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Article ; Online: Nipah Virus Outbreaks: Still Small but Extremely Lethal.

Spiropoulou, Christina F

2018 Volume 219, Issue 12, Page(s) 1855–1857

MeSH term(s)	Disease Outbreaks ; Henipavirus Infections ; Humans ; India ; Nipah Virus
Language	English
Publishing date	2018-10-26
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiy611
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Article ; Online: Twenty Years of Nipah Virus Research: Where Do We Go From Here?

Gurley, Emily S / Spiropoulou, Christina F / de Wit, Emmie

The Journal of infectious diseases

2020 Volume 221, Issue Suppl 4, Page(s) S359–S362

MeSH term(s)	Animals ; Disease Outbreaks ; Henipavirus Infections/epidemiology ; Henipavirus Infections/history ; Henipavirus Infections/virology ; History, 21st Century ; Humans ; India/epidemiology ; Nipah Virus/classification ; Nipah Virus/isolation & purification ; Philippines/epidemiology
Language	English
Publishing date	2020-05-11
Publishing country	United States
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Intramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiaa078
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Article ; Online: The use of mice lacking type I or both type I and type II interferon responses in research on hemorrhagic fever viruses. Part 2: Vaccine efficacy studies.

Zivcec, Marko / Spiropoulou, Christina F / Spengler, Jessica R

Antiviral research

2020 Volume 174, Page(s) 104702

Abstract: For more than 20 years, researchers have used laboratory mice lacking type I or both type I and II interferon (IFN) responses to study high-containment viruses that cause hemorrhagic fevers (HF) in humans. With the exception of Rift Valley fever virus, ... ...

Abstract	For more than 20 years, researchers have used laboratory mice lacking type I or both type I and II interferon (IFN) responses to study high-containment viruses that cause hemorrhagic fevers (HF) in humans. With the exception of Rift Valley fever virus, agents that cause viral HF in humans, such as Ebola and Lassa virus, do not cause disease in mature immunocompetent mice. In contrast, IFN-deficient mice typically develop severe or fatal disease when inoculated with these agents. The sensitivity of IFN-deficient mice to disease has led to their widespread use in biocontainment laboratories to assess the efficacy of novel vaccines against HF viruses, often without considering whether adaptive immune responses in IFN-deficient mice accurately mirror those in immunocompetent humans. Failure to recognize these questions may lead to inappropriate expectations of the predictive value of mouse experiments. In two invited articles, we investigate these questions. The present article reviews the use of IFN-deficient mice for assessing novel vaccines against HF viruses, including Ebola, Lassa, Crimean-Congo hemorrhagic fever and Rift Valley fever viruses. A companion paper examines the general question of how the lack of IFN signaling may affect adaptive immune responses and the outcome of vaccine studies in mice.
MeSH term(s)	Animals ; Antibodies, Viral/blood ; Disease Models, Animal ; Hemorrhagic Fevers, Viral/immunology ; Hemorrhagic Fevers, Viral/prevention & control ; Interferon Type I/deficiency ; Interferon-gamma/deficiency ; Mice ; Viral Vaccines/immunology
Chemical Substances	Antibodies, Viral ; Interferon Type I ; Viral Vaccines ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2020-01-22
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2019.104702
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Article ; Online: Development of a novel minigenome and recombinant VSV expressing Seoul hantavirus glycoprotein-based assays to identify anti-hantavirus therapeutics.

Shrivastava-Ranjan, Punya / Jain, Shilpi / Chatterjee, Payel / Montgomery, Joel M / Flint, Mike / Albariño, César / Spiropoulou, Christina F

Antiviral research

2023 Volume 214, Page(s) 105619

Abstract: Seoul virus (SEOV) is an emerging global health threat that can cause hemorrhagic fever with renal syndrome (HFRS), which results in case fatality rates of ∼2%. There are no approved treatments for SEOV infections. We developed a cell-based assay system ... ...

Abstract	Seoul virus (SEOV) is an emerging global health threat that can cause hemorrhagic fever with renal syndrome (HFRS), which results in case fatality rates of ∼2%. There are no approved treatments for SEOV infections. We developed a cell-based assay system to identify potential antiviral compounds for SEOV and generated additional assays to characterize the mode of action of any promising antivirals. To test if candidate antivirals targeted SEOV glycoprotein-mediated entry, we developed a recombinant reporter vesicular stomatitis virus expressing SEOV glycoproteins. To facilitate the identification of candidate antiviral compounds targeting viral transcription/replication, we successfully generated the first reported minigenome system for SEOV. This SEOV minigenome (SEOV-MG) screening assay will also serve as a prototype assay for discovery of small molecules inhibiting replication of other hantaviruses, including Andes and Sin Nombre viruses. Ours is a proof-of-concept study in which we tested several compounds previously reported to have activity against other negative-strand RNA viruses using our newly developed hantavirus antiviral screening systems. These systems can be used under lower biocontainment conditions than those needed for infectious viruses, and identified several compounds with robust anti-SEOV activity. Our findings have important implications for the development of anti-hantavirus therapeutics.
MeSH term(s)	Humans ; Orthohantavirus/genetics ; Seoul virus/genetics ; Seoul ; Hantavirus Infections ; Hemorrhagic Fever with Renal Syndrome ; Recombinant Proteins ; Glycoproteins ; Vesiculovirus/genetics
Chemical Substances	Recombinant Proteins ; Glycoproteins
Language	English
Publishing date	2023-05-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2023.105619
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Article ; Online: Filoviruses: Scientific Gaps and Prototype Pathogen Recommendation.

Dupuy, Lesley C / Spiropoulou, Christina F / Towner, Jonathan S / Spengler, Jessica R / Sullivan, Nancy J / Montgomery, Joel M

The Journal of infectious diseases

2023 Volume 228, Issue Suppl 6, Page(s) S446–S459

Abstract: Viruses in the family Filoviridae, including the commonly known Ebola (EBOV) and Marburg (MARV) viruses, can cause severe hemorrhagic fever in humans and nonhuman primates. Sporadic outbreaks of filovirus disease occur in sub-Saharan Africa with reported ...

Abstract	Viruses in the family Filoviridae, including the commonly known Ebola (EBOV) and Marburg (MARV) viruses, can cause severe hemorrhagic fever in humans and nonhuman primates. Sporadic outbreaks of filovirus disease occur in sub-Saharan Africa with reported case fatality rates ranging from 25% to 90%. The high mortality and increasing frequency and magnitude of recent outbreaks along with the increased potential for spread from rural to urban areas highlight the importance of pandemic preparedness for these viruses. Despite their designation as high-priority pathogens, numerous scientific gaps exist in critical areas. In this review, these gaps and an assessment of potential prototype pathogen candidates are presented for this important virus family.
MeSH term(s)	Animals ; Humans ; Filoviridae ; Ebolavirus ; Hemorrhagic Fever, Ebola/epidemiology ; Hemorrhagic Fever, Ebola/prevention & control ; Marburgvirus ; Disease Outbreaks
Language	English
Publishing date	2023-10-17
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad362
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Article ; Online: Development of reverse genetic tools to study Chapare and Machupo viruses.

Jain, Shilpi / Shrivastava-Ranjan, Punya / Flint, Mike / Montgomery, Joel M / Spiropoulou, Christina F / Albariño, César G

Virology

2023 Volume 588, Page(s) 109888

Abstract: Arenaviruses are highly pathogenic viruses that pose a serious public health threat. Chapare virus (CHAV) and Machupo virus (MACV), two New World arenaviruses, cause hemorrhagic fevers with case fatality rates of up to 45%. Research on therapeutic drug ... ...

Abstract	Arenaviruses are highly pathogenic viruses that pose a serious public health threat. Chapare virus (CHAV) and Machupo virus (MACV), two New World arenaviruses, cause hemorrhagic fevers with case fatality rates of up to 45%. Research on therapeutic drug targets and vaccines for these viruses is limited because biosafety level 4 containment is required for handling them. In this study, we developed reverse genetics systems, including minigenomes and recombinant viruses, that will facilitate the study of these pathogens. The minigenome system is based on the S segment of CHAV or MACV genomes expressing the fluorescent reporter gene ZsGreen (ZsG). We also generated recombinant CHAV and MACV with and without the ZsG reporter gene. As a proof-of-concept study, we used both minigenomes and recombinant viruses to test the inhibitory effects of previously reported antiviral compounds. The new reverse genetics system described here will facilitate future therapeutic studies for these two life-threatening arenaviruses.
MeSH term(s)	Arenaviruses, New World ; Reverse Genetics
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2023.109888
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Article ; Online: Crimean-Congo hemorrhagic fever and expansion from endemic regions.

Spengler, Jessica R / Bergeron, Éric / Spiropoulou, Christina F

Current opinion in virology

2019 Volume 34, Page(s) 70–78

Abstract: Crimean-Congo hemorrhagic fever (CCHF) is a virus-mediated hemorrhagic disease that occurs over a wide geographic region. In recent years, a variety of active and passive surveillance networks have improved our knowledge of areas with existing ... ...

Abstract	Crimean-Congo hemorrhagic fever (CCHF) is a virus-mediated hemorrhagic disease that occurs over a wide geographic region. In recent years, a variety of active and passive surveillance networks have improved our knowledge of areas with existing circulation of Crimean-Congo hemorrhagic fever virus (CCHFV), the etiologic agent of CCHF. These investigations aid in better defining the distribution of the virus. Expansion of a virus into new areas can occur through a variety of means, including introduction of infected humans, vectors, or animals. Here, these potential contributors to expansion of CCHFV into neighboring countries and geographically distant locations are reviewed, and the likelihood and possible implications of these events, based on known characteristics of the virus and its natural maintenance and transmission cycles are explored. Furthermore, this report discusses limitations in the currently described distribution of CCHFV, and the challenges in assessing viral circulation identified in a new region as geographic expansion of the virus.
MeSH term(s)	Animals ; Endemic Diseases ; Epidemiological Monitoring ; Geography ; Hemorrhagic Fever Virus, Crimean-Congo/genetics ; Hemorrhagic Fever Virus, Crimean-Congo/pathogenicity ; Hemorrhagic Fever, Crimean/epidemiology ; Hemorrhagic Fever, Crimean/transmission ; Humans ; Livestock/virology ; Public Health ; Ticks/virology
Language	English
Publishing date	2019-01-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	2611378-8
ISSN	1879-6265 ; 1879-6257
ISSN (online)	1879-6265
ISSN	1879-6257
DOI	10.1016/j.coviro.2018.12.002
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Article ; Online: Evaluation of two inoculation routes of an adenovirus-mediated viral protein inhibitor in a Crimean-Congo hemorrhagic fever mouse model.

Scholte, Florine E M / Spengler, Jessica R / Welch, Stephen R / Harmon, Jessica R / Coleman-McCray, JoAnn D / Davies, Katherine A / Pegan, Scott D / Montgomery, Joel M / Spiropoulou, Christina F / Bergeron, Éric

Virus research

2024 , Page(s) 199398

Abstract: Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne nairovirus with a wide geographic spread that can cause severe and lethal disease. No specific medical countermeasures are approved to combat this illness. The CCHFV L protein contains an ... ...

Abstract	Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne nairovirus with a wide geographic spread that can cause severe and lethal disease. No specific medical countermeasures are approved to combat this illness. The CCHFV L protein contains an ovarian tumor OTU domain with a cysteine protease thought to modulate cellular immune responses by removing ubiquitin and ISG15 post-translational modifications from host and viral proteins. Viral deubiquitinases like CCHFV OTU are attractive drug targets, as blocking their activity may enhance cellular immune responses to infection, and potentially inhibit viral replication itself. We previously demonstrated that the engineered ubiquitin variant CC4 is a potent inhibitor of CCHFV replication in vitro. A major challenge of the therapeutic use of small protein inhibitors such as CC4 is their requirement for intracellular delivery, e.g., by viral vectors. In this study, we examined the feasibility of in vivo CC4 delivery by a replication-deficient recombinant adenovirus (Ad-CC4) in a lethal CCHFV mouse model. Since the liver is a primary target of CCHFV infection, we aimed to optimize delivery to this organ by comparing intravenous (tail vein) and intraperitoneal injection of Ad-CC4. While tail vein injection is a traditional route for adenovirus delivery, in our hands intraperitoneal injection resulted in higher and more widespread levels of adenovirus genome in tissues, including, as intended, the liver. However, despite promising in vitro results, neither route of in vivo CC4 treatment resulted in protection from a lethal CCHFV infection.
Language	English
Publishing date	2024-05-14
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2024.199398
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Article ; Online: Exploring inactivation of SARS-CoV-2, MERS-CoV, Ebola, Lassa, and Nipah viruses on N95 and KN95 respirator material using photoactivated methylene blue to enable reuse.

Scholte, Florine E M / Kabra, Kareem B / Tritsch, Sarah R / Montgomery, Joel M / Spiropoulou, Christina F / Mores, Christopher N / Harcourt, Brian H

American journal of infection control

2022 Volume 50, Issue 8, Page(s) 863–870

Abstract: Background: The COVID-19 pandemic resulted in a worldwide shortage of N95 respirators, prompting the development of decontamination methods to enable limited reuse. Countries lacking reliable supply chains would also benefit from the ability to safely ... ...

Abstract	Background: The COVID-19 pandemic resulted in a worldwide shortage of N95 respirators, prompting the development of decontamination methods to enable limited reuse. Countries lacking reliable supply chains would also benefit from the ability to safely reuse PPE. Methylene blue (MB) is a light-activated dye with demonstrated antimicrobial activity used to sterilize blood plasma. Decontamination of respirators using photoactivated MB requires no specialized equipment, making it attractive for use in the field during outbreaks. Methods: We examined decontamination of N95 and KN95 respirators using photoactivated MB and 3 variants of SARS-CoV-2, the virus that causes COVID-19; and 4 World Health Organization priority pathogens: Ebola virus, Middle East respiratory syndrome coronavirus, Nipah virus, and Lassa virus. Virus inactivation by pretreating respirator material was also tested. Results: Photoactivated MB inactivated all tested viruses on respirator material, albeit with varying efficiency. Virus applied to respirator material pre-treated with MB was also inactivated, thus MB pretreatment may potentially protect respirator wearers from virus exposure in real-time. Conclusions: These results demonstrate that photoactivated MB represents a cost-effective, rapid, and widely deployable method to decontaminate N95 respirators for reuse during supply shortages.
MeSH term(s)	COVID-19/prevention & control ; Decontamination/methods ; Equipment Reuse ; Hemorrhagic Fever, Ebola/prevention & control ; Humans ; Methylene Blue/pharmacology ; Middle East Respiratory Syndrome Coronavirus ; N95 Respirators ; Nipah Virus ; Pandemics/prevention & control ; SARS-CoV-2 ; Ventilators, Mechanical
Chemical Substances	Methylene Blue (T42P99266K)
Language	English
Publishing date	2022-07-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	392362-9
ISSN	1527-3296 ; 0196-6553
ISSN (online)	1527-3296
ISSN	0196-6553
DOI	10.1016/j.ajic.2022.02.016
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Article ; Online: Rift Valley fever virus vaccination induces long-lived, antigen-specific human T cell responses.

Harmon, Jessica R / Barbeau, Dominique J / Nichol, Stuart T / Spiropoulou, Christina F / McElroy, Anita K

NPJ vaccines

2020 Volume 5, Issue 1, Page(s) 17

Abstract: Rift Valley fever virus (RVFV) is a zoonotic arbovirus of clinical significance in both livestock and humans. A formalin-inactivated virus preparation was initially developed for human use and tested in laboratory workers in the 1960s. Vaccination ... ...

Abstract	Rift Valley fever virus (RVFV) is a zoonotic arbovirus of clinical significance in both livestock and humans. A formalin-inactivated virus preparation was initially developed for human use and tested in laboratory workers in the 1960s. Vaccination resulted in generation of neutralizing antibody titers in most recipients, but neutralization titers waned over time, necessitating frequent booster doses. In this study, T cell-based immune responses to the formalin-inactivated vaccine were examined in a cohort of seven individuals who received between 1 and 6 doses of the vaccine. RVFV-specific T cell responses were detectable up to 24 years post vaccination. Peripheral blood mononuclear cells from this cohort of individuals were used to map out the viral epitopes targeted by T cells in humans. These data provide tools for assessing human RVFV-specific T cell responses and are thus a valuable resource for future human RVFV vaccine efforts.
Language	English
Publishing date	2020-02-28
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-020-0166-9
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