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Developing VHH-based tools to study Ebolavirus Infection By Jason V. M. H. Nguyen B.S., Biochemistry and Molecular Biology University of California, Santa Cruz, 2012 Submitted to the Microbiology Graduate Program in partial fulfillment of the requirements for the degree of Doctor of Philosophy At the Massachusetts Institute of Technology June 2019 2019 Massachusetts Institute of Technology. All rights reserved. Signature redacted Signature of Author...... .................................................................... V Y' Jason V. M. H. Nguyen Microbiology Graduate Program May 13, 2019 Signature redacted Certified by.............. ................................................................... Hidde L. Ploegh Senior Investigator Boston Children's Hospital It Signature redacted Accepted by....... ......................................................................... Jacquin C. Niles Associate Professor of Biological Engineering Chair of Microbiology Program MASSACHUSETTS INSTITUTE OF TECHNOLOGY JUN 2 12019 1 LIBRARIES ARCHIVES 2 Developing VHH-based tools to study Ebolavirus Infection By Jason V. M. H. Nguyen Submitted to the Microbiology Graduate Program on May 13th, 2019 in partial fulfillment of the requirements for the degree of Doctor of Philosophy ABSTRACT Variable domains of camelid-derived heavy chain-only antibodies, or VHHs, have emerged as a unique antigen binding moiety that holds promise in its versatility and utilization as a tool to study biological questions. This thesis focuses on two aspects on developing tools to study infectious disease, specifically Ebolavirus entry. In Chapter 1, I provide an overview about antibodies and how antibodies have transformed the biomedical field and how single domain antibody fragments, or VHHs, have entered this arena. I will also touch upon how VHHs have been used in various fields and certain aspects that remain underexplored. Chapter 2 focuses on the utilization of VHHs to study Ebolavirus entry using VHHs that were isolated from alpacas. -
MARBURG HEMORRHAGIC FEVER (Marburg HF)
MARBURG HEMORRHAGIC FEVER (Marburg HF) REPORTING INFORMATION • Class A: Report immediately via telephone the case or suspected case and/or a positive laboratory result to the local public health department where the patient resides. If patient residence is unknown, report immediately via telephone to the local public health department in which the reporting health care provider or laboratory is located. Local health departments should report immediately via telephone the case or suspected case and/or a positive laboratory result to the Ohio Department of Health (ODH). • Reporting Form(s) and/or Mechanism: o Immediately via telephone. o For local health departments, cases should also be entered into the Ohio Disease Reporting System (ODRS) within 24 hours of the initial telephone report to the ODH. • Key fields for ODRS reporting include: import status (whether the infection was travel-associated or Ohio-acquired), date of illness onset, and all the fields in the Epidemiology module. AGENT Marburg hemorrhagic fever is a rare, severe type of hemorrhagic fever which affects both humans and non-human primates. Caused by a genetically unique zoonotic RNA virus of the family Filoviridae, its recognition led to the creation of this virus family. The five species of Ebola virus are the only other known members of the family Filoviridae. Marburg virus was first recognized in 1967, when outbreaks of hemorrhagic fever occurred simultaneously in laboratories in Marburg and Frankfurt, Germany and in Belgrade, Yugoslavia (now Serbia). A total of 31 people became ill, including laboratory workers as well as several medical personnel and family members who had cared for them. -
A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures
viruses Communication A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures Ryan P. Bennett 1,† , Courtney L. Finch 2,† , Elena N. Postnikova 2 , Ryan A. Stewart 1, Yingyun Cai 2 , Shuiqing Yu 2 , Janie Liang 2, Julie Dyall 2 , Jason D. Salter 1 , Harold C. Smith 1,* and Jens H. Kuhn 2,* 1 OyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USA; [email protected] (R.P.B.); [email protected] (R.A.S.); [email protected] (J.D.S.) 2 NIH/NIAID/DCR/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA; courtney.fi[email protected] (C.L.F.); [email protected] (E.N.P.); [email protected] (Y.C.); [email protected] (S.Y.); [email protected] (J.L.); [email protected] (J.D.) * Correspondence: [email protected] (H.C.S.); [email protected] (J.H.K.); Tel.: +1-585-697-4351 (H.C.S.); +1-301-631-7245 (J.H.K.) † These authors contributed equally to this work. Abstract: Filoviruses, such as Ebola virus and Marburg virus, are of significant human health concern. From 2013 to 2016, Ebola virus caused 11,323 fatalities in Western Africa. Since 2018, two Ebola virus disease outbreaks in the Democratic Republic of the Congo resulted in 2354 fatalities. Although there is progress in medical countermeasure (MCM) development (in particular, vaccines and antibody- based therapeutics), the need for efficacious small-molecule therapeutics remains unmet. Here we describe a novel high-throughput screening assay to identify inhibitors of Ebola virus VP40 matrix protein association with viral particle assembly sites on the interior of the host cell plasma membrane. -
MARBURG VIRUS [African Hemorrhagic Fever, Green Or Vervet Monkey Disease]
MARBURG VIRUS [African Hemorrhagic Fever, Green or Vervet Monkey Disease] SPECIES: Nonhuman primates, especially african green monkeys & macaques AGENT: Agent is classified as a Filovirus. It is an RNA virus, superficially resembling rhabdoviruses but has bizarre branching and filamentous or tubular forms shared with no other known virus group on EM. The only other member of this class of viruses is ebola virus. RESERVOIR AND INCIDENCE: An acute highly fatal disease first described in Marburg, Germany in 1967. Brought to Marburg in a shipment of infected African Green Monkeys from Uganda. 31 people were affected and 7 died in 1967. Exposure to tissue and blood from African Green monkeys (Cercopithecus aethiops) or secondary contact with infected humans led to the disease. No disease occurred in people who handled only intact animals or those who wore gloves and protective clothing when handling tissues. A second outbreak was reported in Africa in 1975 involving three people with no verified contact with monkeys. Third and fourth outbreaks in Kenya 1980 and 1987. Natural reservoir is unknown. Monkeys thought to be accidental hosts along with man. Antibodies have been found in African Green monkeys, baboons, and chimpanzees. 100% fatal in experimentally infected African Green Monkeys, Rhesus, squirrel monkeys, guinea pigs, and hamsters. TRANSMISSION: Direct contact with infected blood or tissues or close contact with infected patients. Virus has also been found in semen, saliva, and urine. DISEASE IN NONHUMAN PRIMATES: No clinical signs occur in green monkeys, but the disease is usually fatal after experimental infection of other primate species. Leukopenia and petechial hemorrhages throughout the body of experimentally infected monkeys, sometimes with GI hemorrhages. -
2019 Icar Program & Abstracts Book
Hosted by the International Society for Antiviral Research (ISAR) ND International Conference 32on Antiviral Research (ICAR) Baltimore MARYLAND PROGRAM and USA Hyatt Regency BALTIMORE ABSTRACTS May 12-15 2019 ND TABLE OF International Conference CONTENTS 32on Antiviral Research (ICAR) Daily Schedule . .3 Organization . 4 Contributors . 5 Keynotes & Networking . 6 Schedule at a Glance . 7 ISAR Awardees . 10 The 2019 Chu Family Foundation Scholarship Awardees . 15 Speaker Biographies . 17 Program Schedule . .25 Posters . 37 Abstracts . 53 Author Index . 130 PROGRAM and ABSTRACTS of the 32nd International Conference on Antiviral Research (ICAR) 2 ND DAILY International Conference SCHEDULE 32on Antiviral Research (ICAR) SUNDAY, MAY 12, 2019 › Women in Science Roundtable › Welcome and Keynote Lectures › Antonín Holý Memorial Award Lecture › Influenza Symposium › Opening Reception MONDAY, MAY 13, 2019 › Women in Science Award Lecture › Emerging Virus Symposium › Short Presentations 1 › Poster Session 1 › Retrovirus Symposium › ISAR Award of Excellence Presentation › PechaKucha Event with Introduction of First Time Attendees TUESDAY, MAY 14, 2019 › What’s New in Antiviral Research 1 › Short Presentations 2 & 3 › ISAR Award for Outstanding Contributions to the Society Presentation › Career Development Panel › William Prusoff Young Investigator Award Lecture › Medicinal Chemistry Symposium › Poster Session 2 › Networking Reception WEDNESDAY, MAY 15, 2019 › Gertrude Elion Memorial Award Lecture › What’s New in Antiviral Research 2 › Shotgun Oral -
How Severe and Prevalent Are Ebola and Marburg Viruses?
Nyakarahuka et al. BMC Infectious Diseases (2016) 16:708 DOI 10.1186/s12879-016-2045-6 RESEARCHARTICLE Open Access How severe and prevalent are Ebola and Marburg viruses? A systematic review and meta-analysis of the case fatality rates and seroprevalence Luke Nyakarahuka1,2,5* , Clovice Kankya2, Randi Krontveit3, Benjamin Mayer4, Frank N. Mwiine2, Julius Lutwama5 and Eystein Skjerve1 Abstract Background: Ebola and Marburg virus diseases are said to occur at a low prevalence, but are very severe diseases with high lethalities. The fatality rates reported in different outbreaks ranged from 24–100%. In addition, sero-surveys conducted have shown different seropositivity for both Ebola and Marburg viruses. We aimed to use a meta-analysis approach to estimate the case fatality and seroprevalence rates of these filoviruses, providing vital information for epidemic response and preparedness in countries affected by these diseases. Methods: Published literature was retrieved through a search of databases. Articles were included if they reported number of deaths, cases, and seropositivity. We further cross-referenced with ministries of health, WHO and CDC databases. The effect size was proportion represented by case fatality rate (CFR) and seroprevalence. Analysis was done using the metaprop command in STATA. Results: The weighted average CFR of Ebola virus disease was estimated to be 65.0% [95% CI (54.0–76.0%), I2 = 97.98%] whereas that of Marburg virus disease was 53.8% (26.5–80.0%, I2 = 88.6%). The overall seroprevalence of Ebola virus was 8.0% (5.0%–11.0%, I2 = 98.7%), whereas that for Marburg virus was 1.2% (0.5–2.0%, I2 = 94.8%). -
Development of an Antibody Cocktail for Treatment of Sudan Virus Infection
Development of an antibody cocktail for treatment of Sudan virus infection Andrew S. Herberta,b, Jeffery W. Froudea,1, Ramon A. Ortiza, Ana I. Kuehnea, Danielle E. Doroskya, Russell R. Bakkena, Samantha E. Zaka,b, Nicole M. Josleyna,b, Konstantin Musiychukc, R. Mark Jonesc, Brian Greenc, Stephen J. Streatfieldc, Anna Z. Wecd,2, Natasha Bohorovae, Ognian Bohorove, Do H. Kime, Michael H. Paulye, Jesus Velascoe, Kevin J. Whaleye, Spencer W. Stoniera,b,3, Zachary A. Bornholdte, Kartik Chandrand, Larry Zeitline, Darryl Sampeyf, Vidadi Yusibovc,4, and John M. Dyea,5 aVirology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702; bThe Geneva Foundation, Tacoma, WA 98402; cFraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711; dDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; eMapp Biopharmaceutical, Inc., San Diego, CA 92121; and fBioFactura, Inc., Frederick, MD 21701 Edited by Y. Kawaoka, University of Wisconsin–Madison/University of Tokyo, Madison, WI, and approved December 30, 2019 (received for review August 28, 2019) Antibody-based therapies are a promising treatment option for antibody-based immunotherapies. Subsequently, several indepen- managing ebolavirus infections. Several Ebola virus (EBOV)-specific dent groups reported the postexposure efficacy of monoclonal and, more recently, pan-ebolavirus antibody cocktails have been antibody (mAb)-based immunotherapies against EVD in ma- described. Here, we report the development and assessment of a caques when administered as mixtures of two or more mAbs (14–17). Sudan virus (SUDV)-specific antibody cocktail. We produced a panel These landmark studies demonstrated that combination mAb- of SUDV glycoprotein (GP)-specific human chimeric monoclonal based immunotherapies are a viable treatment option for EVD antibodies (mAbs) using both plant and mammalian expression and spurred therapeutic antibody development for filoviruses. -
Understanding Ebola
Understanding Ebola With the arrival of Ebola in the United States, it's very easy to develop fears that the outbreak that has occurred in Africa will suddenly take shape in your state and local community. It's important to remember that unless you come in direct contact with someone who is infected with the disease, you and your family will remain safe. State and government agencies have been making preparations to address isolated cases of infection and stop the spread of the disease as soon as it has been positively identified. Every day, the Centers of Disease Control and Prevention (CDC) is monitoring developments, testing for suspected cases and safeguarding our lives with updates on events and the distribution of educational resources. Learning more about Ebola and understanding how it's contracted and spread will help you put aside irrational concerns and control any fears you might have about Ebola severely impacting your life. Use the resources below to help keep yourself calm and focused during this unfortunate time. Ebola Hemorrhagic Fever Ebola hemorrhagic fever (Ebola HF) is one of numerous Viral Hemorrhagic Fevers. It is a severe, often fatal disease in humans and nonhuman primates (such as monkeys, gorillas, and chimpanzees). Ebola HF is caused by infection with a virus of the family Filoviridae, genus Ebolavirus. When infection occurs, symptoms usually begin abruptly. The first Ebolavirus species was discovered in 1976 in what is now the Democratic Republic of the Congo near the Ebola River. Since then, outbreaks have appeared sporadically. There are five identified subspecies of Ebolavirus. -
Taï Forest Virus Does Not Cause Lethal Disease in Ferrets
microorganisms Article Taï Forest Virus Does Not Cause Lethal Disease in Ferrets Zachary Schiffman 1,2,† , Feihu Yan 3,†, Shihua He 2, Kevin Tierney 2, Wenjun Zhu 2 , Karla Emeterio 1,2, Huajun Zhang 1, Logan Banadyga 2,* and Xiangguo Qiu 2 1 Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 0J9, Canada; [email protected] (Z.S.); [email protected] (K.E.); [email protected] (H.Z.) 2 Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; [email protected] (S.H.); [email protected] (K.T.); [email protected] (W.Z.); [email protected] (X.Q.) 3 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China; [email protected] * Correspondence: [email protected] † These authors contributed equally. Abstract: Filoviruses are zoonotic, negative-sense RNA viruses, most of which are capable of causing severe disease in humans and nonhuman primates, often with high case fatality rates. Among these viruses, those belonging to the Ebolavirus genus—particularly Ebola virus, Sudan virus, and Bundibugyo virus—represent some of the most pathogenic to humans. Taï Forest virus (TAFV) is thought to be among the least pathogenic ebolaviruses; however, only a single non-fatal case has been documented in humans, in 1994. With the recent success of the ferret as a lethal model for a number of ebolaviruses, we set out to evaluate its suitability as a model for TAFV. Our results demonstrate that, unlike other ebolaviruses, TAFV infection in ferrets does not result in lethal disease. -
Principais Métodos De Diagnóstico E Tratamento Da Doença Causada Pelo Vírus Ebola
Revista Ciencia & Inovação - FAM - V.5, N.1 - JUN - 2020 PRINCIPAIS MÉTODOS DE DIAGNÓSTICO E TRATAMENTO DA DOENÇA CAUSADA PELO VÍRUS EBOLA Jaqueline Pereira Fernandes Patricia Ucelli Simioni Graduada de Biomedicina, Faculdade de Americana (FAM) Bióloga, mestre e doutora em Imunologia, [email protected] Faculdade de Americana, [email protected] Monna Abdel Latif Elaine Cristina Berro Graduada de Biomedicina, Faculdade de Americana (FAM) Engenheira Ambiental, especialista em Microbiologia, [email protected] Faculdade de americana (FAM), [email protected] Leila Ugrinovich Bióloga, mestre e doutora em Microbiologia, Faculdade de Americana, [email protected] RESUMO ABSTRACT Ebola é uma doença grave causada pelo Ebola vírus, Ebola is a serious disease caused by the Ebola virus da família Filoviridae, que apresenta altos índices of the Filoviridae family has high mortality rates. Bat, de mortalidade. Animais como morcego, chimpanzé chimpanzee and monkey may be hosts of the virus. e macaco podem ser hospedeiros do vírus. O The diagnosis is only made by specialized laboratories, diagnóstico adequado é feito apenas em laboratórios based on the isolation of viral RNA. However, especializados, a partir do isolamento do RNA viral. current diagnostic methodologies include real-time Entretanto, metodologias atuais de diagnóstico incluem polymerase chain reaction (PRC) and assessment reação de polimerase em cadeia (PRC) em tempo real of immunoglobulins (Ig) M and G Currently available e avaliação de imunoglobulinas (Ig) M e G As terapias therapies are palliative. New therapies are already disponíveis atualmente são paliativas. Novas terapias já being tested in humans and promise advances in the estão em fase de testes em seres humanos e prometem treatment of the disease, although their safety and avanços no tratamento da doença, embora ainda não effectiveness have not yet been proven. -
Experience of Ebola Virus Disease in the Province of North Kivu and Ituri (DR Congo) and the Importance of Early Diagnosis
Open Access Library Journal 2020, Volume 7, e6135 ISSN Online: 2333-9721 ISSN Print: 2333-9705 Problem of the Management of Haemorrhagic Fevers: Experience of Ebola Virus Disease in the Province of North Kivu and Ituri (DR Congo) and the Importance of Early Diagnosis Criss Koba Mjumbe1,2*, Isabelle Kasongo Omba1, Benjamain Kabyla Ilunga1, Oscar Luboya Nuymbi1 1Department of Public Health, Faculty of Medicine of Lubumbashi, Lubumbashi, Democratic Republic of the Congo 2Department of Internal Medicine, Saint Joseph Polyclinic/GCM, Lubumbashi, Democratic Republic of the Congo How to cite this paper: Koba Mjumbe, C., Abstract Kasongo Omba, I., Kabyla Ilunga, B. and Luboya Nuymbi, O. (2020) Problem of the Ebola is a serious, often fatal disease with a fatality rate of up to 90%. The Management of Haemorrhagic Fevers: short-term objective of this letter to the listeners is to make known the signs Experience of Ebola Virus Disease in the of the Ebola virus to the population and to promote the early diagnosis in our Province of North Kivu and Ituri (DR Congo) and the Importance of Early environment. We applied an observation of the cases of the Ebola epidemic in Diagnosis. Open Access Library Journal, 7: our environment. It is not always possible to quickly identify patients with e6135. Ebola virus disease. For this reason, it is important that health workers apply https://doi.org/10.4236/oalib.1106135 the usual precautions to all patients, regardless of diagnosis, in any profes- Received: February 3, 2020 sional practice and at any time. With the support of the Congolese govern- Accepted: March 3, 2020 ment and several other organizations, the Congolese government is expected Published: March 6, 2020 to launch a program of mass awareness and vaccination against the Ebola vi- rus. -
Ebola Virus Disease Outbreak in North Kivu and Ituri Provinces, Democratic Republic of the Congo – Second Update
RAPID RISK ASSESSMENT Ebola virus disease outbreak in North Kivu and Ituri Provinces, Democratic Republic of the Congo – second update 21 December 2018 Main conclusions As of 16 December 2018, the Ministry of Health of the Democratic Republic of Congo (DRC) has reported 539 Ebola virus disease (EVD) cases, including 48 probable and 491 confirmed cases. This epidemic in the provinces of North Kivu and Ituri is the largest outbreak of EVD recorded in DRC and the second largest worldwide. A total of 315 deaths occurred during the reporting period. As of 16 December 2018, 52 healthcare workers (50 confirmed and two probable) have been reported among the confirmed cases, and of these 17 have died. As of 10 December 2018, the overall case fatality rate was 58%. Since mid-October, an average of around 30 new cases has been reported every week, with 14 health zones reporting confirmed cases in the past 21 days. This trend shows that the outbreak is continuing across geographically dispersed areas. Although the transmission intensity has decreased in Beni, the outbreak is continuing in Butembo city, and new clusters are emerging in the surrounding health zones. A geographical extension of the outbreak (within the country and to neighbouring countries) cannot be excluded as it is unlikely that it will be controlled in the near future. Despite significant achievements, the implementation of response measures remains problematic because of the prolonged humanitarian crisis in North Kivu province, the unstable security situation arising from a complex armed conflict and the mistrust of affected communities in response activities.