E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Topical Collection "Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research"

A topical collection in Viruses (ISSN 1999-4915). This collection belongs to the section "Animal Viruses".

Editor

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

Topical Collection Information

Dear Colleagues,

Filoviruses (cuevaviruses, ebolaviruses, and marburgviruses) are exotic high-consequence human and animal pathogens that must be handled in maximum (biosafety level 4) containment. This topic collection aims at providing an opportunity for filovirologists and other experts to publish not only general articles or reviews on any filovirus research topic, but also to distribute announcements of committee discussions or decisions, meeting reports, facility or method descriptions, and personal viewpoints or hypotheses. The goal of this open access topic collection is to further communication among interested scientists with particular emphasis on providing citable information on thoughts or ideas generally “known in the community” that are yet unpublished.

Sincerely,
Jens H. Kuhn

Keywords

  • Ebola
  • Ebola virus
  • EBOV
  • ebolavirus
  • filovirid
  • Filoviridae
  • filovirus
  • Marburg virus
  • marburgvirus
  • Bundibugyo virus
  • BDBV
  • Sudan virus
  • SUDV
  • Taï Forest virus
  • TAFV
  • Reston virus
  • RESTV
  • Bundibugyo ebolavirus
  • Zaire ebolavirus
  • Sudan ebolavirus
  • Reston ebolavirus
  • Taï Forest ebolavirus
  • Marburg marburgvirus
  • MARV
  • Ravn virus
  • mononegavirus
  • mononegavirad
  • Mononegavirales
  • RAVV
  • BSL-4
  • BSL4
  • biosafety level 4
  • maximum containment
  • bioterrorism
  • biological terrorism
  • biowarfare
  • biological warfare
  • bioweapon
  • biological weapon
  • medical countermeasure
  • viral hemorrhagic fever
  • viral haemorrhagic fever
  • cuevavirus
  • Lloviu virus
  • LLOV
  • Lloviu cuevavirus

Related Special Issue

Published Papers (33 papers)

2017

Jump to: 2016, 2015, 2014

Open AccessLetter Implementation of Objective PASC-Derived Taxon Demarcation Criteria for Official Classification of Filoviruses
Viruses 2017, 9(5), 106; doi:10.3390/v9050106
Received: 26 April 2017 / Revised: 26 April 2017 / Accepted: 2 May 2017 / Published: 11 May 2017
PDF Full-text (837 KB) | HTML Full-text | XML Full-text
Abstract
The mononegaviral family Filoviridae has eight members assigned to three genera and seven species. Until now, genus and species demarcation were based on arbitrarily chosen filovirus genome sequence divergence values (≈50% for genera, ≈30% for species) and arbitrarily chosen phenotypic virus or virion
[...] Read more.
The mononegaviral family Filoviridae has eight members assigned to three genera and seven species. Until now, genus and species demarcation were based on arbitrarily chosen filovirus genome sequence divergence values (≈50% for genera, ≈30% for species) and arbitrarily chosen phenotypic virus or virion characteristics. Here we report filovirus genome sequence-based taxon demarcation criteria using the publicly accessible PAirwise Sequencing Comparison (PASC) tool of the US National Center for Biotechnology Information (Bethesda, MD, USA). Comparison of all available filovirus genomes in GenBank using PASC revealed optimal genus demarcation at the 55–58% sequence diversity threshold range for genera and at the 23–36% sequence diversity threshold range for species. Because these thresholds do not change the current official filovirus classification, these values are now implemented as filovirus taxon demarcation criteria that may solely be used for filovirus classification in case additional data are absent. A near-complete, coding-complete, or complete filovirus genome sequence will now be required to allow official classification of any novel “filovirus.” Classification of filoviruses into existing taxa or determining the need for novel taxa is now straightforward and could even become automated using a presented algorithm/flowchart rooted in RefSeq (type) sequences. Full article
Figures

2016

Jump to: 2017, 2015, 2014

Open AccessArticle Antiviral Screening of Multiple Compounds against Ebola Virus
Viruses 2016, 8(11), 277; doi:10.3390/v8110277
Received: 19 September 2016 / Revised: 19 October 2016 / Accepted: 19 October 2016 / Published: 27 October 2016
Cited by 1 | PDF Full-text (602 KB) | HTML Full-text | XML Full-text
Abstract
In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using
[...] Read more.
In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease. Full article
Figures

Figure 1

Open AccessArticle Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications
Viruses 2016, 8(8), 206; doi:10.3390/v8080206
Received: 4 May 2016 / Revised: 8 July 2016 / Accepted: 19 July 2016 / Published: 2 August 2016
Cited by 5 | PDF Full-text (2974 KB) | HTML Full-text | XML Full-text
Abstract
The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is,
[...] Read more.
The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist. Here we compared the ability of clomiphene and its isomers to inhibit EBOV using viral-like particle (VLP) entry and transcription/replication-competent VLP (trVLP) assays. Clomiphene and its isomers inhibited the entry and infection of VLPs and trVLPs with similar potencies. This was demonstrated with VLPs bearing the glycoproteins from three filoviruses (EBOV Mayinga, EBOV Makona, and Marburg virus) and in two cell lines (293T/17 and Vero E6). Visual problems have been noted in EBOV survivors, and viral RNA has been isolated from semen up to nine months post-infection. Since the clomiphene isomers accumulate in these affected tissues, clomiphene or one of its isomers warrants consideration as an anti-EBOV agent, for example, to potentially help ameliorate symptoms in EBOV survivors. Full article
Figures

Figure 1

Open AccessArticle Effectiveness of Four Disinfectants against Ebola Virus on Different Materials
Viruses 2016, 8(7), 185; doi:10.3390/v8070185
Received: 25 April 2016 / Revised: 20 June 2016 / Accepted: 24 June 2016 / Published: 7 July 2016
Cited by 1 | PDF Full-text (869 KB) | HTML Full-text | XML Full-text
Abstract
The West Africa Ebola virus (EBOV) outbreak has highlighted the need for effective disinfectants capable of reducing viral load in a range of sample types, equipment and settings. Although chlorine-based products are widely used, they can also be damaging to equipment or apparatus
[...] Read more.
The West Africa Ebola virus (EBOV) outbreak has highlighted the need for effective disinfectants capable of reducing viral load in a range of sample types, equipment and settings. Although chlorine-based products are widely used, they can also be damaging to equipment or apparatus that needs continuous use such as aircraft use for transportation of infected people. Two aircraft cleaning solutions were assessed alongside two common laboratory disinfectants in a contact kill assay with EBOV on two aircraft relevant materials representative of a porous and non-porous surface. A decimal log reduction of viral titre of 4 is required for a disinfectant to be deemed effective and two of the disinfectants fulfilled this criteria under the conditions tested. One product, Ardrox 6092, was found to perform similarly to sodium hypochlorite, but as it does not have the corrosive properties of sodium hypochlorite, it could be an alternative disinfectant solution to be used for decontamination of EBOV on sensitive apparatus. Full article
Open AccessReview Aerosol Transmission of Filoviruses
Viruses 2016, 8(5), 148; doi:10.3390/v8050148
Received: 24 December 2015 / Revised: 18 May 2016 / Accepted: 20 May 2016 / Published: 23 May 2016
Cited by 2 | PDF Full-text (255 KB) | HTML Full-text | XML Full-text
Abstract
Filoviruses have become a worldwide public health concern because of their potential for introductions into non-endemic countries through international travel and the international transport of infected animals or animal products. Since it was first identified in 1976, in the Democratic Republic of Congo
[...] Read more.
Filoviruses have become a worldwide public health concern because of their potential for introductions into non-endemic countries through international travel and the international transport of infected animals or animal products. Since it was first identified in 1976, in the Democratic Republic of Congo (formerly Zaire) and Sudan, the 2013–2015 western African Ebola virus disease (EVD) outbreak is the largest, both by number of cases and geographical extension, and deadliest, recorded so far in medical history. The source of ebolaviruses for human index case(s) in most outbreaks is presumptively associated with handling of bush meat or contact with fruit bats. Transmission among humans occurs easily when a person comes in contact with contaminated body fluids of patients, but our understanding of other transmission routes is still fragmentary. This review deals with the controversial issue of aerosol transmission of filoviruses. Full article
Open AccessCorrection Correction: Reynard, O.; et al. Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication. Viruses 2015, 7, 6233‒6240
Viruses 2016, 8(5), 137; doi:10.3390/v8050137
Received: 9 May 2016 / Accepted: 9 May 2016 / Published: 18 May 2016
PDF Full-text (448 KB) | HTML Full-text | XML Full-text
Abstract The Viruses Editorial Office wishes to notify its readers of corrections in [1].[...] Full article
Open AccessArticle Validation of the Filovirus Plaque Assay for Use in Preclinical Studies
Viruses 2016, 8(4), 113; doi:10.3390/v8040113
Received: 19 January 2016 / Revised: 21 March 2016 / Accepted: 28 March 2016 / Published: 21 April 2016
Cited by 1 | PDF Full-text (2201 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A plaque assay for quantitating filoviruses in virus stocks, prepared viral challenge inocula and samples from research animals has recently been fully characterized and standardized for use across multiple institutions performing Biosafety Level 4 (BSL-4) studies. After standardization studies were completed, Good Laboratory
[...] Read more.
A plaque assay for quantitating filoviruses in virus stocks, prepared viral challenge inocula and samples from research animals has recently been fully characterized and standardized for use across multiple institutions performing Biosafety Level 4 (BSL-4) studies. After standardization studies were completed, Good Laboratory Practices (GLP)-compliant plaque assay method validation studies to demonstrate suitability for reliable and reproducible measurement of the Marburg Virus Angola (MARV) variant and Ebola Virus Kikwit (EBOV) variant commenced at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). The validation parameters tested included accuracy, precision, linearity, robustness, stability of the virus stocks and system suitability. The MARV and EBOV assays were confirmed to be accurate to ±0.5 log10 PFU/mL. Repeatability precision, intermediate precision and reproducibility precision were sufficient to return viral titers with a coefficient of variation (%CV) of ≤30%, deemed acceptable variation for a cell-based bioassay. Intraclass correlation statistical techniques for the evaluation of the assay’s precision when the same plaques were quantitated by two analysts returned values passing the acceptance criteria, indicating high agreement between analysts. The assay was shown to be accurate and specific when run on Nonhuman Primates (NHP) serum and plasma samples diluted in plaque assay medium, with negligible matrix effects. Virus stocks demonstrated stability for freeze-thaw cycles typical of normal usage during assay retests. The results demonstrated that the EBOV and MARV plaque assays are accurate, precise and robust for filovirus titration in samples associated with the performance of GLP animal model studies. Full article
Open AccessArticle Virus-Like Particle Vaccination Protects Nonhuman Primates from Lethal Aerosol Exposure with Marburgvirus (VLP Vaccination Protects Macaques against Aerosol Challenges)
Viruses 2016, 8(4), 94; doi:10.3390/v8040094
Received: 2 December 2015 / Revised: 23 March 2016 / Accepted: 24 March 2016 / Published: 8 April 2016
Cited by 1 | PDF Full-text (2334 KB) | HTML Full-text | XML Full-text
Abstract
Marburg virus (MARV) was the first filovirus to be identified following an outbreak of viral hemorrhagic fever disease in Marburg, Germany in 1967. Due to several factors inherent to filoviruses, they are considered a potential bioweapon that could be disseminated via an aerosol
[...] Read more.
Marburg virus (MARV) was the first filovirus to be identified following an outbreak of viral hemorrhagic fever disease in Marburg, Germany in 1967. Due to several factors inherent to filoviruses, they are considered a potential bioweapon that could be disseminated via an aerosol route. Previous studies demonstrated that MARV virus-like particles (VLPs) containing the glycoprotein (GP), matrix protein VP40 and nucleoprotein (NP) generated using a baculovirus/insect cell expression system could protect macaques from subcutaneous (SQ) challenge with multiple species of marburgviruses. In the current study, the protective efficacy of the MARV VLPs in conjunction with two different adjuvants: QS-21, a saponin derivative, and poly I:C against homologous aerosol challenge was assessed in cynomolgus macaques. Antibody responses against the GP antigen were equivalent in all groups receiving MARV VLPs irrespective of the adjuvant; adjuvant only-vaccinated macaques did not demonstrate appreciable antibody responses. All macaques were subsequently challenged with lethal doses of MARV via aerosol or SQ as a positive control. All MARV VLP-vaccinated macaques survived either aerosol or SQ challenge while animals administered adjuvant only exhibited clinical signs and lesions consistent with MARV disease and were euthanized after meeting the predetermined criteria. Therefore, MARV VLPs induce IgG antibodies recognizing MARV GP and VP40 and protect cynomolgus macaques from an otherwise lethal aerosol exposure with MARV. Full article
Open AccessArticle Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques
Viruses 2016, 8(4), 87; doi:10.3390/v8040087
Received: 1 December 2015 / Revised: 20 February 2016 / Accepted: 20 February 2016 / Published: 30 March 2016
PDF Full-text (3537 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine
[...] Read more.
Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule—a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis. Full article
Open AccessEditorial Testing New Hypotheses Regarding Ebolavirus Reservoirs
Viruses 2016, 8(2), 30; doi:10.3390/v8020030
Received: 13 November 2015 / Revised: 15 January 2016 / Accepted: 18 January 2016 / Published: 26 January 2016
Cited by 4 | PDF Full-text (162 KB) | HTML Full-text | XML Full-text
Abstract
Despite a relatively long search for the origin of ebolaviruses, their reservoirs remain elusive. Researchers might have to consider testing alternative hypotheses about how these viruses persist and emerge to advance ebolavirus research. This article aims to encourage researchers to bring forward such
[...] Read more.
Despite a relatively long search for the origin of ebolaviruses, their reservoirs remain elusive. Researchers might have to consider testing alternative hypotheses about how these viruses persist and emerge to advance ebolavirus research. This article aims to encourage researchers to bring forward such hypotheses, to discuss them scientifically and to open alternative research avenues regarding the origin and ecology of ebolaviruses. Full article
Open AccessArticle Experimental Inoculation of Egyptian Fruit Bats (Rousettus aegyptiacus) with Ebola Virus
Viruses 2016, 8(2), 29; doi:10.3390/v8020029
Received: 27 September 2015 / Revised: 30 December 2015 / Accepted: 6 January 2016 / Published: 22 January 2016
Cited by 6 | PDF Full-text (644 KB) | HTML Full-text | XML Full-text
Abstract
Colonized Egyptian fruit bats (Rousettus aegyptiacus), originating in South Africa, were inoculated subcutaneously with Ebola virus (EBOV). No overt signs of morbidity, mortality, or gross lesions were noted. Bats seroconverted by Day 10–16 post inoculation (p.i.), with the highest mean anti-EBOV
[...] Read more.
Colonized Egyptian fruit bats (Rousettus aegyptiacus), originating in South Africa, were inoculated subcutaneously with Ebola virus (EBOV). No overt signs of morbidity, mortality, or gross lesions were noted. Bats seroconverted by Day 10–16 post inoculation (p.i.), with the highest mean anti-EBOV IgG level on Day 28 p.i. EBOV RNA was detected in blood from one bat. In 16 other tissues tested, viral RNA distribution was limited and at very low levels. No seroconversion could be demonstrated in any of the control bats up to 28 days after in-contact exposure to subcutaneously-inoculated bats. The control bats were subsequently inoculated intraperitoneally, and intramuscularly with the same dose of EBOV. No mortality, morbidity or gross pathology was observed in these bats. Kinetics of immune response was similar to that in subcutaneously-inoculated bats. Viral RNA was more widely disseminated to multiple tissues and detectable in a higher proportion of individuals, but consistently at very low levels. Irrespective of the route of inoculation, no virus was isolated from tissues which tested positive for EBOV RNA. Viral RNA was not detected in oral, nasal, ocular, vaginal, penile and rectal swabs from any of the experimental groups. Full article

2015

Jump to: 2017, 2016, 2014

Open AccessArticle Ebola Virus Infections in Nonhuman Primates Are Temporally Influenced by Glycoprotein Poly-U Editing Site Populations in the Exposure Material
Viruses 2015, 7(12), 6739-6754; doi:10.3390/v7122969
Received: 20 July 2015 / Revised: 3 December 2015 / Accepted: 7 December 2015 / Published: 19 December 2015
Cited by 5 | PDF Full-text (1481 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recent experimentation with the variants of the Ebola virus that differ in the glycoprotein’s poly-uridine site, which dictates the form of glycoprotein produced through a transcriptional stutter, has resulted in questions regarding the pathogenicity and lethality of the stocks used to develop products
[...] Read more.
Recent experimentation with the variants of the Ebola virus that differ in the glycoprotein’s poly-uridine site, which dictates the form of glycoprotein produced through a transcriptional stutter, has resulted in questions regarding the pathogenicity and lethality of the stocks used to develop products currently undergoing human clinical trials to combat the disease. In order to address these concerns and prevent the delay of these critical research programs, we designed an experiment that permitted us to intramuscularly challenge statistically significant numbers of naïve and vaccinated cynomolgus macaques with either a 7U or 8U variant of the Ebola virus, Kikwit isolate. In naïve animals, no difference in survivorship was observed; however, there was a significant delay in the disease course between the two groups. Significant differences were also observed in time-of-fever, serum chemistry, and hematology. In vaccinated animals, there was no statistical difference in survivorship between either challenge groups, with two succumbing in the 7U group compared to 1 in the 8U challenge group. In summary, survivorship was not affected, but the Ebola virus disease course in nonhuman primates is temporally influenced by glycoprotein poly-U editing site populations. Full article
Figures

Open AccessBrief Report Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication
Viruses 2015, 7(12), 6233-6240; doi:10.3390/v7122934
Received: 9 July 2015 / Revised: 16 November 2015 / Accepted: 18 November 2015 / Published: 1 December 2015
Cited by 3 | PDF Full-text (917 KB) | HTML Full-text | XML Full-text
Abstract
The current outbreak of Ebola virus (EBOV) in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to
[...] Read more.
The current outbreak of Ebola virus (EBOV) in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to interfere with EBOV replication. Among them, the cytidine analogue β-d-N4-hydroxycytidine (NHC) demonstrated potent inhibitory activities against EBOV replication and spread at non-cytotoxic concentrations. Thus, NHC constitutes an interesting candidate for the development of a suitable drug treatment against EBOV. Full article
Open AccessArticle Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism
Viruses 2015, 7(10), 5587-5602; doi:10.3390/v7102888
Received: 9 July 2015 / Revised: 6 October 2015 / Accepted: 14 October 2015 / Published: 26 October 2015
Cited by 3 | PDF Full-text (5537 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including Ebola virus, from infected cells. As with many viruses targeted by host factors, Ebola virus employs a tetherin antagonist, the viral glycoprotein (EboGP), to counteract restriction and promote
[...] Read more.
Tetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including Ebola virus, from infected cells. As with many viruses targeted by host factors, Ebola virus employs a tetherin antagonist, the viral glycoprotein (EboGP), to counteract restriction and promote virus release. Unlike other tetherin antagonists such as HIV-1 Vpu or KSHV K5, the features within EboGP needed to overcome tetherin are not well characterized. Here, we describe sequences within the EboGP ectodomain and membrane spanning domain (msd) as necessary to relieve tetherin restriction of viral particle budding. Fusing the EboGP msd to a normally secreted form of the glycoprotein effectively promotes Ebola virus particle release. Cellular protein or lipid anchors could not substitute for the EboGP msd. The requirement for the EboGP msd was not specific for filovirus budding, as similar results were seen with HIV particles. Furthermore trafficking of chimeric proteins to budding sites did not correlate with an ability to counter tetherin. Additionally, we find that a glycoprotein construct, which mimics the cathepsin-activated species by proteolytic removal of the EboGP glycan cap and mucin domains, is unable to counteract tetherin. Combining these results suggests an important role for the EboGP glycan cap and msd in tetherin antagonism. Full article
Open AccessReview The Role of Cytokines and Chemokines in Filovirus Infection
Viruses 2015, 7(10), 5489-5507; doi:10.3390/v7102892
Received: 1 September 2015 / Revised: 9 October 2015 / Accepted: 14 October 2015 / Published: 23 October 2015
Cited by 4 | PDF Full-text (3974 KB) | HTML Full-text | XML Full-text
Abstract
Ebola- and marburgviruses are highly pathogenic filoviruses and causative agents of viral hemorrhagic fever. Filovirus disease is characterized by a dysregulated immune response, severe organ damage, and coagulation abnormalities. This includes modulation of cytokines, signaling mediators that regulate various components of the immune
[...] Read more.
Ebola- and marburgviruses are highly pathogenic filoviruses and causative agents of viral hemorrhagic fever. Filovirus disease is characterized by a dysregulated immune response, severe organ damage, and coagulation abnormalities. This includes modulation of cytokines, signaling mediators that regulate various components of the immune system as well as other biological processes. Here we examine the role of cytokines in filovirus infection, with an emphasis on understanding how these molecules affect development of the antiviral immune response and influence pathology. These proteins may present targets for immune modulation by therapeutic agents and vaccines in an effort to boost the natural immune response to infection and/or reduce immunopathology. Full article
Figures

Open AccessReview Filoviruses: One of These Things is (not) Like the Other
Viruses 2015, 7(10), 5172-5190; doi:10.3390/v7102867
Received: 6 August 2015 / Revised: 15 September 2015 / Accepted: 16 September 2015 / Published: 29 September 2015
Cited by 7 | PDF Full-text (256 KB) | HTML Full-text | XML Full-text
Abstract
The family Filoviridae contains several of the most deadly pathogens known to date and the current Ebola virus disease (EVD) outbreak in Western Africa, due to Ebola virus (EBOV) infection, highlights the need for active and broad research into filovirus pathogenesis. However, in
[...] Read more.
The family Filoviridae contains several of the most deadly pathogens known to date and the current Ebola virus disease (EVD) outbreak in Western Africa, due to Ebola virus (EBOV) infection, highlights the need for active and broad research into filovirus pathogenesis. However, in comparison, the seven other known filovirus family members are significantly understudied. Many of these, including Marburgviruses and Ebolaviruses other than EBOV, are also highly virulent and fully capable of causing widespread epidemics. This review places the focus on these non-EBOV filoviruses, including known immunological and pathological data. The available animal models, research tools and currently available therapeutics will also be discussed along with an emphasis in the large number of current gaps in knowledge of these less highlighted filoviruses. It is evident that much research is yet to be done in order to bring the non-EBOV filovirus field to the forefront of current research and, importantly, to the development of more effective vaccines and therapeutics to combat potential future outbreaks. Full article
Open AccessEssay Learning from Ebola Virus: How to Prevent Future Epidemics
Viruses 2015, 7(7), 3789-3797; doi:10.3390/v7072797
Received: 27 May 2015 / Revised: 25 June 2015 / Accepted: 26 June 2015 / Published: 9 July 2015
Cited by 3 | PDF Full-text (99 KB) | HTML Full-text | XML Full-text
Abstract
The recent Ebola virus disease (EVD) epidemic in Guinea, Liberia and Sierra Leone demonstrated that the World Health Organization (WHO) is incapable to control outbreaks of infectious diseases in less developed regions of the world. This essay analyses the causes for the failure
[...] Read more.
The recent Ebola virus disease (EVD) epidemic in Guinea, Liberia and Sierra Leone demonstrated that the World Health Organization (WHO) is incapable to control outbreaks of infectious diseases in less developed regions of the world. This essay analyses the causes for the failure of the international response and proposes four measures to improve resilience, early detection and response to future outbreaks of infectious diseases. Full article
Open AccessArticle Experimental Inoculation of Egyptian Rousette Bats (Rousettus aegyptiacus) with Viruses of the Ebolavirus and Marburgvirus Genera
Viruses 2015, 7(7), 3420-3442; doi:10.3390/v7072779
Received: 14 May 2015 / Revised: 12 June 2015 / Accepted: 16 June 2015 / Published: 25 June 2015
Cited by 21 | PDF Full-text (1568 KB) | HTML Full-text | XML Full-text
Abstract
The Egyptian rousette bat (Rousettus aegyptiacus) is a natural reservoir for marburgviruses and a consistent source of virus spillover to humans. Cumulative evidence suggests various bat species may also transmit ebolaviruses. We investigated the susceptibility of Egyptian rousettes to each of
[...] Read more.
The Egyptian rousette bat (Rousettus aegyptiacus) is a natural reservoir for marburgviruses and a consistent source of virus spillover to humans. Cumulative evidence suggests various bat species may also transmit ebolaviruses. We investigated the susceptibility of Egyptian rousettes to each of the five known ebolaviruses (Sudan, Ebola, Bundibugyo, Taï Forest, and Reston), and compared findings with Marburg virus. In a pilot study, groups of four juvenile bats were inoculated with one of the ebolaviruses or Marburg virus. In ebolavirus groups, viral RNA tissue distribution was limited, and no bat became viremic. Sudan viral RNA was slightly more widespread, spurring a second, 15-day Sudan virus serial euthanasia study. Low levels of Sudan viral RNA disseminated to multiple tissues at early time points, but there was no viremia or shedding. In contrast, Marburg virus RNA was widely disseminated, with viremia, oral and rectal shedding, and antigen in spleen and liver. This is the first experimental infection study comparing tissue tropism, viral shedding, and clinical and pathologic effects of six different filoviruses in the Egyptian rousette, a known marburgvirus reservoir. Our results suggest Egyptian rousettes are unlikely sources for ebolaviruses in nature, and support a possible single filovirus—single reservoir host relationship. Full article
Open AccessArticle Evaluation of Signature Erosion in Ebola Virus Due to Genomic Drift and Its Impact on the Performance of Diagnostic Assays
Viruses 2015, 7(6), 3130-3154; doi:10.3390/v7062763
Received: 25 March 2015 / Revised: 11 May 2015 / Accepted: 11 June 2015 / Published: 17 June 2015
Cited by 8 | PDF Full-text (1430 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus
[...] Read more.
Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes. Full article
Open AccessArticle Evaluating Environmental Persistence and Disinfection of the Ebola Virus Makona Variant
Viruses 2015, 7(4), 1975-1986; doi:10.3390/v7041975
Received: 12 January 2015 / Revised: 2 April 2015 / Accepted: 7 April 2015 / Published: 14 April 2015
Cited by 22 | PDF Full-text (661 KB) | HTML Full-text | XML Full-text
Abstract
Background: The current disease outbreak caused by the Ebola virus Makona variant (EBOV/Mak) has led to unprecedented morbidity and lethality given its geographic reach and sustained transmission. Sodium hypochlorite and ethanol are well-accepted decontamination agents, however little published evidence supports the selection of
[...] Read more.
Background: The current disease outbreak caused by the Ebola virus Makona variant (EBOV/Mak) has led to unprecedented morbidity and lethality given its geographic reach and sustained transmission. Sodium hypochlorite and ethanol are well-accepted decontamination agents, however little published evidence supports the selection of appropriate concentrations and contact times. The present study addresses the environmental robustness of EBOV/Mak and evaluates the effectiveness of sodium hypochlorite and ethanol as disinfectants. Methods: EBOV/Mak was suspended in a simulated organic soil load and dried onto surfaces. Viability was measured at 1 hour, 24 hours, 72 hours, and 192 hours. For the evaluation of disinfectants, EBOV/Mak in a simulated organic soil was dried onto stainless steel carriers and disinfected with 0.01% (v/v), 0.1% (v/v), 0.5% (v/v) and 1% (v/v) sodium hypochlorite solutions or 67% (v/v) ethanol at contact times of 1, 5 or 10 minutes. Results: EBOV/Mak persisted longer on steel and plastic surfaces (192 hours) than cotton (<24 hours). Dilute sodium hypochlorite (0.01% and 0.1%) showed little antiviral action, whereas 0.5% and 1% sodium hypochlorite solutions demonstrated recoverable virus at one minute but sterilized surfaces in five minutes. Disinfection with 67% ethanol did not fully clear infectious virions from 3/9 carriers at 1 minute but sterilized all carriers at 5 and 10 minutes. Conclusions: Sodium hypochlorite and ethanol effectively decontaminate EBOV/Mak suspended in a simulated organic load; however, selection of concentration and contact time proves critical. Full article
Open AccessArticle Evaluation of ViroCyt® Virus Counter for Rapid Filovirus Quantitation
Viruses 2015, 7(3), 857-872; doi:10.3390/v7030857
Received: 17 December 2014 / Revised: 6 February 2015 / Accepted: 16 February 2015 / Published: 20 February 2015
Cited by 12 | PDF Full-text (990 KB) | HTML Full-text | XML Full-text
Abstract
Development and evaluation of medical countermeasures for diagnostics, vaccines, and therapeutics requires production of standardized, reproducible, and well characterized virus preparations. For filoviruses this includes plaque assay for quantitation of infectious virus, transmission electron microscopy (TEM) for morphology and quantitation of virus particles,
[...] Read more.
Development and evaluation of medical countermeasures for diagnostics, vaccines, and therapeutics requires production of standardized, reproducible, and well characterized virus preparations. For filoviruses this includes plaque assay for quantitation of infectious virus, transmission electron microscopy (TEM) for morphology and quantitation of virus particles, and real-time reverse transcription PCR for quantitation of viral RNA (qRT-PCR). The ViroCyt® Virus Counter (VC) 2100 (ViroCyt, Boulder, CO, USA) is a flow-based instrument capable of quantifying virus particles in solution. Using a proprietary combination of fluorescent dyes that stain both nucleic acid and protein in a single 30 min step, rapid, reproducible, and cost-effective quantification of filovirus particles was demonstrated. Using a seed stock of Ebola virus variant Kikwit, the linear range of the instrument was determined to be 2.8E+06 to 1.0E+09 virus particles per mL with coefficient of variation ranging from 9.4% to 31.5% for samples tested in triplicate. VC particle counts for various filovirus stocks were within one log of TEM particle counts. A linear relationship was established between the plaque assay, qRT-PCR, and the VC. VC results significantly correlated with both plaque assay and qRT-PCR. These results demonstrated that the VC is an easy, fast, and consistent method to quantify filoviruses in stock preparations. Full article
Open AccessReview Understanding Ebola Virus Transmission
Viruses 2015, 7(2), 511-521; doi:10.3390/v7020511
Received: 7 December 2014 / Revised: 21 January 2015 / Accepted: 29 January 2015 / Published: 3 February 2015
Cited by 19 | PDF Full-text (564 KB) | HTML Full-text | XML Full-text
Abstract
An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data,
[...] Read more.
An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data, we expose important gaps in Ebola virus research pertinent to outbreak situations. We further propose experiments and methods of data collection that will enable scientists to fill these voids in our knowledge about the transmission of Ebola virus. Full article
Figures

Open AccessArticle Modeling of the Ebola Virus Delta Peptide Reveals a Potential Lytic Sequence Motif
Viruses 2015, 7(1), 285-305; doi:10.3390/v7010285
Received: 1 December 2014 / Revised: 12 January 2015 / Accepted: 16 January 2015 / Published: 20 January 2015
Cited by 5 | PDF Full-text (1198 KB) | HTML Full-text | XML Full-text
Abstract
Filoviruses, such as Ebola and Marburg viruses, cause severe outbreaks of human infection, including the extensive epidemic of Ebola virus disease (EVD) in West Africa in 2014. In the course of examining mutations in the glycoprotein gene associated with 2014 Ebola virus (EBOV)
[...] Read more.
Filoviruses, such as Ebola and Marburg viruses, cause severe outbreaks of human infection, including the extensive epidemic of Ebola virus disease (EVD) in West Africa in 2014. In the course of examining mutations in the glycoprotein gene associated with 2014 Ebola virus (EBOV) sequences, a differential level of conservation was noted between the soluble form of glycoprotein (sGP) and the full length glycoprotein (GP), which are both encoded by the GP gene via RNA editing. In the region of the proteins encoded after the RNA editing site sGP was more conserved than the overlapping region of GP when compared to a distant outlier species, Tai Forest ebolavirus. Half of the amino acids comprising the “delta peptide”, a 40 amino acid carboxy-terminal fragment of sGP, were identical between otherwise widely divergent species. A lysine-rich amphipathic peptide motif was noted at the carboxyl terminus of delta peptide with high structural relatedness to the cytolytic peptide of the non-structural protein 4 (NSP4) of rotavirus. EBOV delta peptide is a candidate viroporin, a cationic pore-forming peptide, and may contribute to EBOV pathogenesis. Full article
Figures

Open AccessArticle Immune Memory to Sudan Virus: Comparison between Two Separate Disease Outbreaks
Viruses 2015, 7(1), 37-51; doi:10.3390/v7010037
Received: 28 October 2014 / Accepted: 28 December 2014 / Published: 6 January 2015
Cited by 7 | PDF Full-text (1207 KB) | HTML Full-text | XML Full-text | Correction | Supplementary Files
Abstract
Recovery from ebolavirus infection in humans is associated with the development of both cell-mediated and humoral immune responses. According to recent studies, individuals that did not survive infection with ebolaviruses appear to have lacked a robust adaptive immune response and the expression of
[...] Read more.
Recovery from ebolavirus infection in humans is associated with the development of both cell-mediated and humoral immune responses. According to recent studies, individuals that did not survive infection with ebolaviruses appear to have lacked a robust adaptive immune response and the expression of several early innate response markers. However, a comprehensive protective immune profile has yet to be described. Here, we examine cellular memory immune responses among survivors of two separate Ebolavirus outbreaks (EVDs) due to Sudan virus (SUDV) infection in Uganda—Gulu 2000–2001 and Kibaale 2012. Freshly collected blood samples were stimulated with inactivated SUDV, as well as with recombinant SUDV or Ebola virus (EBOV) GP (GP1–649). In addition, ELISA and plaque reduction neutralization assays were performed to determine anti-SUDV IgG titers and neutralization capacity. Cytokine expression was measured in whole blood cultures in response to SUDV and SUDV GP stimulation in both survivor pools, demonstrating recall responses that indicate immune memory. Cytokine responses between groups were similar but had distinct differences. Neutralizing, SUDV-specific IgG activity against irradiated SUDV and SUDV recombinant proteins were detected in both survivor cohorts. Furthermore, humoral and cell-mediated crossreactivity to EBOV and EBOV recombinant GP1–649 was observed in both cohorts. In conclusion, immune responses in both groups of survivors demonstrate persistent recognition of relevant antigens, albeit larger cohorts are required in order to reach greater statistical significance. The differing cytokine responses between Gulu and Kibaale outbreak survivors suggests that each outbreak may not yield identical memory responses and promotes the merits of studying the immune responses among outbreaks of the same virus. Finally, our demonstration of cross-reactive immune recognition suggests that there is potential for developing cross-protective vaccines for ebolaviruses. Full article

2014

Jump to: 2017, 2016, 2015

Open AccessArticle Euthanasia Assessment in Ebola Virus Infected Nonhuman Primates
Viruses 2014, 6(11), 4666-4682; doi:10.3390/v6114666
Received: 28 October 2014 / Revised: 17 November 2014 / Accepted: 18 November 2014 / Published: 24 November 2014
Cited by 6 | PDF Full-text (782 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Multiple products are being developed for use against filoviral infections. Efficacy for these products will likely be demonstrated in nonhuman primate models of filoviral disease to satisfy licensure requirements under the Animal Rule, or to supplement human data. Typically, the endpoint for efficacy
[...] Read more.
Multiple products are being developed for use against filoviral infections. Efficacy for these products will likely be demonstrated in nonhuman primate models of filoviral disease to satisfy licensure requirements under the Animal Rule, or to supplement human data. Typically, the endpoint for efficacy assessment will be survival following challenge; however, there exists no standardized approach for assessing the health or euthanasia criteria for filovirus-exposed nonhuman primates. Consideration of objective criteria is important to (a) ensure test subjects are euthanized without unnecessary distress; (b) enhance the likelihood that animals exhibiting mild or moderate signs of disease are not prematurely euthanized; (c) minimize the occurrence of spontaneous deaths and loss of end-stage samples; (d) enhance the reproducibility of experiments between different researchers; and (e) provide a defensible rationale for euthanasia decisions that withstands regulatory scrutiny. Historic records were compiled for 58 surviving and non-surviving monkeys exposed to Ebola virus at the US Army Medical Research Institute of Infectious Diseases. Clinical pathology parameters were statistically analyzed and those exhibiting predicative value for survival are reported. These findings may be useful for standardization of objective euthanasia assessments in rhesus monkeys exposed to Ebola virus and may serve as a useful approach for other standardization efforts. Full article
Open AccessLetter Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014
Viruses 2014, 6(11), 4760-4799; doi:10.3390/v6114760
Received: 16 November 2014 / Accepted: 20 November 2014 / Published: 24 November 2014
Cited by 47 | PDF Full-text (832 KB) | HTML Full-text | XML Full-text
Abstract
In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all
[...] Read more.
In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: “Makona”, Middle Africa: “Lomela”) and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures. Full article
Figures

Open AccessArticle A Loop Region in the N-Terminal Domain of Ebola Virus VP40 Is Important in Viral Assembly, Budding, and Egress
Viruses 2014, 6(10), 3837-3854; doi:10.3390/v6103837
Received: 1 July 2014 / Revised: 9 October 2014 / Accepted: 11 October 2014 / Published: 17 October 2014
Cited by 12 | PDF Full-text (1623 KB) | HTML Full-text | XML Full-text
Abstract
Ebola virus (EBOV) causes viral hemorrhagic fever in humans and can have clinical fatality rates of ~60%. The EBOV genome consists of negative sense RNA that encodes seven proteins including viral protein 40 (VP40). VP40 is the major Ebola virus matrix protein and
[...] Read more.
Ebola virus (EBOV) causes viral hemorrhagic fever in humans and can have clinical fatality rates of ~60%. The EBOV genome consists of negative sense RNA that encodes seven proteins including viral protein 40 (VP40). VP40 is the major Ebola virus matrix protein and regulates assembly and egress of infectious Ebola virus particles. It is well established that VP40 assembles on the inner leaflet of the plasma membrane of human cells to regulate viral budding where VP40 can produce virus like particles (VLPs) without other Ebola virus proteins present. The mechanistic details, however, of VP40 lipid-interactions and protein-protein interactions that are important for viral release remain to be elucidated. Here, we mutated a loop region in the N-terminal domain of VP40 (Lys127, Thr129, and Asn130) and find that mutations (K127A, T129A, and N130A) in this loop region reduce plasma membrane localization of VP40. Additionally, using total internal reflection fluorescence microscopy and number and brightness analysis we demonstrate these mutations greatly reduce VP40 oligomerization. Lastly, VLP assays demonstrate these mutations significantly reduce VLP release from cells. Taken together, these studies identify an important loop region in VP40 that may be essential to viral egress. Full article
Figures

Open AccessLetter A Call to Action to Enhance Filovirus Disease Outbreak Preparedness and Response
Viruses 2014, 6(10), 3699-3718; doi:10.3390/v6103699
Received: 8 September 2014 / Revised: 23 September 2014 / Accepted: 23 September 2014 / Published: 30 September 2014
Cited by 4 | PDF Full-text (860 KB) | HTML Full-text | XML Full-text
Abstract
The frequency and magnitude of recognized and declared filovirus-disease outbreaks have increased in recent years, while pathogenic filoviruses are potentially ubiquitous throughout sub-Saharan Africa. Meanwhile, the efficiency and effectiveness of filovirus-disease outbreak preparedness and response efforts are currently limited by inherent challenges and
[...] Read more.
The frequency and magnitude of recognized and declared filovirus-disease outbreaks have increased in recent years, while pathogenic filoviruses are potentially ubiquitous throughout sub-Saharan Africa. Meanwhile, the efficiency and effectiveness of filovirus-disease outbreak preparedness and response efforts are currently limited by inherent challenges and persistent shortcomings. This paper delineates some of these challenges and shortcomings and provides a proposal for enhancing future filovirus-disease outbreak preparedness and response. The proposal serves as a call for prompt action by the organizations that comprise filovirus-disease outbreak response teams, namely, Ministries of Health of outbreak-prone countries, the World Health Organization, Médecins Sans Frontières, the Centers for Disease Control and Prevention—Atlanta, and others. Full article
Open AccessLetter Filovirus RefSeq Entries: Evaluation and Selection of Filovirus Type Variants, Type Sequences, and Names
Viruses 2014, 6(9), 3663-3682; doi:10.3390/v6093663
Received: 17 September 2014 / Accepted: 23 September 2014 / Published: 26 September 2014
Cited by 25 | PDF Full-text (655 KB) | HTML Full-text | XML Full-text
Abstract
Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly
[...] Read more.
Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information’s (NCBI’s) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [<virus name> (<strain>)/<isolation host-suffix>/<country of sampling>/<year of sampling>/<genetic variant designation>-<isolate designation>], we report consensus decisions from a majority of past and currently active filovirus experts on the eight filovirus type variants and isolates to be represented in RefSeq, their final designations, and their associated sequences. Full article
Figures

Open AccessMeeting Report Challenges, Progress, and Opportunities: Proceedings of the Filovirus Medical Countermeasures Workshop
Viruses 2014, 6(7), 2673-2697; doi:10.3390/v6072673
Received: 22 April 2014 / Revised: 1 July 2014 / Accepted: 1 July 2014 / Published: 9 July 2014
Cited by 15 | PDF Full-text (582 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
On August 22–23, 2013, agencies within the United States Department of Defense (DoD) and the Department of Health and Human Services (HHS) sponsored the Filovirus Medical Countermeasures (MCMs) Workshop as an extension of the activities of the Filovirus Animal Non-clinical Group (FANG). The
[...] Read more.
On August 22–23, 2013, agencies within the United States Department of Defense (DoD) and the Department of Health and Human Services (HHS) sponsored the Filovirus Medical Countermeasures (MCMs) Workshop as an extension of the activities of the Filovirus Animal Non-clinical Group (FANG). The FANG is a federally-recognized multi-Agency group established in 2011 to coordinate and facilitate U.S. government (USG) efforts to develop filovirus MCMs. The workshop brought together government, academic and industry experts to consider the needs for filovirus MCMs and evaluate the status of the product development pipeline. This report summarizes speaker presentations and highlights progress and challenges remaining in the field. Full article
Open AccessArticle Analysis of Determinants in Filovirus Glycoproteins Required for Tetherin Antagonism
Viruses 2014, 6(4), 1654-1671; doi:10.3390/v6041654
Received: 25 November 2013 / Revised: 27 March 2014 / Accepted: 30 March 2014 / Published: 9 April 2014
Cited by 8 | PDF Full-text (1763 KB) | HTML Full-text | XML Full-text
Abstract
The host cell protein tetherin can restrict the release of enveloped viruses from infected cells. The HIV-1 protein Vpu counteracts tetherin by removing it from the site of viral budding, the plasma membrane, and this process depends on specific interactions between the transmembrane
[...] Read more.
The host cell protein tetherin can restrict the release of enveloped viruses from infected cells. The HIV-1 protein Vpu counteracts tetherin by removing it from the site of viral budding, the plasma membrane, and this process depends on specific interactions between the transmembrane domains of Vpu and tetherin. In contrast, the glycoproteins (GPs) of two filoviruses, Ebola and Marburg virus, antagonize tetherin without reducing surface expression, and the domains in GP required for tetherin counteraction are unknown. Here, we show that filovirus GPs depend on the presence of their authentic transmembrane domains for virus-cell fusion and tetherin antagonism. However, conserved residues within the transmembrane domain were dispensable for membrane fusion and tetherin counteraction. Moreover, the insertion of the transmembrane domain into a heterologous viral GP, Lassa virus GPC, was not sufficient to confer tetherin antagonism to the recipient. Finally, mutation of conserved residues within the fusion peptide of Ebola virus GP inhibited virus-cell fusion but did not ablate tetherin counteraction, indicating that the fusion peptide and the ability of GP to drive host cell entry are not required for tetherin counteraction. These results suggest that the transmembrane domains of filoviral GPs contribute to tetherin antagonism but are not the sole determinants. Full article
Open AccessArticle Clinical Documentation and Data Transfer from Ebola and Marburg Virus Disease Wards in Outbreak Settings: Health Care Workers’ Experiences and Preferences
Viruses 2014, 6(2), 927-937; doi:10.3390/v6020927
Received: 13 December 2013 / Revised: 8 February 2014 / Accepted: 11 February 2014 / Published: 19 February 2014
Cited by 7 | PDF Full-text (510 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Understanding human filovirus hemorrhagic fever (FHF) clinical manifestations and evaluating treatment strategies require the collection of clinical data in outbreak settings, where clinical documentation has been limited. Currently, no consensus among filovirus outbreak-response organisations guides best practice for clinical documentation and data transfer.
[...] Read more.
Understanding human filovirus hemorrhagic fever (FHF) clinical manifestations and evaluating treatment strategies require the collection of clinical data in outbreak settings, where clinical documentation has been limited. Currently, no consensus among filovirus outbreak-response organisations guides best practice for clinical documentation and data transfer. Semi-structured interviews were conducted with health care workers (HCWs) involved in FHF outbreaks in sub-Saharan Africa, and with HCWs experienced in documenting and transferring data from high-risk areas (isolation wards or biosafety level 4 laboratories). Methods for data documentation and transfer were identified, described in detail and categorised by requirement for electricity and ranked by interviewee preference. Some methods involve removing paperwork and other objects from the filovirus disease ward without disinfection. We believe that if done properly, these methods are reasonably safe for certain settings. However, alternative methods avoiding the removal of objects, or involving the removal of paperwork or objects after non-damaging disinfection, are available. These methods are not only safer, they are also perceived as safer and likely more acceptable to health workers and members of the community. The use of standardised clinical forms is overdue. Experiments with by sunlight disinfection should continue, and non-damaging disinfection of impregnated paper, suitable tablet computers and underwater cameras should be evaluated under field conditions. Full article
Open AccessArticle ABSL-4 Aerobiology Biosafety and Technology at the NIH/NIAID Integrated Research Facility at Fort Detrick
Viruses 2014, 6(1), 137-150; doi:10.3390/v6010137
Received: 25 September 2013 / Revised: 18 December 2013 / Accepted: 20 December 2013 / Published: 7 January 2014
Cited by 4 | PDF Full-text (7919 KB) | HTML Full-text | XML Full-text
Abstract
The overall threat of a viral pathogen to human populations is largely determined by the modus operandi and velocity of the pathogen that is transmitted among humans. Microorganisms that can spread by aerosol are considered a more challenging enemy than those that require
[...] Read more.
The overall threat of a viral pathogen to human populations is largely determined by the modus operandi and velocity of the pathogen that is transmitted among humans. Microorganisms that can spread by aerosol are considered a more challenging enemy than those that require direct body-to-body contact for transmission, due to the potential for infection of numerous people rather than a single individual. Additionally, disease containment is much more difficult to achieve for aerosolized viral pathogens than for pathogens that spread solely via direct person-to-person contact. Thus, aerobiology has become an increasingly necessary component for studying viral pathogens that are naturally or intentionally transmitted by aerosol. The goal of studying aerosol viral pathogens is to improve public health preparedness and medical countermeasure development. Here, we provide a brief overview of the animal biosafety level 4 Aerobiology Core at the NIH/NIAID Integrated Research Facility at Fort Detrick, Maryland, USA. Full article
Figures

Journal Contact

MDPI AG
Viruses Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
E-Mail: 
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Viruses Edit a special issue Review for Viruses
loading...
Back to Top