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Pathogenesis of Emerging Viral Infections
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Pathogenesis of Emerging Viral Infections

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

Deadline for manuscript submissions: closed (15 November 2019) | Viewed by 77326

Special Issue Editors

Dr. Jason Kindrachuk

E-Mail Website
Guest Editor
Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada
Interests: emerging and re-emerging viruses; molecular pathogenesis
Special Issues, Collections and Topics in MDPI journals
Dr. Daniel S. Chertow

E-Mail Website
Guest Editor
Critical Care Medicine Department, National Institutes of Health Clinical Center, Laboratory of Immunoregulation, National Institute of Allergy and Infections Diseases, Bethesda, MD, USA
Interests: Pathogenesis and treatment of severe emerging viral infections

Special Issue Information

Dear Colleagues,

Emerging viruses pose a significant threat to global human and animal health, and outbreaks of these pathogens are increasing in frequency due to changing socio-economic, environmental, and ecological factors. In recent years, multiple zoonotic viruses, including Ebola virus, Middle East respiratory syndrome coronavirus, and Zika virus, have emerged or re-emerged as public health threats. In outbreak ‘hotspots’, limitations in resource capacity or control often hamper timely and effective medical and public health response efforts. Further, emerging viral infections often induce severe illness, with few or no available therapies to limit disease morbidity and mortality. Improved insight into the molecular processes that contribute to organ injury and repair is needed to guide optimal care and the development of efficacious therapies. To this end, better integration of basic and clinical research efforts is required to accelerate breakthrough translational research. Detailed molecular investigations of the clinical and pathologic manifestations of emerging viral infections will provide important insight into disease pathogenesis and advance therapeutic discovery.

Dr. Jason Kindrachuk
Dr. Daniel S. Chertow
Guest Editors

Manuscript Submission Information

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Keywords

  • Emerging viruses
  • Viral pathogenesis
  • Disease mechanisms
  • Therapeutic discovery

Published Papers (14 papers)

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Research

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19 pages, 3032 KiB  
Article
Obstetric Ultrasonography to Detect Fetal Abnormalities in a Mouse Model for Zika Virus Infection
by Dominik Forster, Jan Hendrik Schwarz, Katrin Brosinski, Ulrich Kalinke, Gerd Sutter and Asisa Volz
Viruses 2020, 12(1), 72; https://doi.org/10.3390/v12010072 - 07 Jan 2020
Cited by 3 | Viewed by 3788
Abstract
In 2015 Zika virus (ZIKV) emerged for the first time in South America. The following ZIKV epidemic resulted in the appearance of a clinical phenotype with microcephaly and other severe malformations in newborns. So far, mechanisms of ZIKV induced damage to the fetus [...] Read more.
In 2015 Zika virus (ZIKV) emerged for the first time in South America. The following ZIKV epidemic resulted in the appearance of a clinical phenotype with microcephaly and other severe malformations in newborns. So far, mechanisms of ZIKV induced damage to the fetus are not completely understood. Previous data suggest that ZIKV may bypass the placenta to reach the fetus. Thus, animal models for ZIKV infection are important to facilitate studies about ZIKV infection during pregnancy. Here, we used ultrasound based imaging (USI) to characterize ZIKV induced pathogenesis in the pregnant Type I interferon receptor-deficient (IFNAR-/-) mouse model. Based on USI we suggest the placenta to be a primary target organ of ZIKV infection enabling ZIKV spreading to the fetus. Moreover, in addition to direct infection of the fetus, the placental ZIKV infection may cause an indirect damage to the fetus through reduced uteroplacental perfusion leading to intrauterine growth retardation (IUGR) and fetal complications as early as embryonic day (ED) 12.5. Our data confirmed the capability of USI to characterize ZIKV induced modifications in mouse fetuses. Data from further studies using USI to monitor ZIKV infections will contribute to a better understanding of ZIKV infection in pregnant IFNAR-/- mice. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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21 pages, 1790 KiB  
Article
H7N9 Influenza Virus Containing a Polybasic HA Cleavage Site Requires Minimal Host Adaptation to Obtain a Highly Pathogenic Disease Phenotype in Mice
by Mable Chan, Anders Leung, Tamiko Hisanaga, Brad Pickering, Bryan D. Griffin, Robert Vendramelli, Nikesh Tailor, Gary Wong, Yuhai Bi, Shawn Babiuk, Yohannes Berhane and Darwyn Kobasa
Viruses 2020, 12(1), 65; https://doi.org/10.3390/v12010065 - 05 Jan 2020
Cited by 7 | Viewed by 3737
Abstract
Low pathogenic avian influenza (LPAI) H7N9 viruses have recently evolved to gain a polybasic cleavage site in the hemagglutinin (HA) protein, resulting in variants with increased lethality in poultry that meet the criteria for highly pathogenic avian influenza (HPAI) viruses. Both LPAI and [...] Read more.
Low pathogenic avian influenza (LPAI) H7N9 viruses have recently evolved to gain a polybasic cleavage site in the hemagglutinin (HA) protein, resulting in variants with increased lethality in poultry that meet the criteria for highly pathogenic avian influenza (HPAI) viruses. Both LPAI and HPAI variants can cause severe disease in humans (case fatality rate of ~40%). Here, we investigated the virulence of HPAI H7N9 viruses containing a polybasic HA cleavage site (H7N9-PBC) in mice. Inoculation of mice with H7N9-PBC did not result in observable disease; however, mice inoculated with a mouse-adapted version of this virus, generated by a single passage in mice, caused uniformly lethal disease. In addition to the PBC site, we identified three other mutations that are important for host-adaptation and virulence in mice: HA (A452T), PA (D347G), and PB2 (M483K). Using reverse genetics, we confirmed that the HA mutation was the most critical for increased virulence in mice. Our study identifies additional disease determinants in a mammalian model for HPAI H7N9 virus. Furthermore, the ease displayed by the virus to adapt to a new host highlights the potential for H7N9-PBC viruses to rapidly acquire mutations that may enhance their risk to humans or other animal species. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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24 pages, 2635 KiB  
Article
A Soluble Version of Nipah Virus Glycoprotein G Delivered by Vaccinia Virus MVA Activates Specific CD8 and CD4 T Cells in Mice
by Georgia Kalodimou, Svenja Veit, Sylvia Jany, Ulrich Kalinke, Christopher C. Broder, Gerd Sutter and Asisa Volz
Viruses 2020, 12(1), 26; https://doi.org/10.3390/v12010026 - 24 Dec 2019
Cited by 22 | Viewed by 5336
Abstract
Nipah virus (NiV) is an emerging zoonotic virus that is transmitted by bats to humans and to pigs, causing severe respiratory disease and often fatal encephalitis. Antibodies directed against the NiV-glycoprotein (G) protein are known to play a major role in clearing NiV [...] Read more.
Nipah virus (NiV) is an emerging zoonotic virus that is transmitted by bats to humans and to pigs, causing severe respiratory disease and often fatal encephalitis. Antibodies directed against the NiV-glycoprotein (G) protein are known to play a major role in clearing NiV infection and in providing vaccine-induced protective immunity. More recently, T cells have been also shown to be involved in recovery from NiV infection. So far, relatively little is known about the role of T cell responses and the antigenic targets of NiV-G that are recognized by CD8 T cells. In this study, NiV-G protein served as the target immunogen to activate NiV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for the generation of MVA–NiV-G candidate vaccines expressing different versions of recombinant NiV-G. Overlapping peptides covering the entire NiV-G protein were used to identify major histocompatibility complex class I/II-restricted T cell responses in type I interferon receptor-deficient (IFNAR−/−) mice after vaccination with the MVA–NiV-G candidate vaccines. We have identified an H2-b-restricted nonamer peptide epitope with CD8 T cell antigenicity and a H2-b 15mer with CD4 T cell antigenicity in the NiV-G protein. The identification of this epitope and the availability of the MVA–NiV-G candidate vaccines will help to evaluate NiV-G-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of NiV-G infection. Of note, a soluble version of NiV-G was advantageous in activating NiV-G-specific cellular immune responses using these peptides. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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13 pages, 2644 KiB  
Article
A Novel Mechanism for Zika Virus Host-Cell Binding
by Courtney A. Rieder, Jonathan Rieder, Sebastién Sannajust, Diana Goode, Ramaz Geguchadze, Ryan F. Relich, Derek C. Molliver, Tamara E. King, James Vaughn and Meghan May
Viruses 2019, 11(12), 1101; https://doi.org/10.3390/v11121101 - 28 Nov 2019
Cited by 4 | Viewed by 3149
Abstract
Zika virus (ZIKV) recently emerged in the Western Hemisphere with previously unrecognized or unreported clinical presentations. Here, we identify two putative binding mechanisms of ancestral and emergent ZIKV strains featuring the envelope (E) protein residue asparagine 154 (ASN154) and viral phosphatidylserine (PS). Synthetic [...] Read more.
Zika virus (ZIKV) recently emerged in the Western Hemisphere with previously unrecognized or unreported clinical presentations. Here, we identify two putative binding mechanisms of ancestral and emergent ZIKV strains featuring the envelope (E) protein residue asparagine 154 (ASN154) and viral phosphatidylserine (PS). Synthetic peptides representing the region containing ASN154 from strains PRVABC59 (Puerto Rico 2015) and MR_766 (Uganda 1947) were exposed to neuronal cells and fibroblasts to model ZIKV E protein/cell interactions and bound MDCK or Vero cells and primary neurons significantly. Peptides significantly inhibited Vero cell infectivity by ZIKV strains MR_766 and PRVABC59, indicating that this region represents a putative binding mechanism of ancestral African ZIKV strains and emergent Western Hemisphere strains. Pretreatment of ZIKV strains MR_766 and PRVABC59 with the PS-binding protein annexin V significantly inhibited replication of PRVABC59 but not MR_766, suggesting that Western hemisphere strains may additionally be capable of utilizing PS-mediated entry to infect host cells. These data indicate that the region surrounding E protein ASN154 is capable of binding fibroblasts and primary neuronal cells and that PS-mediated entry may be a secondary mechanism for infectivity utilized by Western Hemisphere strains. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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16 pages, 3352 KiB  
Article
Aptamer Profiling of A549 Cells Infected with Low-Pathogenicity and High-Pathogenicity Influenza Viruses
by Kevin M. Coombs, Philippe F. Simon, Nigel J. McLeish, Ali Zahedi-Amiri and Darwyn Kobasa
Viruses 2019, 11(11), 1028; https://doi.org/10.3390/v11111028 - 05 Nov 2019
Cited by 7 | Viewed by 3779
Abstract
Influenza A viruses (IAVs) are important animal and human emerging and re-emerging pathogens that are responsible for yearly seasonal epidemics and sporadic pandemics. IAVs cause a wide range of clinical illnesses, from relatively mild infections by seasonal strains, to acute respiratory distress during [...] Read more.
Influenza A viruses (IAVs) are important animal and human emerging and re-emerging pathogens that are responsible for yearly seasonal epidemics and sporadic pandemics. IAVs cause a wide range of clinical illnesses, from relatively mild infections by seasonal strains, to acute respiratory distress during infections with highly pathogenic avian IAVs (HPAI). For this study, we infected A549 human lung cells with lab prototype A/PR/8/34 (H1N1) (PR8), a seasonal H1N1 (RV733), the 2009 pandemic H1N1 (pdm09), or with two avian strains, an H5N1 HPAI strain or an H7N9 strain that has low pathogenicity in birds but high pathogenicity in humans. We used a newly-developed aptamer-based multiplexed technique (SOMAscan®) to examine >1300 human lung cell proteins affected by the different IAV strains, and identified more than 500 significantly dysregulated cellular proteins. Our analyses indicated that the avian strains induced more profound changes in the A549 global proteome compared to all tested low-pathogenicity H1N1 strains. The PR8 strain induced a general activation, primarily by upregulating many immune molecules, the seasonal RV733 and pdm09 strains had minimal effect upon assayed molecules, and the avian strains induced significant downregulation, primarily in antimicrobial response, cardiovascular and post-translational modification systems. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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18 pages, 1460 KiB  
Article
Generation and Characterization of a Mouse-Adapted Makona Variant of Ebola Virus
by Mable Chan, Anders Leung, Bryan D. Griffin, Robert Vendramelli, Nikesh Tailor, Kevin Tierney, Jonathan Audet and Darwyn Kobasa
Viruses 2019, 11(11), 987; https://doi.org/10.3390/v11110987 - 26 Oct 2019
Cited by 11 | Viewed by 3650
Abstract
Ebola virus (EBOV) is a zoonotic pathogen that poses a significant threat to public health, causing sporadic yet devastating outbreaks that have the potential to spread worldwide, as demonstrated during the 2013–2016 West African outbreak. Mouse models of infection are important tools for [...] Read more.
Ebola virus (EBOV) is a zoonotic pathogen that poses a significant threat to public health, causing sporadic yet devastating outbreaks that have the potential to spread worldwide, as demonstrated during the 2013–2016 West African outbreak. Mouse models of infection are important tools for the development of therapeutics and vaccines. Exposure of immunocompetent mice to clinical isolates of EBOV is nonlethal; consequently, EBOV requires prior adaptation in mice to cause lethal disease. Until now, the only immunocompetent EBOV mouse model was based on the Mayinga variant, which was isolated in 1976. Here, we generated a novel mouse-adapted (MA)-EBOV based on the 2014 Makona isolate by inserting EBOV/Mayinga-MA mutations into the EBOV/Makona genome, followed by serial passaging of the rescued virus in suckling mice. The resulting EBOV/Makona-MA causes lethal disease in adult immunocompetent mice within 6 to 9 days and has a lethal dose (LD50) of 0.004 plaque forming units (PFU). Two additional mutations emerged after mouse-adaptation in the viral nucleoprotein (NP) and membrane-associated protein VP24. Using reverse genetics, we found the VP24 mutation to be critical for EBOV/Makona-MA virulence. EBOV/Makona-MA infected mice that presented with viremia, high viral burden in organs, increased release of pro-inflammatory cytokines/chemokines, and lymphopenia. Our mouse model will help advance pre-clinical development of countermeasures against contemporary EBOV variants. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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15 pages, 7397 KiB  
Article
Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine
by Petter I. Andersen, Klara Krpina, Aleksandr Ianevski, Nastassia Shtaida, Eunji Jo, Jaewon Yang, Sandra Koit, Tanel Tenson, Veijo Hukkanen, Marit W. Anthonsen, Magnar Bjoras, Magnus Evander, Marc P. Windisch, Eva Zusinaite and Denis E. Kainov
Viruses 2019, 11(10), 964; https://doi.org/10.3390/v11100964 - 18 Oct 2019
Cited by 59 | Viewed by 6523
Abstract
Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play [...] Read more.
Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FLUAV), niclosamide against HSV-2, brequinar against human immunodeficiency virus 1 (HIV-1), and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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16 pages, 5015 KiB  
Article
BK Virus Replication in the Glomerular Vascular Unit: Implications for BK Virus Associated Nephropathy
by Waldemar Popik, Atanu K. Khatua, Noyna F. Fabre, James E. K. Hildreth and Donald J. Alcendor
Viruses 2019, 11(7), 583; https://doi.org/10.3390/v11070583 - 27 Jun 2019
Cited by 12 | Viewed by 4396
Abstract
Background: BK polyomavirus (BKV) reactivates from latency after immunosuppression in renal transplant patients, resulting in BKV-associated nephropathy (BKVAN). BKVAN has emerged as an important cause of graft dysfunction and graft loss among transplant patients. BKV infection in kidney transplant patients has increased over [...] Read more.
Background: BK polyomavirus (BKV) reactivates from latency after immunosuppression in renal transplant patients, resulting in BKV-associated nephropathy (BKVAN). BKVAN has emerged as an important cause of graft dysfunction and graft loss among transplant patients. BKV infection in kidney transplant patients has increased over recent decades which correlates with the use of more potent immunosuppressive therapies. BKV infection of the Glomerular Vascular Unit (GVU) consisting of podocytes, mesangial cells, and glomerular endothelial cells could lead to glomerular inflammation and contribute to renal fibrosis. The effects of BKV on GVU infectivity have not been reported. methods: We infected GVU cells with the Dunlop strain of BKV. Viral infectivity was analyzed by microscopy, immunofluorescence, Western blot analysis, and quantitative RT-PCR (qRT-PCR). The expression of specific proinflammatory cytokines induced by BKV was analyzed by qRT-PCR. Results: BKV infection of podocytes, mesangial cells, and glomerular endothelial cells was confirmed by qRT-PCR and positive staining with antibodies to the BKV VP1 major capsid protein, or the SV40 Large T-Antigen. The increased transcriptional expression of interferon gamma-induced protein 10 (CXCL10/IP-10) and interferon beta (IFNβ) was detected in podocytes and mesangial cells at 96 h post-infection. conclusions: All cellular components of the GVU are permissive for BKV replication. Cytopathic effects induced by BKV in podocytes and glomerular endothelial cells and the expression of CXCL10 and IFNβ genes by podocytes and mesangial cells may together contribute to glomerular inflammation and cytopathology in BKVAN. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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14 pages, 9976 KiB  
Article
A Stillborn Multiple Organs’ Investigation from a Maternal DENV-4 Infection: Histopathological and Inflammatory Mediators Characterization
by Priscila Nunes, Rita Nogueira, Janice Coelho, Francisco Rodrigues, Natália Salomão, Carollina José, Jorge de Carvalho, Kíssila Rabelo, Elzinandes de Azeredo, Rodrigo Basílio-de-Oliveira, Carlos Basílio-de-Oliveira, Flávia dos Santos and Marciano Paes
Viruses 2019, 11(4), 319; https://doi.org/10.3390/v11040319 - 02 Apr 2019
Cited by 23 | Viewed by 4037
Abstract
Dengue virus (DENV) is an emerging virus involved in outbreaks in Brazil. The association between the virus and vertical transmission, with disorders in the placenta, has raised a worldwide concern. On the 29th gestational week, a pregnant woman presented severe complications due to [...] Read more.
Dengue virus (DENV) is an emerging virus involved in outbreaks in Brazil. The association between the virus and vertical transmission, with disorders in the placenta, has raised a worldwide concern. On the 29th gestational week, a pregnant woman presented severe complications due to a DENV infection leading to maternal and fetus death. Postmortem analysis of fetal organs demonstrated the presence of DENV using reverse transcriptase polymerase chain reaction (RT-PCR) in the fetal brain and DENV non-structural protein 3 (NS3) staining in placenta and several peripheral fetal tissues, such as the brain, liver, lungs, and spleen. Histological analysis of the placenta and fetal organs revealed different types of tissue abnormalities, which included inflammation, hemorrhage, edema, and necrosis in placenta and tissue disorganization in the fetus, such as spongiform parenchyma, microglial inflammation, steatosis, hyalinose arteriolar, inflammatory cells in the alveolar septa, and disorganization of the lymphoid follicle. Increased cellularity (macrophage, Hofbauer cells and TCD8+ lymphocytes) and up-regulation of inflammatory mediators such as IFN-γ, TNF-α, RANTES/CCL5, MCP1/CCL2, and VEGF/R2 were detected in the liver, lung, spleen, brain, and placenta, supporting placental and fetus peripheral tissues inflammation. Maternal infection leading to the production of those vascular mediators may alter the vascular permeability, facilitating the virus entry and tissue and barrier dysfunction. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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17 pages, 2704 KiB  
Article
Clinical, Histopathologic, and Immunohistochemical Characterization of Experimental Marburg Virus Infection in A Natural Reservoir Host, the Egyptian Rousette Bat (Rousettus aegyptiacus)
by Megan E.B. Jones, Brian R. Amman, Tara K. Sealy, Luke S. Uebelhoer, Amy J. Schuh, Timothy Flietstra, Brian H. Bird, JoAnn D. Coleman-McCray, Sherif R. Zaki, Stuart T. Nichol and Jonathan S. Towner
Viruses 2019, 11(3), 214; https://doi.org/10.3390/v11030214 - 02 Mar 2019
Cited by 28 | Viewed by 5367
Abstract
Egyptian rousette bats (Rousettus aegyptiacus) are natural reservoir hosts of Marburg virus (MARV), and Ravn virus (RAVV; collectively called marburgviruses) and have been linked to human cases of Marburg virus disease (MVD). We investigated the clinical and pathologic effects of experimental [...] Read more.
Egyptian rousette bats (Rousettus aegyptiacus) are natural reservoir hosts of Marburg virus (MARV), and Ravn virus (RAVV; collectively called marburgviruses) and have been linked to human cases of Marburg virus disease (MVD). We investigated the clinical and pathologic effects of experimental MARV infection in Egyptian rousettes through a serial euthanasia study and found clear evidence of mild but transient disease. Three groups of nine, captive-born, juvenile male bats were inoculated subcutaneously with 10,000 TCID50 of Marburg virus strain Uganda 371Bat2007, a minimally passaged virus originally isolated from a wild Egyptian rousette. Control bats (n = 3) were mock-inoculated. Three animals per day were euthanized at 3, 5–10, 12 and 28 days post-inoculation (DPI); controls were euthanized at 28 DPI. Blood chemistry analyses showed a mild, statistically significant elevation in alanine aminotransferase (ALT) at 3, 6 and 7 DPI. Lymphocyte and monocyte counts were mildly elevated in inoculated bats after 9 DPI. Liver histology revealed small foci of inflammatory infiltrate in infected bats, similar to lesions previously described in wild, naturally-infected bats. Liver lesion severity scores peaked at 7 DPI, and were correlated with both ALT and hepatic viral RNA levels. Immunohistochemical staining detected infrequent viral antigen in liver (3–8 DPI, n = 8), spleen (3–7 DPI, n = 8), skin (inoculation site; 3–12 DPI, n = 20), lymph nodes (3–10 DPI, n = 6), and oral submucosa (8–9 DPI, n = 2). Viral antigen was present in histiocytes, hepatocytes and mesenchymal cells, and in the liver, antigen staining co-localized with inflammatory foci. These results show the first clear evidence of very mild disease caused by a filovirus in a reservoir bat host and provide support for our experimental model of this virus-reservoir host system. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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12 pages, 793 KiB  
Review
A Comparative Analysis of Factors Influencing Two Outbreaks of Middle Eastern Respiratory Syndrome (MERS) in Saudi Arabia and South Korea
by Marnie Willman, Darwyn Kobasa and Jason Kindrachuk
Viruses 2019, 11(12), 1119; https://doi.org/10.3390/v11121119 - 03 Dec 2019
Cited by 37 | Viewed by 6738
Abstract
In 2012, an emerging viral infection was identified in Saudi Arabia that subsequently spread to 27 additional countries globally, though cases may have occurred elsewhere. The virus was ultimately named Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV), and has been endemic in Saudi Arabia [...] Read more.
In 2012, an emerging viral infection was identified in Saudi Arabia that subsequently spread to 27 additional countries globally, though cases may have occurred elsewhere. The virus was ultimately named Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV), and has been endemic in Saudi Arabia since 2012. As of September 2019, 2468 laboratory-confirmed cases with 851 associated deaths have occurred with a case fatality rate of 34.4%, according to the World Health Organization. An imported case of MERS occurred in South Korea in 2015, stimulating a multi-month outbreak. Several distinguishing factors emerge upon epidemiological and sociological analysis of the two outbreaks including public awareness of the MERS outbreak, and transmission and synchronization of governing healthcare bodies. South Korea implemented a stringent healthcare model that protected patients and healthcare workers alike through prevention and high levels of public information. In addition, many details about MERS-CoV virology, transmission, pathological progression, and even the reservoir, remain unknown. This paper aims to delineate the key differences between the two regional outbreaks from both a healthcare and personal perspective including differing hospital practices, information and public knowledge, cultural practices, and reservoirs, among others. Further details about differing emergency outbreak responses, public information, and guidelines put in place to protect hospitals and citizens could improve the outcome of future MERS outbreaks. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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11 pages, 1584 KiB  
Review
The Roles of Ebola Virus Soluble Glycoprotein in Replication, Pathogenesis, and Countermeasure Development
by Wenjun Zhu, Logan Banadyga, Karla Emeterio, Gary Wong and Xiangguo Qiu
Viruses 2019, 11(11), 999; https://doi.org/10.3390/v11110999 - 31 Oct 2019
Cited by 24 | Viewed by 6049
Abstract
Ebola virus (EBOV) is a highly lethal pathogen that has caused several outbreaks of severe hemorrhagic fever in humans since its emergence in 1976. The EBOV glycoprotein (GP1,2) is the sole viral envelope protein and a major component of immunogenicity; it [...] Read more.
Ebola virus (EBOV) is a highly lethal pathogen that has caused several outbreaks of severe hemorrhagic fever in humans since its emergence in 1976. The EBOV glycoprotein (GP1,2) is the sole viral envelope protein and a major component of immunogenicity; it is encoded by the GP gene along with two truncated versions: soluble GP (sGP) and small soluble GP (ssGP). sGP is, in fact, the primary product of the GP gene, and it is secreted in abundance during EBOV infection. Since sGP shares large portions of its sequence with GP1,2, it has been hypothesized that sGP may subvert the host immune response by inducing antibodies against sGP rather than GP1,2. Several reports have shown that sGP plays multiple roles that contribute to the complex pathogenesis of EBOV. In this review, we focus on sGP and discuss its possible roles with regards to the pathogenesis of EBOV and the development of specific antiviral drugs. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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23 pages, 1731 KiB  
Review
Viral Innate Immune Evasion and the Pathogenesis of Emerging RNA Virus Infections
by Tessa Nelemans and Marjolein Kikkert
Viruses 2019, 11(10), 961; https://doi.org/10.3390/v11100961 - 18 Oct 2019
Cited by 164 | Viewed by 14186
Abstract
Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and, in particular, the interferon response form the important first line of defence against these viruses. Given their genetic flexibility, these viruses have [...] Read more.
Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and, in particular, the interferon response form the important first line of defence against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by viral infections is less prevalent in the literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging coronaviruses, alphaviruses and flaviviruses. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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9 pages, 387 KiB  
Review
Zika Virus Pathogenesis: From Early Case Reports to Epidemics
by Ryan D. Pardy and Martin J. Richer
Viruses 2019, 11(10), 886; https://doi.org/10.3390/v11100886 - 21 Sep 2019
Cited by 14 | Viewed by 5322
Abstract
For the first 60 years following its isolation, Zika virus (ZIKV) remained a relatively poorly described member of the Flaviviridae family. However, since 2007, it has caused a series of increasingly severe outbreaks and is now associated with neurological symptoms such as Guillain-Barré [...] Read more.
For the first 60 years following its isolation, Zika virus (ZIKV) remained a relatively poorly described member of the Flaviviridae family. However, since 2007, it has caused a series of increasingly severe outbreaks and is now associated with neurological symptoms such as Guillain-Barré syndrome and congenital Zika syndrome (CZS). A number of reports have improved our understanding of rare complications that may be associated with ZIKV infection in adults, the areas of the body to which it spreads, and viral persistence in various tissues. Likewise, studies on the effect of ZIKV infection during pregnancy have identified risk factors for CZS and the impact this syndrome has on early childhood. Understanding these outcomes and the factors that drive ZIKV pathogenesis are key to developing vaccination and therapeutic approaches to avoid these severe and potentially debilitating symptoms. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
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