An Outbreak of Ebola Virus Disease in the Lassa Fever Zone

Goba, Augustine; Khan, Sheik Humarr; Fonnie, Mbalu; Fullah, Mohamed; Moigboi, Alex; Kovoma, Alice; Sinnah, Vandi; Yoko, Nancy; Rogers, Hawa; Safai, Siddiki; Momoh, Mambu; Koroma, Veronica J.; Kamara, Fatima K.; Konowu, Edwin; Yillah, Mohamed; French, Issa; Mustapha, Ibraham; Kanneh, Franklyn; Foday, Momoh; McCarthy, Helena; Kallon, Tiangay; Kallon, Mustupha; Naiebu, Jenneh; Sellu, Josephine; Jalloh, Abdul A.; Gbakie, Michael; Kanneh, Lansana; Massaly, James L. B.; Kargbo, David; Kargbo, Brima; Vandi, Mohamed; Gbetuwa, Momoh; Gevao, Sahr M.; Sandi, John Demby; Jalloh, Simbirie; Grant, Donald S.; Blyden, Sylvia O.; Crozier, Ian; Schieffelin, John S.; McLellan, Susan; Jacob, Shevin T.; Boisen, Matthew L.; Hartnett, Jessica N.; Cross, Robert W.; Branco, Luis M.; Andersen, Kristian G.; Yozwiak, Nathan L.; Gire, Stephen K.; Tariyal, Ridhi; Park, Daniel J.; Haislip, Allyson M.; Bishop, Christopher M.; Melnik, Lilia I.; Gallaher, William R.; Wimley, William C.; He, Jing; Shaffer, Jeffrey G.; Sullivan, Brian M.; Grillo, Sonia; Oman, Scott; Garry, Courtney E; Edwards, Donna; McCormick, Stephanie; Elliott, Deborah H.; Rouelle, Julie A.; Kannadka, Chandrika B.; Reyna, Ashley A.; Bradley, Benjamin T.; Yu, Haixia; Yenni, Rachael E.; Hastie, Kathryn M.; Geisbert, Joan B.; Kulakosky, Peter C.; Wilson, Russell B.; Oldstone, Michael B. A.; Pitts, Kelly R.; Henderson, Lee A.; Robinson, James E.; Geisbert, Thomas W.; Saphire, Erica Ollmann; Happi, Christian T.; Asogun, Danny; Sabeti, Pardis C.; Garry, Robert F.

doi:10.1093/infdis/jiw239

Cited by 35 publications

(37 citation statements)

References 45 publications

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“…1A). The Makona EBOV strain was the cause of the 2013-2016 West African outbreak and highly related to the strains present during the first recorded outbreak of EBOV that occurred decades earlier in Zaire, central Africa (23)(24)(25)(26). We rescued 67 additional rscVSVs encoding truncated forms of viral proteins of 36-67 aa for the purpose of defining T cell epitopes in EBOV proteins ( Fig.…”

Section: Results Rvsvs Encoding For Ebov Proteins Can Stimulate Ebov-mentioning

confidence: 99%

Analysis of CD8 ⁺ T cell response during the 2013–2016 Ebola epidemic in West Africa

Sakabe

Sullivan

Hartnett

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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The recent Ebola epidemic exemplified the importance of understanding and controlling emerging infections. Despite the importance of T cells in clearing virus during acute infection, little is known about Ebola-specific CD8 T cell responses. We investigated immune responses of individuals infected with Ebola virus (EBOV) during the 2013-2016 West Africa epidemic in Sierra Leone, where the majority of the >28,000 EBOV disease (EVD) cases occurred. We examined T cell memory responses to seven of the eight Ebola proteins (GP, sGP, NP, VP24, VP30, VP35, and VP40) and associated HLA expression in survivors. Of the 30 subjects included in our analysis, CD8 T cells from 26 survivors responded to at least one EBOV antigen. A minority, 10 of 26 responders (38%), made CD8 T cell responses to the viral GP or sGP. In contrast, 25 of the 26 responders (96%) made response to viral NP, 77% to VP24 (20 of 26), 69% to VP40 (18 of 26), 42% (11 of 26) to VP35, with no response to VP30. Individuals making CD8 T cells to EBOV VP24, VP35, and VP40 also made CD8 T cells to NP, but rarely to GP. We identified 34 CD8 T cell epitopes for Ebola. Our data indicate the immunodominance of the EBOV NP-specific T cell response and suggest that its inclusion in a vaccine along with the EBOV GP would best mimic survivor responses and help boost cell-mediated immunity during vaccination.

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Section: Results Rvsvs Encoding For Ebov Proteins Can Stimulate Ebov-mentioning

confidence: 99%

Analysis of CD8 ⁺ T cell response during the 2013–2016 Ebola epidemic in West Africa

Sakabe

Sullivan

Hartnett

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…The first EBOV introduction from Guinea into another country that resulted in sustained transmission is estimated to have occurred in early April 2014 (Figure 2), when the virus spread to Kailahun District of Sierra Leone 5, 6 . This lineage was first detected in Kailahun at the end of May 2014, from where it spread across the region (Figures 4 & 3).…”

Section: Origin Ignition and Trajectory Of The Epidemicmentioning

confidence: 99%

“…The epidemic is thought to have begun in December 2013 in Guinea, but was not detected and reported until March 2014 3 . Initial efforts to control the outbreak in Guinea were considered to be succeeding 4 , but in early 2014 the virus crossed international borders into neighbouring Liberia (first cases diagnosed in late March) and Sierra Leone (first documented case in late February 5, 6 , first diagnosed cases in May 7 ). EBOV genomes sequenced from three patients in Guinea early in the epidemic 3 demonstrated that the progenitor of the Makona variant originated in Middle Africa and arrived in West Africa within the last 15 years 7, 8 .…”

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confidence: 99%

Virus genomes reveal factors that spread and sustained the Ebola epidemic

Dudas

Carvalho

Bedford

et al. 2017

Nature

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The 2013–2016 epidemic of Ebola virus disease was of unprecedented magnitude, duration and impact. Analysing 1610 Ebola virus genomes, representing over 5% of known cases, we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic ‘gravity’ model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already set the seeds for an international epidemic, rendering these measures ineffective in curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing they were susceptible to significant outbreaks but at lower risk of introductions. Finally, we reveal this large epidemic to be a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help inform interventions in future epidemics.

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“…Thus, current guidelines recommend ribavirin only after high-risk exposures to LASV (5). Given the partial geographic overlap between Ebola virus (EBOV) and LASV in West Africa and similar clinical presentation in early infection stages, it would be advantageous to have a common therapeutic effective against both viruses (6,7).…”

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confidence: 99%

“…Arbidol suppresses LASV GP-mediated cell-cell fusion (CCF). Effector cells were generated by transfecting HEK293T/17 cells with plasmids encoding DSP[1][2][3][4][5][6][7] (the N-terminal split luciferase plasmid) and either LASV GP (A) or WSN influenza HA and NA (B). Target cells were generated by transfecting HEK293T/17 cells with plasmids encoding DSP[8][9][10][11] (the C-terminal split luciferase plasmid) and pmLamp1.…”

mentioning

confidence: 99%

Arbidol and Other Low-Molecular-Weight Drugs That Inhibit Lassa and Ebola Viruses

Hulseberg

Fénéant

Wijs

et al. 2019

J Virol

129

138

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Antiviral therapies that impede virus entry are attractive because they act on the first phase of the infectious cycle. Drugs that target pathways common to multiple viruses are particularly desirable when laboratory-based viral identification may be challenging, e.g., in an outbreak setting. We are interested in identifying drugs that block both Ebola virus (EBOV) and Lassa virus (LASV), two unrelated but highly pathogenic hemorrhagic fever viruses that have caused outbreaks in similar regions in Africa and share features of virus entry: use of cell surface attachment factors, macropinocytosis, endosomal receptors, and low pH to trigger fusion in late endosomes. Toward this goal, we directly compared the potency of eight drugs known to block EBOV entry with their potency as inhibitors of LASV entry. Five drugs (amodiaquine, apilimod, arbidol, niclosamide, and zoniporide) showed roughly equivalent degrees of inhibition of LASV and EBOV glycoprotein (GP)-bearing pseudoviruses; three (clomiphene, sertraline, and toremifene) were more potent against EBOV. We then focused on arbidol, which is licensed abroad as an anti-influenza drug and exhibits activity against a diverse array of clinically relevant viruses. We found that arbidol inhibits infection by authentic LASV, inhibits LASV GP-mediated cell-cell fusion and virus-cell fusion, and, reminiscent of its activity on influenza virus hemagglutinin, stabilizes LASV GP to low-pH exposure. Our findings suggest that arbidol inhibits LASV fusion, which may partly involve blocking conformational changes in LASV GP. We discuss our findings in terms of the potential to develop a drug cocktail that could inhibit both LASV and EBOV. IMPORTANCE Lassa and Ebola viruses continue to cause severe outbreaks in humans, yet there are only limited therapeutic options to treat the deadly hemorrhagic fever diseases they cause. Because of overlapping geographic occurrences and similarities in mode of entry into cells, we seek a practical drug or drug cocktail that could be used to treat infections by both viruses. Toward this goal, we directly compared eight drugs, approved or in clinical testing, for the ability to block entry mediated by the glycoproteins of both viruses. We identified five drugs with approximately equal potencies against both. Among these, we investigated the modes of action of arbidol, a drug licensed abroad to treat influenza infections. We found, as shown for influenza virus, that arbidol blocks fusion mediated by the Lassa virus glycoprotein. Our findings encourage the development of a combination of approved drugs to treat both Lassa and Ebola virus diseases. FIG 2 Comparative effects of arbidol on infection by MLV pseudoviruses bearing LASV or other viral glycoproteins: LASV, LCMV, and Junin GP (A) and LASV GP and influenza virus HA (B). MLV pseudoviruses bearing LASV GP, LCMV GP, Junin GP, or WSN influenza HA and NA were prepared as described in Materials and Methods. BSC-1 cells were pretreated with the indicated concentrations of arbidol and then processed an...

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An Outbreak of Ebola Virus Disease in the Lassa Fever Zone

Cited by 35 publications

References 45 publications

Analysis of CD8 ⁺ T cell response during the 2013–2016 Ebola epidemic in West Africa

Analysis of CD8 ⁺ T cell response during the 2013–2016 Ebola epidemic in West Africa

Virus genomes reveal factors that spread and sustained the Ebola epidemic

Arbidol and Other Low-Molecular-Weight Drugs That Inhibit Lassa and Ebola Viruses

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An Outbreak of Ebola Virus Disease in the Lassa Fever Zone

Cited by 35 publications

References 45 publications

Analysis of CD8 + T cell response during the 2013–2016 Ebola epidemic in West Africa

Analysis of CD8 + T cell response during the 2013–2016 Ebola epidemic in West Africa

Virus genomes reveal factors that spread and sustained the Ebola epidemic

Arbidol and Other Low-Molecular-Weight Drugs That Inhibit Lassa and Ebola Viruses

Contact Info

Product

Resources

About

Analysis of CD8 ⁺ T cell response during the 2013–2016 Ebola epidemic in West Africa

Analysis of CD8 ⁺ T cell response during the 2013–2016 Ebola epidemic in West Africa