onwards there was evidence of multiplication by the micro-organism Resumen Exploraciones viro-bacteriológicas sobre las infecciones en seres humanos aparecidas en Francfort del Meno por macacos Se describen las exploraciones morfológicas, virológicas y bacteriológicas en el agente provocador introducido por el macaco. En conejillos de Indias puede desencadenarse, por material de pacientes, una enfermedad transmisible en pases y de curso mortal. Las pruebas de filtración muestran un agente provocador de 450—1000 mμ. Este agente no se puede cultivar en huevos de gallina incubados ni en las formas corrientes de cultivo tisular en tres pases con efecto citofático. Por óptica electrónica pudieron demostrarse en la sangre de conejillos de indias infectados agentes provocadores retorcidos o arqueados en forma de herradura de diferente longitud, por término medio de unos 8000—10 000 Å. A partir del quinto pase de cultivo sobreviene una multiplicación del agente provocador en el tejido amniótico humano.
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Zur Ätiologie einer unbekannten von Affen ausgegangenen Infektionskrankheit. Dtsch Med Wochenschr 92: 2341-2343
Article
  • Dec 1967
Es wird über die Isolierung, Identifizierung und Darstellung des Erregers einer bisher unbekannten, kürzlich von Affen ausgegangenen menschlichen Infektionskrankheit berichtet. Zusätzliche Angabenfolgen in einer späteren Mitteilung. Summary A number of laboratory technicians and animal-house attendants at the Behringwerke in Marburg and the Paul-Ehrlich Institute in Frankfurt, in contact with monkeys, their blood or tissues, contracted an infection similar to “haemorrhagic fever”, but differing from it in several important aspects. Isolation, identification and structure of the causative virus (“Marburg virus”) of this previously unknown disease are reported. Resumen Acerca de la etiología de una enfermedad infecciosa transmitida del mono al hombre Se informa sobre el aislamiento, identificación y presentación del agente patógeno productor de una enfermedad infecciosa, hasta ahora desconocida, recientemente transmitida del mono a las personas. En una información posterior se comunicarán datos complementarios.
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