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Special Issue "Medical Advances in Viral Hemorrhagic Fever Research"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: 31 May 2019

Special Issue Editors

Guest Editor
Dr. Ian Crozier

NIH/NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), supported by Clinical Monitoring Research Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA
E-Mail
Interests: emerging infectious diseases; viral hemorrhagic fevers; mechanisms of immune privilege and viral persistence; filoviruses; arenaviruses
Guest Editor
Dr. Jens H. Kuhn

NIH/NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), B-8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
Website | E-Mail
Fax: +1 301 631 7389
Interests: arenaviruses; biodefense; bioengagement; BSL-4; filoviruses; henipaviruses; Kyasanur Forest disease virus; nairoviruses; phleboviruses; Omsk hemorrhagic fever virus; simian hemorrhagic fever virus
Guest Editor
Dr. Sheli R. Radoshitzky

United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Website | E-Mail
Interests: molecular virology; emerging infectious diseases; viral hemorrhagic fevers; arenaviruses; filoviruses; alphaviruses

Special Issue Information

Dear Colleagues,

Recent large outbreaks of Ebola and Marburg virus disease (Eastern and Western Africa), Lassa fever (Western Africa), Crimean Congo hemorrhagic fever (Africa, Eastern Europe, Western Asia) and severe fever with thrombocytopenia syndrome (China, Japan, South Korea) have afforded higher-resolution views at human clinical diseases historically referred to as “viral hemorrhagic Fevers.” In addition to updating our understanding of the spectrum and severity of acute disease syndromes, recent encounters have renewed interest in, e.g., the role of pathogen–agnostic care in addition to virus-specific countermeasures, clinical sequelae after infection, and viral persistence potentially associated with inflammatory syndromes or risk of transmission and outbreak re-ignition. Although there are no FDA-approved medical countermeasures against these viral agents, increased funding, interest, and novel technologies have accelerated research and understanding of many medical aspects of these and other, more neglected (e.g., Alkhurma, Chapare, Guanarito, Kyasanur Forest disease, Lujo, Omsk hemorrhagic fever, Sabiá viruses), viral hemorrhagic fever-causing pathogens. New clinical data and at-bedside approached, advanced genomics and proteomics tools, CRISPR-Cas9 screens, and novel off-label or IND-level vaccine and therapeutics platforms have all contributed (or have the potential) to expand our knowledge of disease course, pathogenesis, and molecular epidemiology, as well as to the development of better diagnostics and medical countermeasures. The present Special Issue covers a wide range of topics focusing on human clinical disease related to such “Medical Advances in Viral Hemorrhagic Fever Research".

Dr. Ian Crozier
Dr. Jens H. Kuhn
Dr. Sheli R. Radoshitzky
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • arenaviruses
  • filoviruses
  • flaviviruses
  • bunyaviruses
  • clinical presentation
  • epidemiology/outbreak response
  • pathology/pathogenesis
  • medical countermeasures
  • diagnostics

Published Papers (6 papers)

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Research

Open AccessArticle Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses
Viruses 2019, 11(3), 293; https://doi.org/10.3390/v11030293
Received: 20 February 2019 / Revised: 14 March 2019 / Accepted: 20 March 2019 / Published: 23 March 2019
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Abstract
Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related Old-World mammarenaviruses. LASV causes severe hemorrhagic fever with high mortality in humans, whereas no case of MOPV infection has been reported. Comparing MOPV and LASV is a powerful strategy to unravel pathogenic [...] Read more.
Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related Old-World mammarenaviruses. LASV causes severe hemorrhagic fever with high mortality in humans, whereas no case of MOPV infection has been reported. Comparing MOPV and LASV is a powerful strategy to unravel pathogenic mechanisms that occur during the course of pathogenic arenavirus infection. We used a yeast two-hybrid approach to identify cell partners of MOPV and LASV Z matrix protein in which two autophagy adaptors were identified, NDP52 and TAX1BP1. Autophagy has emerged as an important cellular defense mechanism against viral infections but its role during arenavirus infection has not been shown. Here, we demonstrate that autophagy is transiently induced by MOPV, but not LASV, in infected cells two days after infection. Impairment of the early steps of autophagy significantly decreased the production of MOPV and LASV infectious particles, whereas a blockade of the degradative steps impaired only MOPV infectious particle production. Our study provides insights into the role played by autophagy during MOPV and LASV infection and suggests that this process could partially explain their different pathogenicity. Full article
(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)
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Open AccessArticle Non-Pathogenic Mopeia Virus Induces More Robust Activation of Plasmacytoid Dendritic Cells than Lassa Virus
Viruses 2019, 11(3), 287; https://doi.org/10.3390/v11030287
Received: 28 January 2019 / Revised: 4 March 2019 / Accepted: 18 March 2019 / Published: 21 March 2019
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Abstract
Lassa virus (LASV) causes a viral haemorrhagic fever in humans and is a major public health concern in West Africa. An efficient immune response to LASV appears to rely on type I interferon (IFN-I) production and T-cell activation. We evaluated the response of [...] Read more.
Lassa virus (LASV) causes a viral haemorrhagic fever in humans and is a major public health concern in West Africa. An efficient immune response to LASV appears to rely on type I interferon (IFN-I) production and T-cell activation. We evaluated the response of plasmacytoid dendritic cells (pDC) to LASV, as they are an important and early source of IFN-I. We compared the response of primary human pDCs to LASV and Mopeia virus (MOPV), which is very closely related to LASV, but non-pathogenic. We showed that pDCs are not productively infected by either MOPV or LASV, but produce IFN-I. However, the activation of pDCs was more robust in response to MOPV than LASV. In vivo, pDC activation may support the control of viral replication through IFN-I production, but also improve the induction of a global immune response. Therefore, pDC activation could play a role in the control of LASV infection. Full article
(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)
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Open AccessArticle Bovine Herpesvirus Type 4 (BoHV-4) Vector Delivering Nucleocapsid Protein of Crimean-Congo Hemorrhagic Fever Virus Induces Comparable Protective Immunity against Lethal Challenge in IFNα/β/γR−/− Mice Models
Viruses 2019, 11(3), 237; https://doi.org/10.3390/v11030237
Received: 29 January 2019 / Revised: 4 March 2019 / Accepted: 5 March 2019 / Published: 9 March 2019
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Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of a tick-borne infection with a significant mortality rate of up to 40% in endemic areas, with evidence of geographical expansion. Due to a lack of effective therapeutics and control measures, the development of [...] Read more.
Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of a tick-borne infection with a significant mortality rate of up to 40% in endemic areas, with evidence of geographical expansion. Due to a lack of effective therapeutics and control measures, the development of a protective CCHFV vaccine remains a crucial public health task. This paper describes, for the first time, a Bovine herpesvirus type 4 (BoHV-4)-based viral vector (BoHV4-∆TK-CCHFV-N) and its immunogenicity in BALB/c and protection potential in IFNα/β/γR−/− mice models in comparison with two routinely used vaccine platforms, namely, Adenovirus type 5 and a DNA vector (pCDNA3.1 myc/His A), expressing the same antigen. All vaccine constructs successfully elicited significantly elevated cytokine levels and specific antibody responses in immunized BALB/c and IFNα/β/γR−/− mice. However, despite highly specific antibody responses in both animal models, the antibodies produced were unable to neutralize the virus in vitro. In the challenge experiment, only the BoHV4-∆TK-CCHFV-N and Ad5-N constructs produced 100% protection against lethal doses of the CCHFV Ank-2 strain in IFNα/β/γR−/− mice. The delivery platforms could not be compared due to similar protection rates in IFNα/β/γR−/− mice. However, during the challenge experiment in the T cell and passive antibody transfer assay, BoHV4-∆TK-CCHFV-N was dominant, with a protection rate of 75% compared to others. In conclusion, vector-based CCHFV N protein expression constitutes an effective approach for vaccine development and BoHV-4 emerged as a strong alternative to previously used viral vectors. Full article
(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)
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Open AccessArticle Priorities, Barriers, and Facilitators towards International Guidelines for the Delivery of Supportive Clinical Care during an Ebola Outbreak: A Cross-Sectional Survey
Viruses 2019, 11(2), 194; https://doi.org/10.3390/v11020194
Received: 29 January 2019 / Revised: 18 February 2019 / Accepted: 20 February 2019 / Published: 23 February 2019
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Abstract
During the Ebola outbreak, mortality reduction was attributed to multiple improvements in supportive care delivered in Ebola treatment units (ETUs). We aimed to identify high-priority supportive care measures, as well as perceived barriers and facilitators to their implementation, for patients with Ebola Virus [...] Read more.
During the Ebola outbreak, mortality reduction was attributed to multiple improvements in supportive care delivered in Ebola treatment units (ETUs). We aimed to identify high-priority supportive care measures, as well as perceived barriers and facilitators to their implementation, for patients with Ebola Virus Disease (EVD). We conducted a cross-sectional survey of key stakeholders involved in the response to the 2014–2016 West African EVD outbreak. Out of 57 email invitations, 44 responses were received, and 29 respondents completed the survey. The respondents listed insufficient numbers of health workers (23/29, 79%), improper tools for the documentation of clinical data (n = 22/28, 79%), insufficient material resources (n = 22/29, 76%), and unadapted personal protective equipment (n = 20/28, 71%) as the main barriers to the provision of supportive care in ETUs. Facilitators to the provision of supportive care included team camaraderie (n in agreement = 25/28, 89%), ability to speak the local language (22/28, 79%), and having treatment protocols in place (22/28, 79%). This survey highlights a consensus across various stakeholders involved in the response to the 2014–2016 EVD outbreak on a limited number of high-priority supportive care interventions for clinical practice guidelines. Identified barriers and facilitators further inform the application of guidelines. Full article
(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)
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Open AccessArticle Co-Delivery Effect of CD24 on the Immunogenicity and Lethal Challenge Protection of a DNA Vector Expressing Nucleocapsid Protein of Crimean Congo Hemorrhagic Fever Virus
Viruses 2019, 11(1), 75; https://doi.org/10.3390/v11010075
Received: 26 November 2018 / Revised: 10 January 2019 / Accepted: 12 January 2019 / Published: 17 January 2019
Cited by 1 | PDF Full-text (5061 KB) | HTML Full-text | XML Full-text
Abstract
Crimean Congo hemorrhagic fever virus (CCHFV) is the causative agent of a globally-spread tick-borne zoonotic infection, with an eminent risk of fatal human disease. The imminent public health threat posed by the disseminated virus activity and lack of an approved therapeutic make CCHFV [...] Read more.
Crimean Congo hemorrhagic fever virus (CCHFV) is the causative agent of a globally-spread tick-borne zoonotic infection, with an eminent risk of fatal human disease. The imminent public health threat posed by the disseminated virus activity and lack of an approved therapeutic make CCHFV an urgent target for vaccine development. We described the construction of a DNA vector expressing a nucleocapsid protein (N) of CCHFV (pV-N13), and investigated its potential to stimulate the cytokine and total/specific antibody responses in BALB/c and a challenge experiment in IFNAR−/− mice. Because of a lack of sufficient antibody stimulation towards the N protein, we have selected cluster of differentiation 24 (CD24) protein as a potential adjuvant, which has a proliferative effect on B and T cells. Overall, our N expressing construct, when administered solely or in combination with the pCD24 vector, elicited significant cellular and humoral responses in BALB/c, despite variations in the particular cytokines and total antibodies. However, the stimulated antibodies produced as a result of the N protein expression have shown no neutralizing ability in the virus neutralization assay. Furthermore, the challenge experiments revealed the protection potential of the N expressing construct in an IFNAR −/− mice model. The cytokine analysis in the IFNAR−/− mice showed an elevation in the IL-6 and TNF-alpha levels. In conclusion, we have shown that targeting the S segment of CCHFV can be considered for a practical way to develop a vaccine against this virus, because of its ability to induce an immune response, which leads to protection in the challenge assays in the interferon (IFN)-gamma defective mice models. Moreover, CD24 has a prominent immunologic effect when it co-delivers with a suitable foreign gene expressing vector. Full article
(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)
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Open AccessArticle Phylodynamic Analysis of Ebola Virus Disease Transmission in Sierra Leone
Viruses 2019, 11(1), 71; https://doi.org/10.3390/v11010071
Received: 27 December 2018 / Revised: 11 January 2019 / Accepted: 14 January 2019 / Published: 16 January 2019
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Abstract
We generated genome sequences from 218 cases of Ebola virus disease (EVD) in Sierra Leone (SLE) during 2014–2015 to complement available datasets, particularly by including cases from a period of low sequence coverage during peak transmission of Ebola virus (EBOV) in the highly-affected [...] Read more.
We generated genome sequences from 218 cases of Ebola virus disease (EVD) in Sierra Leone (SLE) during 2014–2015 to complement available datasets, particularly by including cases from a period of low sequence coverage during peak transmission of Ebola virus (EBOV) in the highly-affected Western Area division of SLE. The combined dataset was utilized to produce phylogenetic and phylodynamic inferences, to study sink–source dynamics and virus dispersal from highly-populated transmission hotspots. We identified four districts in SLE where EBOV was introduced and transmission occurred without onward exportation to other districts. We also identified six districts that substantially contributed to the dispersal of the virus and prolonged the EVD outbreak: five of these served as major hubs, with lots of movement in and out, and one acted primarily as a source, exporting the virus to other areas of the country. Positive correlations between case numbers, inter-district transition events, and district population sizes reaffirm that population size was a driver of EBOV transmission dynamics in SLE. The data presented here confirm the role of urban hubs in virus dispersal and of a delayed laboratory response in the expansion and perpetuation of the EVD outbreak in SLE. Full article
(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)
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