scholarly journals Genomic characterization of serial-passaged Ebola virus in a boa constrictor cell line

2016 ◽  
Author(s):  
Greg Fedewa ◽  
Sheli R. Radoshitzky ◽  
Xiǎolì Chī ◽  
Lián Dǒngb ◽  
Melissa Spear ◽  
...  
Keyword(s):  
Cell Line ◽  
Ebola Virus ◽  
Cytopathic Effect ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Marburg Virus ◽  
Boa Constrictor ◽  
Genomic Adaptation ◽  
Genomic Characterization

ABSTRACTEbola virus disease (EVD) is a viral hemorrhagic fever with a high case-fatality rate in humans. EVD is caused by four members of the filoviral genusEbolavirus, with Ebola virus (EBOV) being the most notorious one. Although bats are discussed as potential ebolavirus reservoirs, limited data actually support this hypothesis. Glycoprotein 2 (GP2) of reptarenaviruses, known to infect only boa constrictors and pythons, are similar in sequence and structure to ebolaviral glycoprotein 2 (GP2), suggesting that EBOV may be able to infect snake cells. We therefore serially passaged EBOV and a distantly related filovirus, Marburg virus (MARV), in the boa constrictor kidney cell line, JK, and characterized viral growth and mutational frequency by sequencing. We observed that EBOV efficiently infected and replicated in JK cells, but MARV did not. In contrast to most cell lines, EBOV infected JK cells did not result in obvious cytopathic effect (CPE). Genomic characterization of serial-passaged EBOV in JK cells revealed that genomic adaptation was not required for infection. Deep sequencing coverage (>10,000x) demonstrated the existence of only a single non-synonymous variant (EBOV glycoprotein precursor preGP T544I) of unknown significance within the viral population that exhibited a shift in frequency of at least 10% over six passages. Our data suggest that boid snake derived cells are competent for filovirus infection without appreciable genomic adaptation; that cellular filovirus infection without CPE may be more common than currently appreciated; and that there may be significant differences between the natural host spectra of ebolaviruses and marburgviruses.IMPORTANCEEbola virus (EBOV) causes a high case-fatality form of viral hemorrhagic fever. The natural reservoir of EBOV remains unknown. EBOV is distantly related to Marburg virus (MARV), which has been found in bats in the wild. The glycoprotein of a reptarenavirus known to infect boid snakes (pythons and boas) shows similarity in sequence and structure to these viruses, suggesting that EBOV and MARV may be able to infect and replicate in snake cells. We demonstrate that JK, a boa constrictor cell line, does not support MARV infection, but does support EBOV infection without causing overt cytopathic effect or the need for appreciable adaptation. These findings suggest different filoviruses may have a more diverse natural host spectra than previously thought.

scholarly journals Establishment and genomic characterization of primary salivary duct carcinoma cell line

Oral Oncology ◽  
2017 ◽  
Vol 69 ◽  
pp. 108-114 ◽  
Author(s):  
Jie Li ◽  
Yohitsugu Mitani ◽  
Pulivarthi H. Rao ◽  
Laszlo Perlaky ◽  
Bin Liu ◽  
...  
Keyword(s):  
Cell Line ◽  
Carcinoma Cell ◽  
Carcinoma Cell Line ◽  
Salivary Duct Carcinoma ◽  
Salivary Duct ◽  
Duct Carcinoma ◽  
Genomic Characterization

scholarly journals Macaque Monoclonal Antibodies Targeting Novel Conserved Epitopes within Filovirus Glycoprotein

2015 ◽  
Vol 90 (1) ◽  
pp. 279-291 ◽  
Author(s):  
Zhen-Yong Keck ◽  
Sven G. Enterlein ◽  
Katie A. Howell ◽  
Hong Vu ◽  
Sergey Shulenin ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
Virus Disease ◽  
Protective Efficacy ◽  
Hemorrhagic Fever ◽  
Marburg Virus ◽  
Human Pathogens ◽  
Content Type ◽  
The Core

ABSTRACTFiloviruses cause highly lethal viral hemorrhagic fever in humans and nonhuman primates. Current immunotherapeutic options for filoviruses are mostly specific to Ebola virus (EBOV), although other members ofFiloviridaesuch as Sudan virus (SUDV), Bundibugyo virus (BDBV), and Marburg virus (MARV) have also caused sizeable human outbreaks. Here we report a set of pan-ebolavirus and pan-filovirus monoclonal antibodies (MAbs) derived from cynomolgus macaques immunized repeatedly with a mixture of engineered glycoproteins (GPs) and virus-like particles (VLPs) for three different filovirus species. The antibodies recognize novel neutralizing and nonneutralizing epitopes on the filovirus glycoprotein, including conserved conformational epitopes within the core regions of the GP1 subunit and a novel linear epitope within the glycan cap. We further report the first filovirus antibody binding to a highly conserved epitope within the fusion loop of ebolavirus and marburgvirus species. One of the antibodies binding to the core GP1 region of all ebolavirus species and with lower affinity to MARV GP cross neutralized both SUDV and EBOV, the most divergent ebolavirus species. In a mouse model of EBOV infection, this antibody provided 100% protection when administered in two doses and partial, but significant, protection when given once at the peak of viremia 3 days postinfection. Furthermore, we describe novel cocktails of antibodies with enhanced protective efficacy compared to individual MAbs. In summary, the present work describes multiple novel, cross-reactive filovirus epitopes and innovative combination concepts that challenge the current therapeutic models.IMPORTANCEFiloviruses are among the most deadly human pathogens. The 2014-2015 outbreak of Ebola virus disease (EVD) led to more than 27,000 cases and 11,000 fatalities. While there are five species ofEbolavirusand several strains of marburgvirus, the current immunotherapeutics primarily target Ebola virus. Since the nature of future outbreaks cannot be predicted, there is an urgent need for therapeutics with broad protective efficacy against multiple filoviruses. Here we describe a set of monoclonal antibodies cross-reactive with multiple filovirus species. These antibodies target novel conserved epitopes within the envelope glycoprotein and exhibit protective efficacy in mice. We further present novel concepts for combination of cross-reactive antibodies against multiple epitopes that show enhanced efficacy compared to monotherapy and provide complete protection in mice. These findings set the stage for further evaluation of these antibodies in nonhuman primates and development of effective pan-filovirus immunotherapeutics for use in future outbreaks.

scholarly journals Ocular Manifestations of Ebola Virus Disease: An Ophthalmologist’s Guide to Prevent Infection and Panic

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Enzo Maria Vingolo ◽  
Giuseppe Alessio Messano ◽  
Serena Fragiotta ◽  
Leopoldo Spadea ◽  
Stefano Petti
Keyword(s):  
Ebola Virus ◽  
Virus Disease ◽  
Clinical Signs ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Ebola Virus Disease ◽  
Ocular Manifestations ◽  
Ebola Hemorrhagic Fever ◽  
Sub Saharan ◽  
The Moment

Ebola virus disease (EVD—formerly known as Ebola hemorrhagic fever) is a severe hemorrhagic fever caused by lipid-enveloped, nonsegmented, negative-stranded RNA viruses belonging to the genusEbolavirus. Case fatality rates may reach up to 76% of infected individuals, making this infection a deadly health problem in the sub-Saharan population. At the moment, there are still no indications on ophthalmological clinical signs and security suggestions for healthcare professionals (doctors and nurses or cooperative persons). This paper provides a short but complete guide to reduce infection risks.

scholarly journals Emergence of Ebola Virus Disease (EVD): Key Facts

2015 ◽  
Vol 6 (1) ◽  
pp. 35-37
Author(s):  
Md Mahfuzar Rahman ◽  
Farnaz Mehrin ◽  
Fahim Ahmed
Keyword(s):  
Ebola Virus ◽  
Virus Disease ◽  
Virus Transmission ◽  
Specific Treatment ◽  
Case Fatality ◽  
Signs And Symptoms ◽  
Hemorrhagic Fever ◽  
Ebola Virus Disease ◽  
Background Information ◽  
Global Threat

The modern emerging infection Ebola Virus Disease (EVD) is of global threat originates from Africa region. This is zoonotic and identified as human diseases or previously called Ebola hemorrhagic fever which is a highly fatal human illness where case fatality rate is found up to 90%. The virus transmission begins from wild animals to human and then spreads within population through human to human. Fruit bats are found as natural host of Ebola virus. There is no specific treatment or vaccine available in the market so far, intensive supportive care is needed for severely ill patients. This paper highlights background information, problem statement, viral characteristics, mode of transmission, signs and symptoms, prevention & vaccination. It also indicates possible actions towards prevention of transmission & personal protection.Anwer Khan Modern Medical College Journal Vol. 6, No. 1: January 2015, Pages 35-37

scholarly journals Ebola and Marburg Viruses

2011 ◽  
Vol 6 (4) ◽  
pp. 381-389 ◽  
Author(s):  
Eri Nakayama ◽  
◽  
Ayato Takada
Keyword(s):  
Nonhuman Primates ◽  
Ebola Virus ◽  
Hemorrhagic Fever ◽  
Disease Outbreak ◽  
Marburg Virus ◽  
Virus Group ◽  
Imported Cases ◽  
Control Disease ◽  
Animal Reservoirs ◽  
Biosafety Level

Ebola and Marburg viruses, members of the filovirus family, cause severe hemorrhagic fever in human and nonhuman primates and are classified as biosafety level 4 agents. No effective filovirus-specific prophylaxis or treatment is yet commercially available. Filovirus species vary genetically, with one in the Marburg virus group and five in the Ebola virus group. Epidemiological efforts to prevent outbreaks lie mainly in identifying natural animal reservoirs. Increasingly frequent outbreaks in Africa and concerns about bioterrorism and imported cases in nonendemic areas point to the importance of public health in two ways – finding strategies to control disease outbreak and developing effective vaccines and drugs.

scholarly journals Genomic Characterization of Crimean–Congo Hemorrhagic Fever Virus inHyalommaTick from Spain, 2014

2017 ◽  
Vol 17 (10) ◽  
pp. 714-719 ◽  
Author(s):  
Maria N.B. Cajimat ◽  
Sergio E. Rodriguez ◽  
Isolde U.E. Schuster ◽  
Daniele M. Swetnam ◽  
Thomas G. Ksiazek ◽  
...  
Keyword(s):  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Genomic Characterization

scholarly journals Recombinant Vesicular Stomatitis Virus Vector Mediates Postexposure Protection against Sudan Ebola Hemorrhagic Fever in Nonhuman Primates

2008 ◽  
Vol 82 (11) ◽  
pp. 5664-5668 ◽  
Author(s):  
Thomas W. Geisbert ◽  
Kathleen M. Daddario-DiCaprio ◽  
Kinola J. N. Williams ◽  
Joan B. Geisbert ◽  
Anders Leung ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Rhesus Monkeys ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
Rhesus Macaques ◽  
Hemorrhagic Fever ◽  
Marburg Virus ◽  
Ebola Hemorrhagic Fever ◽  
Zaire Ebolavirus ◽  
Vesicular Stomatitis

ABSTRACT Recombinant vesicular stomatitis virus (VSV) vectors expressing homologous filoviral glycoproteins can completely protect rhesus monkeys against Marburg virus when administered after exposure and can partially protect macaques after challenge with Zaire ebolavirus. Here, we administered a VSV vector expressing the Sudan ebolavirus (SEBOV) glycoprotein to four rhesus macaques shortly after exposure to SEBOV. All four animals survived SEBOV challenge, while a control animal that received a nonspecific vector developed fulminant SEBOV hemorrhagic fever and succumbed. This is the first demonstration of complete postexposure protection against an Ebola virus in nonhuman primates and provides further evidence that postexposure vaccination may have utility in treating exposures to filoviruses.

scholarly journals Ferrets Infected with Bundibugyo Virus or Ebola Virus Recapitulate Important Aspects of Human Filovirus Disease

2016 ◽  
Vol 90 (20) ◽  
pp. 9209-9223 ◽  
Author(s):  
Robert Kozak ◽  
Shihua He ◽  
Andrea Kroeker ◽  
Marc-Antoine de La Vega ◽  
Jonathan Audet ◽  
...  
Keyword(s):  
Animal Model ◽  
Ebola Virus ◽  
Virus Transmission ◽  
Case Fatality ◽  
Small Animal ◽  
Hemorrhagic Fever ◽  
Transmission Model ◽  
Global Public Health ◽  
Small Animal Model ◽  
Content Type

ABSTRACTBundibugyo virus (BDBV) is the etiological agent of a severe hemorrhagic fever in humans with a case-fatality rate ranging from 25 to 36%. Despite having been known to the scientific and medical communities for almost 1 decade, there is a dearth of studies on this pathogen due to the lack of a small animal model. Domestic ferrets are commonly used to study other RNA viruses, including members of the orderMononegavirales. To investigate whether ferrets were susceptible to filovirus infections, ferrets were challenged with a clinical isolate of BDBV. Animals became viremic within 4 days and succumbed to infection between 8 and 9 days, and a petechial rash was observed with moribund ferrets. Furthermore, several hallmarks of human filoviral disease were recapitulated in the ferret model, including substantial decreases in lymphocyte and platelet counts and dysregulation of key biochemical markers related to hepatic/renal function, as well as coagulation abnormalities. Virological, histopathological, and immunohistochemical analyses confirmed uncontrolled BDBV replication in the major organs. Ferrets were also infected with Ebola virus (EBOV) to confirm their susceptibility to another filovirus species and to potentially establish a virus transmission model. Similar to what was seen with BDBV, important hallmarks of human filoviral disease were observed in EBOV-infected ferrets. This study demonstrates the potential of this small animal model for studying BDBV and EBOV using wild-type isolates and will accelerate efforts to understand filovirus pathogenesis and transmission as well as the development of specific vaccines and antivirals.IMPORTANCEThe 2013-2016 outbreak of Ebola virus in West Africa has highlighted the threat posed by filoviruses to global public health. Bundibugyo virus (BDBV) is a member of the genusEbolavirusand has caused outbreaks in the past but is relatively understudied, likely due to the lack of a suitable small animal model. Such a model for BDBV is crucial to evaluating vaccines and therapies and potentially understanding transmission. To address this, we demonstrated that ferrets are susceptible models to BDBV infection as well as to Ebola virus infection and that no virus adaptation is required. Moreover, these animals develop a disease that is similar to that seen in humans and nonhuman primates. We believe that this will improve the ability to study BDBV and provide a platform to test vaccines and therapeutics.

scholarly journals Establishment and genomic characterization of the new chordoma cell line Chor-IN-1

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Roberta Bosotti ◽  
Paola Magnaghi ◽  
Sebastiano Di Bella ◽  
Liviana Cozzi ◽  
Carlo Cusi ◽  
...  
Keyword(s):  
Cell Line ◽  
Genomic Characterization
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