#Dendritic Cells Generated From Mops condylurus, a Likely #Filovirus Reservoir Host, Are Susceptible to and Activated by #Zaire #Ebolavirus Infection (Front Immunol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Front Immunol. 2019 Oct 11;10:2414. doi: 10.3389/fimmu.2019.02414. eCollection 2019.

Dendritic Cells Generated From Mops condylurus, a Likely Filovirus Reservoir Host, Are Susceptible to and Activated by Zaire Ebolavirus Infection.

Edenborough KM1, Bokelmann M1, Lander A1, Couacy-Hymann E2, Lechner J3, Drechsel O3, Renard BY3, Radonić A3, Feldmann H4, Kurth A1, Prescott J1.

Author information: 1 Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany. 2 LANADA, Laboratoire National d’Appui au Développement Agricole, Bingerville, Côte d’Ivoire. 3 Methodology and Research Infrastructure, Robert Koch Institute, Berlin, Germany. 4 Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, ON, United States.

 

Abstract

Ebola virus infection of human dendritic cells (DCs) induces atypical adaptive immune responses and thereby exacerbates Ebola virus disease (EVD). Human DCs, infected with Ebola virus aberrantly express low levels of the DC activation markers CD80, CD86, and MHC class II. The T cell responses ensuing are commonly anergic rather than protective against EVD. We hypothesize that DCs derived from potential reservoir hosts such as bats, which do not develop disease signs in response to Ebola virus infection, would exhibit features associated with activation. In this study, we have examined Zaire ebolavirus (EBOV) infection of DCs derived from the Angolan free-tailed bat species, Mops condylurus. This species was previously identified as permissive to EBOV infection in vivo, in the absence of disease signs. M. condylurus has also been recently implicated as the reservoir host for Bombali ebolavirus, a virus species that is closely related to EBOV. Due to the absence of pre-existing M. condylurus species-specific reagents, we characterized its de novo assembled transcriptome and defined its phylogenetic similarity to other mammals, which enabled the identification of cross-reactive reagents for M. condylurus bone marrow-derived DC (bat-BMDC) differentiation and immune cell phenotyping. Our results reveal that bat-BMDCs are susceptible to EBOV infection as determined by detection of EBOV specific viral RNA (vRNA). vRNA increased significantly 72 h after EBOV-infection and was detected in both cells and in culture supernatants. Bat-BMDC infection was further confirmed by the observation of GFP expression in DC cultures infected with a recombinant GFP-EBOV. Bat-BMDCs upregulated CD80 and chemokine ligand 3 (CCL3) transcripts in response to EBOV infection, which positively correlated with the expression levels of EBOV vRNA. In contrast to the aberrant responses to EBOV infection that are typical for human-DC, our findings from bat-BMDCs provide evidence for an immunological basis of asymptomatic EBOV infection outcomes.

Copyright © 2019 Edenborough, Bokelmann, Lander, Couacy-Hymann, Lechner, Drechsel, Renard, Radonić, Feldmann, Kurth and Prescott.

KEYWORDS: Ebola virus (EBOV); Mops condylurus; dendritic cells; filovirus; reservoir hosts; transcriptome

PMID: 31681302 PMCID: PMC6797855 DOI: 10.3389/fimmu.2019.02414

Keywords: Filovirus; Ebola; ZEBOV; Bats.

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Expression of #microRNA in #human #retinal pigment #epithelial cells following #infection with #Zaire #ebolavirus (BMC Res Notes, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMC Res Notes. 2019 Oct 1;12(1):639. doi: 10.1186/s13104-019-4671-8.

Expression of microRNA in human retinal pigment epithelial cells following infection with Zaire ebolavirus.

Oliver GF1, Orang AV1, Appukuttan B1, Marri S1, Michael MZ1, Marsh GA2, Smith JR3.

Author information: 1 Flinders University College of Medicine and Public Health, Flinders Medical Centre Room 4E-431, Flinders Drive, Bedford Park, SA, 5042, Australia. 2 Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation, 5 Portarlington Rd, Newcomb, VIC, 3219, Australia. 3 Flinders University College of Medicine and Public Health, Flinders Medical Centre Room 4E-431, Flinders Drive, Bedford Park, SA, 5042, Australia. justine.smith@flinders.edu.au.

 

Abstract

OBJECTIVE:

Survivors of Ebola virus disease (EVD) are at risk of developing blinding intraocular inflammation-or uveitis-which is associated with retinal pigment epithelial (RPE) scarring and persistence of live Zaire ebolavirus (EBOV) within the eye. As part of a large research project aimed at defining the human RPE cell response to being infected with EBOV, this work focused on the microRNAs (miRNAs) associated with the infection.

RESULTS:

Using RNA-sequencing, we detected 13 highly induced and 2 highly repressed human miRNAs in human ARPE-19 RPE cells infected with EBOV, including hsa-miR-1307-5p, hsa-miR-29b-3p and hsa-miR-33a-5p (up-regulated), and hsa-miR-3074-3p and hsa-miR-27b-5p (down-regulated). EBOV-miR-1-5p was also found in infected RPE cells. Through computational identification of putative miRNA targets, we predicted a broad range of regulatory activities, including effects on innate and adaptive immune responses, cellular metabolism, cell cycle progression, apoptosis and autophagy. The most highly-connected molecule in the miR-target network was leucine-rich repeat kinase 2, which is involved in neuroinflammation and lysosomal processing. Our findings should stimulate new studies on the impact of miRNA changes in EBOV-infected RPE cells to further understanding of intraocular viral persistence and the pathogenesis of uveitis in EVD survivors.

KEYWORDS: Ebola; Filovirus; Retina; Retinal pigment epithelium; Uveitis; Zaire ebolavirus; microRNA

PMID: 31570108 DOI: 10.1186/s13104-019-4671-8

Keywords: Ebola; ZEBOV; Viral pathogenesis.

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#Recombinant subunit #vaccines protect guinea pigs from lethal #Ebola virus challenge (Vaccine, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vaccine. 2019 Jul 16. pii: S0264-410X(19)30797-2. doi: 10.1016/j.vaccine.2019.06.035. [Epub ahead of print]

Recombinant subunit vaccines protect guinea pigs from lethal Ebola virus challenge.

Lehrer AT1, Wong TS2, Lieberman MM3, Johns L2, Medina L3, Feldmann F4, Feldmann H5, Marzi A6.

Author information: 1 PanThera Biopharma, LLC, Aiea, HI 96701, United States; University of Hawaii at Manoa, John A. Burns School of Medicine, Honolulu, HI 96813, United States. Electronic address: lehrer@hawaii.edu. 2 PanThera Biopharma, LLC, Aiea, HI 96701, United States; University of Hawaii at Manoa, John A. Burns School of Medicine, Honolulu, HI 96813, United States. 3 University of Hawaii at Manoa, John A. Burns School of Medicine, Honolulu, HI 96813, United States. 4 Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, United States. 5 Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, United States. 6 Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, United States. Electronic address: marzia@niaid.nih.gov.

 

Abstract

Ebola virus (EBOV) is among the deadliest pathogens known to man causing infrequent outbreaks of hemorrhagic disease. In humans, the case fatality rates in the outbreaks can reach 90%. During the West African epidemic almost 30,000 people were infected and of these over 11,000 fatalities were reported. Currently, we are facing an uncontained larger outbreak in the Democratic Republic of the Congo. Even though EBOV was discovered in 1976, extensive efforts to develop countermeasures, particularly therapeutics and vaccines, started late and there is still no FDA-approved product available. Nevertheless, one candidate vaccine, the rVSV-ZEBOV, is being used in clinical trials during the current outbreak with the hope of ending the human transmission chains. However, adverse reactions to administration of some EBOV vaccines have been reported; therefore, we have developed a safe and efficacious formulation of insect-cell derived adjuvanted protein vaccines. Vaccine candidates containing the EBOV glycoprotein with or without matrix proteins VP24 and VP40 formulated with one of three different adjuvants were tested in guinea pigs for immunogenicity and efficacy against lethal EBOV challenge. The results demonstrated that these vaccine candidates engendered high titers of antigen-specific antibodies in immunized animals and two of these vaccine candidates afforded complete or nearly complete protection against lethal challenge. Interestingly, we found a sex bias in partially protected immunized groups with male guinea pigs succumbing to disease and females surviving. In summary, we developed a safe and immunogenic adjuvanted subunit vaccine uniformly protective against EBOV disease in guinea pigs.

Copyright © 2019 Elsevier Ltd. All rights reserved.

KEYWORDS: Glycoprotein; Recombinant protein; VP24; VP40; Zaire ebolavirus

PMID: 31324500 DOI: 10.1016/j.vaccine.2019.06.035

Keywords: Ebola; ZEBOV; Vaccines; Animal models.

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The efficacy of poly-ICLC against #Ebola-Zaire virus (EZV) #infection in mice and cynomolgus #monkeys (Antiviral Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Antiviral Res. 2019 Jan 3. pii: S0166-3542(18)30407-8. doi: 10.1016/j.antiviral.2018.12.020. [Epub ahead of print]

The efficacy of poly-ICLC against Ebola-Zaire virus (EZV) infection in mice and cynomolgus monkeys.

Kende M1, Paragas J2, Salazar AM3.

Author information: 1 United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD, 21702, United States. Electronic address: meir.kende.vol@mail.mil. 2 United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD, 21702, United States. 3 Oncovir, Inc., 3203 Cleveland Avenue, Washington D.C, 20008, United States.

 

Abstract

The potential protection of poly-ICLC (Hiltonol®) a double stranded RNA (dsRNA) against EZV infection was assessed with prophylactic and therapeutic administration to wild type and TLR3-negative mice, and in non-human primates (NHPs) by measuring EZV serum titers, survival extension, and serum liver and kidney function markers. Various doses of aqueous and liposomal poly-ICLC monotherapy provided robust protection in otherwise lethal murine Ebola virus challenge models, when treatment is started on the day of -or one day after virus challenge. There was no advantage of liposomal vs. the aqueous poly-ICLC form. Protection appeared to be independent of TLR-3. NHPs treated with poly-ICLC and challenged with EZV survived longer but eventually succumbed to Ebola infection. Nevertheless, the liver and kidney serum markers were markedly reduced in the infected and treated NHPs. In the two longest surviving poly-ICLC- treated NHPs, the day 10 serum EZV titer was reduced 2.1 and 30 fold respectively.

KEYWORDS: Aqueous/liposomal poly-ICLC; Efficacy in mice; NHP EZV titers; NHP liver/kidney enzymes; NHP survival time; TLR+/ TLR-3 mice

PMID: 30611774 DOI: 10.1016/j.antiviral.2018.12.020

Keywords: Ebola; Antivirals; Animal models.

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Comparative Transcriptomics in #Ebola #Makona-Infected #Ferrets, Nonhuman #Primates, and #Humans (J Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Infect Dis. 2018 Nov 22;218(suppl_5):S486-S495. doi: 10.1093/infdis/jiy455.

Comparative Transcriptomics in Ebola Makona-Infected Ferrets, Nonhuman Primates, and Humans.

Cross RW1,2, Speranza E3, Borisevich V1,2, Widen SG4, Wood TG4, Shim RS5, Adams RD5, Gerhardt DM5, Bennett RS5, Honko AN5, Johnson JC5, Hensley LE5, Geisbert TW1,2, Connor JH4,3.

Author information: 1 Galveston National Laboratory, University of Texas Medical Branch, Galveston. 2 Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston. 3 Department of Microbiology, Bioinformatics Program, National Emerging Infectious Disease Laboratories, Boston University, Massachusetts. 4 Departments of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston. 5 Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland.

 

Abstract

The domestic ferret is a uniformly lethal model of infection for 3 species of Ebolavirus known to be pathogenic in humans. Reagents to systematically analyze the ferret host response to infection are lacking; however, the recent publication of a draft ferret genome has opened the potential for transcriptional analysis of ferret models of disease. In this work, we present comparative analysis of longitudinally sampled blood taken from ferrets and nonhuman primates infected with lethal doses of the Makona variant of Zaire ebolavirus. Strong induction of proinflammatory and prothrombotic signaling programs were present in both ferrets and nonhuman primates, and both transcriptomes were similar to previously published datasets of fatal cases of human Ebola virus infection.

PMID: 30476250 DOI: 10.1093/infdis/jiy455

Keywords: Ebola; Ebola-Makona; Animal models.

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#Survey of #Ebola Viruses in Frugivorous and Insectivorous #Bats in #Guinea, #Cameroon, and the #DRC, 2015–2017 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 24, Number 12—December 2018 / Research

Survey of Ebola Viruses in Frugivorous and Insectivorous Bats in Guinea, Cameroon, and the Democratic Republic of the Congo, 2015–2017

Helene M. De Nys1, Placide Mbala Kingebeni1, Alpha K. Keita1, Christelle Butel, Guillaume Thaurignac, Christian-Julian Villabona-Arenas, Thomas Lemarcis, Mare Geraerts, Nicole Vidal, Amandine Esteban, Mathieu Bourgarel, François Roger, Fabian Leendertz, Ramadan Diallo, Simon-Pierre Ndimbo-Kumugo, Justus Nsio-Mbeta, Nikki Tagg, Lamine Koivogui, Abdoulaye Toure, Eric Delaporte, Steve Ahuka-Mundeke, Jean-Jacques Muyembe Tamfum, Eitel Mpoudi-Ngole, Ahidjo Ayouba2, and Martine Peeters2

Author affiliations: TransVIHMI of Institut de Recherche pour le Développement, Institut National de la Santé et de la Recherche Médicale and University of Montpellier, Montpellier, France (H.M. De Nys, P. Mbala Kingebeni, A.K. Keita, C. Butel, G. Thaurignac, C.-J. Villabona-Arenas, T. Lemarcis, M. Geraerts, N. Vidal, A. Esteban, M. Bourgarel, F. Roger, A. Toure, E. Delaporte, A. Ayouba, M. Peeters); National Institute of Biomedical Research, Kinshasa, Democratic Republic of the Congo (P. Mbala Kingebeni, S.P. Ndimbo-Kumugo, S. Ahuka-Mundeke, J.-J. Muyembe Tamfum); Cliniques Universitaires de Kinshasa, Kinshasa (P. Mbala Kingebeni, S. Ahuka-Mundeke, J.-J. Muyembe Tamfum); Centre de Recherche et de Formation en Infectiologie de Guinée, Conakry, Guinea (A.K. Keita, A. Toure); Robert Koch-Institute, Berlin, Germany (F. Leendertz); Ministère de l’Elevage et des Productions Animales, Conakry (R. Diallo); Direction de Lutte contre la Maladie, Kinshasa (J. Nsio-Mbeta); Royal Zoological Society of Antwerp, Antwerp, Belgium (N. Tagg); Université de Conakry, Conakry (L. Koivogui); Institut National de Sante Publique, Conakry (A. Toure); Institut de Recherches Médicales et d’Études des Plantes Médicinales, Yaoundé, Cameroon (E. Mpoudi-Ngole); Cameroon Institut de Recherche pout le Développement, Yaoundé (E. Mpoudi-Ngole)

 

Abstract

To clarify the role of bats in the ecology of Ebola viruses, we assessed the prevalence of Ebola virus antibodies in a large-scale sample of bats collected during 2015–2017 from countries in Africa that have had previous Ebola outbreaks (Guinea, the Democratic Republic of the Congo) or are at high risk for outbreaks (Cameroon). We analyzed 4,022 blood samples of bats from >12 frugivorous and 27 insectivorous species; 2–37 (0.05%–0.92%) bats were seropositive for Zaire and 0–30 (0%–0.75%) bats for Sudan Ebola viruses. We observed Ebola virus antibodies in 1 insectivorous bat genus and 6 frugivorous bat species. Certain bat species widespread across Africa had serologic evidence of Zaire and Sudan Ebola viruses. No viral RNA was detected in the subset of samples tested (n = 665). Ongoing surveillance of bats and other potential animal reservoirs are required to predict and prepare for future outbreaks.

Keywords: Ebolavirus; Sudan Virus; Ebola Zaire; Bats; Guinea; DRC; Cameroon.

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Rapid confirmation of the #ZEBOV in the #outbreak of the #Equateur province in #DRC: implications for #publichealth interventions (Clin Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Clin Infect Dis. 2018 Jun 29. doi: 10.1093/cid/ciy527. [Epub ahead of print]

Rapid confirmation of the Zaire Ebola Virus in the outbreak of the Equateur province in the Democratic Republic of Congo: implications for public health interventions.

Mbala Kingebeni P1,2,3, Villabona-Arenas CJ3, Vidal N3, Likofata J4, Nsio-Mbeta J5, Makiala-Mandanda S1,2, Mukadi D1,2, Mukadi P1,2, Kumakamba C1,2, Djokolo B5, Ayouba A3, Delaporte E3, Peeters M3, Muyembe Tamfum JJ1,2, Ahuka Mundeke S1,2.

Author information: 1 National Institute of Biomedical Research (INRB), Kinshasa, Democratic Republic of the Congo. 2 Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of Congo. 3 TransVIHMI ; Institut de Recherche pour le Développement, University of Montpellier, INSERM, Montpellier, France. 4 Laboratoire Provinciale, Mbandaka, Democratic Republic of the Congo. 5 Direction Générale de Lutte contre la Maladie (DLM), Kinshasa, Democratic Republic of Congo.

 

Abstract

Ten days after the declaration of the Ebola outbreak in the Equateur Province of the Democratic Republic of Congo, rapid identification of the species Zaire Ebolavirus (EBOV) using partial gene amplification and nanopore sequencing backed up the use of the rVSV-ZEBOV vaccine in the ring vaccination strategy recommended by WHO.

PMID: 29961823 DOI: 10.1093/cid/ciy527

Keywords: Ebola; Ebola-Zaire Virus; DRC.

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