Filovirus RefSeq Entries: Evaluation and Selection of Filovirus Type Variants, Type Sequences, and Names

Kuhn, Jens H.; Andersen, Kristian G.; Bào, Yīmíng; Bavari, Sina; Becker, Stephan; Bennett, Richard S.; Bergman, Nicholas H.; Blinkova, Olga; Bradfute, Steven B.; Brister, J. Rodney; Bukreyev, Alexander; Chandran, Kartik; Чепурнов, А. А.; Davey, Robert A.; Dietzgen, Ralf G.; Doggett, Norman A.; Dolnik, Olga; Dye, John M.; Enterlein, Sven; Fenimore, Paul W.; Formenty, Pierre; Freiberg, Alexander N.; Garry, Robert F.; Garza, Nicole L.; Gire, Stephen K.; Gonzalez, Jean‐Paul; Griffiths, Anthony John; Happi, Christian T.; Hensley, Lisa E.; Herbert, Andrew S.; Hevey, Michael; Hoenen, Thomas; Honko, Anna N.; Ignatyev, G. M.; Jahrling, Peter B.; Johnson, Joshua C.; Johnson, Karl M.; Kindrachuk, Jason; Klenk, Hans‐Dieter; Kobinger, Gary P.; Kochel, Tadeusz J.; Lackemeyer, Matthew G.; Lackner, Daniel F.; Leroy, Eric M.; Lever, Mark S.; Mühlberger, Elke; Нетесов, С. В.; Olinger, Gene G.; Omilabu, S.A.; Palacios, Gustavo; Panchal, Rekha G.; Park, Daniel J.; Patterson, Jean L.; Pawęska, Janusz T.; Peters, C. J.; Pettitt, James; Pitt, Louise; Radoshitzky, Sheli R.; Ryabchikova, E. I.; Saphire, Erica Ollmann; Sabeti, Pardis C.; Sealfon, Rachel; Shestopalov, A. M.; Smither, Sophie J.; Sullivan, Nancy J.; Swanepoel, Robert; Takada, Ayato; Towner, Jonathan S.; Groen, G van der; Volchkov, Viktor E.; Volchkova, Valentina A.; Wahl‐Jensen, Victoria; Warren, Travis K.; Warfield, Kelly L.; Weidmann, Manfred; Nichol, Stuart T.

doi:10.3390/v6093663

Cited by 50 publications

(49 citation statements)

References 45 publications

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“…The progenitor isolate used for the initial inoculations in guinea pigs was a stock preparation from the original clinical sample that had previously been passaged once in guinea pigs and twice on VeroE6 cells. This progenitor virus was designated Sudan virus/C.porcellus-lab/SSD/ 1976/Nzara-Boneface (SUDV-p), in accordance with established guidelines (14,15). The sequence is not identical to that of wild-type SUDV; thus, the viral sequence of SUDV-p has been deposited in GenBank.…”

Section: Methodsmentioning

confidence: 99%

Development and Characterization of a Guinea Pig-Adapted Sudan Virus

Wong

Wei

et al. 2016

J Virol

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Infections with Sudan virus (SUDV), a member of the genus Ebolavirus, result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo, a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD 50 ) of 5.3 ؋ 10 ؊2 50% tissue culture infective doses (TCID 50 ), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV. IMPORTANCE A disease outbreak due to Ebola virus (EBOV), suspected to have emerged duringDecember 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus, such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of lifesaving measures against SUDV infections.

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Section: Methodsmentioning

confidence: 99%

Development and Characterization of a Guinea Pig-Adapted Sudan Virus

Wong

Wei

et al. 2016

J Virol

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“…The relative abundance of antibody glycan structures were quantified by capillary electrophoresis as previously described (28). Briefly, antibodies were digested with IDES (FabRICATOR; Genovis) to separate Fc and F(ab=) 2 , and N-linked glycans were removed using peptide-N-glycosidase F (PNGase F) (New England BioLabs). Free glycans were labeled with 50 mM 9-aminopyrene-1,4,6-trisulfonic acid (APTS) in 1.2 M citric acid and 1 M sodium cyanoborohydride in tetrahydrofuran (THF), and excess dye was removed using a size exclusion resin.…”

Section: Methodsmentioning

confidence: 99%

“…he Filoviridae family consists of a single marburgvirus species with Marburg virus (MARV) and Ravn virus (RAVV), as well as five ebolavirus species, Ebola virus (EBOV), Sudan virus (SUDV), Bundibugyo virus (BDBV), Reston virus (RESTV), and Taï Forest virus (TAFV) (1,2). Filoviruses cause lethal hemorrhagic fever in humans and nonhuman primates (NHPs), with case fatality rates of up to 90% (3,4).…”

mentioning

confidence: 99%

Pan-ebolavirus and Pan-filovirus Mouse Monoclonal Antibodies: Protection against Ebola and Sudan Viruses

Holtsberg

Shulenin

et al. 2016

J Virol

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The unprecedented 2014-2015 Ebola virus disease (EVD) outbreak in West Africa has highlighted the need for effective therapeutics against filoviruses. Monoclonal antibody (MAb) cocktails have shown great potential as EVD therapeutics; however, the existing protective MAbs are virus species specific. Here we report the development of pan-ebolavirus and pan-filovirus antibodies generated by repeated immunization of mice with filovirus glycoproteins engineered to drive the B cell responses toward conserved epitopes. Multiple pan-ebolavirus antibodies were identified that react to the Ebola, Sudan, Bundibugyo, and Reston viruses. A pan-filovirus antibody that was reactive to the receptor binding regions of all filovirus glycoproteins was also identified. Significant postexposure efficacy of several MAbs, including a novel antibody cocktail, was demonstrated. For the first time, we report cross-neutralization and in vivo protection against two highly divergent filovirus species, i.e., Ebola virus and Sudan virus, with a single antibody. Competition studies indicate that this antibody targets a previously unrecognized conserved neutralizing epitope that involves the glycan cap. Mechanistic studies indicated that, besides neutralization, innate immune cell effector functions may play a role in the antiviral activity of the antibodies. Our findings further suggest critical novel epitopes that can be utilized to design effective cocktails for broad protection against multiple filovirus species. IMPORTANCEFiloviruses represent a major public health threat in Africa and an emerging global concern. Largely driven by the U.S. biodefense funding programs and reinforced by the 2014 outbreaks, current immunotherapeutics are primarily focused on a single filovirus species called Ebola virus (EBOV) (formerly Zaire Ebola virus). However, other filoviruses including Sudan, Bundibugyo, and Marburg viruses have caused human outbreaks with mortality rates as high as 90%. Thus, cross-protective immunotherapeutics are urgently needed. Here, we describe monoclonal antibodies with cross-reactivity to several filoviruses, including the first report of a cross-neutralizing antibody that exhibits protection against Ebola virus and Sudan virus in mice. Our results further describe a novel combination of antibodies with enhanced protective efficacy. These results form a basis for further development of effective immunotherapeutics against filoviruses for human use. Understanding the cross-protective epitopes are also important for rational design of pan-ebolavirus and pan-filovirus vaccines.

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“…Ebolavirus has five species: Zaire ebolavirus with type virus Ebola virus (EBOV), Bundibugyo ebolavirus with type virus Bundibugyo virus (BDBV), Reston ebolavirus with type virus Reston virus (RESTV), Sudan ebolavirus with type virus Sudan virus (SUDV), and Taï Forest ebolavirus (also known as Cote d'Ivoire ebolavirus) with type virus Taï Forest virus (TAFV) (Kuhn et al, 2014). Among them, EBOV has up to 90% case-fatality rate in some epidemics.…”

Section: Introductionmentioning

confidence: 99%

Ebolavirus Classification Based on Natural Vectors

Zheng

Yin

Hoang

et al. 2015

DNA and Cell Biology

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According to the WHO, ebolaviruses have resulted in 8818 human deaths in West Africa as of January 2015. To better understand the evolutionary relationship of the ebolaviruses and infer virulence from the relationship, we applied the alignment-free natural vector method to classify the newest ebolaviruses. The dataset includes three new Guinea viruses as well as 99 viruses from Sierra Leone. For the viruses of the family of Filoviridae, both genus label classification and species label classification achieve an accuracy rate of 100%. We represented the relationships among Filoviridae viruses by Unweighted Pair Group Method with Arithmetic Mean (UPGMA) phylogenetic trees and found that the filoviruses can be separated well by three genera. We performed the phylogenetic analysis on the relationship among different species of Ebolavirus by their coding-complete genomes and seven viral protein genes (glycoprotein [GP], nucleoprotein [NP], VP24, VP30, VP35, VP40, and RNA polymerase [L]). The topology of the phylogenetic tree by the viral protein VP24 shows consistency with the variations of virulence of ebolaviruses. The result suggests that VP24 be a pharmaceutical target for treating or preventing ebolaviruses.

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Filovirus RefSeq Entries: Evaluation and Selection of Filovirus Type Variants, Type Sequences, and Names

Cited by 50 publications

References 45 publications

Development and Characterization of a Guinea Pig-Adapted Sudan Virus

Development and Characterization of a Guinea Pig-Adapted Sudan Virus

Pan-ebolavirus and Pan-filovirus Mouse Monoclonal Antibodies: Protection against Ebola and Sudan Viruses

Ebolavirus Classification Based on Natural Vectors

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