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Special Issue "Hantaviruses"

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

Deadline for manuscript submissions: closed (31 July 2019).

Special Issue Editor

Guest Editor
Dr. Tony Schountz

Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, USA
Website | E-Mail
Interests: rodent- and bat-borne viruses

Special Issue Information

Dear Colleagues,

Hantaviruses have world-wide distribution, and some have been shown to cause disease in humans, with compelling evidence of inflammatory immunopathology. More than 100,000 cases of hantavirus disease occur each year, with mortality rates ranging from 2% to 36%. Pathogenic hantaviruses are principally hosted by peridomestic rodents, and despite their public health significance, there are few therapies or vaccines available. In contrast to humans, there is no evidence that hantaviruses cause meaningful disease in their reservoir hosts, which appear to elicit anti-inflammatory immune responses. Recent discoveries have shown that hantaviruses are also hosted by moles, shrews, and bats, but very little has been learned about these hantaviruses. Thus, it is unclear what zoonotic potential these viruses might have. Investigations into these viruses have been limited compared with rodent-borne hantaviruses, principally due to a lack of suitable ecological studies and animal models. This Special Issue will cover the recent developments in hantavirus biology, including ecology, in the context of reservoir hosts, pathogenesis, mechanisms of virus–host cell interaction, animal models for reservoirs, as well as pathogenesis studies, and new approaches to the clinical management of the disease.

Dr. Tony Schountz
Guest Editor

Manuscript Submission Information

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Keywords

  • hantavirus
  • zoonosis
  • virus ecology
  • reservoir hosts
  • hantavirus cardiopulmonary syndrome
  • hemorrhagic fever with renal syndrome

Published Papers (20 papers)

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Research

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Open AccessArticle
Exposure to Hantavirus is a Risk Factor Associated with Kidney Diseases in Sri Lanka: A Cross Sectional Study
Viruses 2019, 11(8), 700; https://doi.org/10.3390/v11080700
Received: 31 May 2019 / Revised: 16 July 2019 / Accepted: 30 July 2019 / Published: 31 July 2019
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Abstract
Chronic kidney disease of unknown etiology (CKDu) imposes a substantial burden on public health in Sri Lankan agricultural communities. High seroprevalences of hantavirus have been reported in CKDu patients in several locations of Sri Lanka. We carried out a cross-sectional study followed by [...] Read more.
Chronic kidney disease of unknown etiology (CKDu) imposes a substantial burden on public health in Sri Lankan agricultural communities. High seroprevalences of hantavirus have been reported in CKDu patients in several locations of Sri Lanka. We carried out a cross-sectional study followed by an unmatched case-control comparison in two geographically distinct areas of Sri Lanka, Girandurukotte (CKDu endemic) and Kandy (CKDu non-endemic) to determine whether exposure to hantaviruses is a potential risk factor in patients with kidney disease. An indirect immunofluorescent antibody assay using two antigens, Thailand orthohantavirus-infected and recombinant N protein-expressing Vero E6 cells, were used for serodiagnosis. Participants’ demographic and other socio-economic data were collected through a structured questionnaire. Fifty kidney disease patients and 270 controls from Kandy and 104 kidney disease patients and 242 controls from Girandurukotte were examined. Seropositivities were 50% and 17.4% in kidney patients and controls, respectively, in Girandurukotte, and they were 18% and 7% in Kandy. The odds of exposure to hantaviruses were higher for kidney disease patients than for controls in both Girandurukotte (OR:3.66, 95% CI:2.01 to 6.64) and Kandy (OR:2.64, 95% CI:1.07 to 6.54) in binary logistic regression models. According to statistical analysis, individuals exposed to hantaviruses had a higher risk of developing renal impairment. Therefore, hantavirus infection might be an important risk factor for development of kidney disease in Sri Lanka. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessArticle
Prediction of the Spatial Origin of Puumala Virus Infections Using L Segment Sequences Derived from a Generic Screening PCR
Viruses 2019, 11(8), 694; https://doi.org/10.3390/v11080694
Received: 30 May 2019 / Revised: 12 July 2019 / Accepted: 27 July 2019 / Published: 30 July 2019
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Abstract
To screen diagnostic specimens for the presence of hantavirus genomes or to identify new hantaviruses in nature, the pan-hanta L-PCR assay, a broadly reactive nested reverse transcription polymerase chain reaction (RT-PCR) assay targeting the L segment, is highly preferred over other assays because [...] Read more.
To screen diagnostic specimens for the presence of hantavirus genomes or to identify new hantaviruses in nature, the pan-hanta L-PCR assay, a broadly reactive nested reverse transcription polymerase chain reaction (RT-PCR) assay targeting the L segment, is highly preferred over other assays because of its universality and high sensitivity. In contrast, the geographic allocation of Puumala virus strains to defined outbreak regions in Germany was previously done based on S segment sequences. We show that the routinely generated partial L segment sequences resulting from the pan-hanta L-PCR assay provide sufficient phylogenetic signal to inform the molecular epidemiology of the Puumala virus. Consequently, an additional S segment analysis seems no longer necessary for the identification of the spatial origin of a virus strain. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessArticle
Platelet Count in Patients with Mild Disease at Admission is Associated with Progression to Severe Hantavirus Cardiopulmonary Syndrome
Viruses 2019, 11(8), 693; https://doi.org/10.3390/v11080693
Received: 1 June 2019 / Revised: 18 July 2019 / Accepted: 19 July 2019 / Published: 30 July 2019
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Abstract
Background: Hantavirus cardiopulmonary syndrome (HCPS) has a mortality up to 35–40% and its treatment is mainly supportive. A variable to predict progression from mild to severe disease is unavailable. This study was performed in patients with documented infection by Andes orthohantavirus, and the [...] Read more.
Background: Hantavirus cardiopulmonary syndrome (HCPS) has a mortality up to 35–40% and its treatment is mainly supportive. A variable to predict progression from mild to severe disease is unavailable. This study was performed in patients with documented infection by Andes orthohantavirus, and the aim was to find a simple variable to predict progression to moderate/severe HCPS in patients with mild disease at admission. Methods: We performed a retrospective analysis of 175 patients between 2001 and 2018. Patients were categorized into mild, moderate, and severe disease according to organ failure and advanced support need at hospital admission (e.g., mechanical ventilation, vasopressors). Progression to moderate/severe disease was defined accordingly. Clinical and laboratory variables associated with progression were explored. Results: Forty patients with mild disease were identified; 14 of them progressed to moderate/severe disease. Only platelet count was different between those who progressed versus those that did not (37 (34–58) vs. 83 (64–177) K/mm3, p < 0.001). A ROC curve analysis showed an AUC = 0.889 (0.78–1.0) p < 0.001, with a platelet count greater than 115K /mm3 ruling out progression to moderate/severe disease. Conclusions: In patients with mild disease at presentation, platelet count could help to define priority of evacuation to tertiary care centers. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessArticle
Deletions in Genes Participating in Innate Immune Response Modify the Clinical Course of Andes Orthohantavirus Infection
Viruses 2019, 11(8), 680; https://doi.org/10.3390/v11080680
Received: 31 May 2019 / Revised: 28 June 2019 / Accepted: 9 July 2019 / Published: 25 July 2019
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Abstract
Andes orthohantavirus (ANDV) is an important human pathogen causing hantavirus cardiopulmonary syndrome (HCPS) with a fatality rate of 30% in Chile. Around 60% of all cases have a severe clinical course, while the others have a mild clinical course. The main goal of [...] Read more.
Andes orthohantavirus (ANDV) is an important human pathogen causing hantavirus cardiopulmonary syndrome (HCPS) with a fatality rate of 30% in Chile. Around 60% of all cases have a severe clinical course, while the others have a mild clinical course. The main goal of this study was to understand if the genetic variation of patients is associated with the clinical course they develop after ANDV infection. For this, the frequency of copy number variants (CNVs, i.e., deletions and duplications) was studied in 195 patients, 88 with mild and 107 with severe HCPS. CNVs were called from intensity data of the Affymetrix Genome-Wide SNP Array 6.0. The analysis of the data was performed with PennCNV, ParseCNV and R softwares; Results: a deletion of 19, 416 bp in the q31.3 region of chromosome 1 is found more frequently in severe patients (p < 0.05). This region contains Complement Factor H Related (CFHR1) and CFHR3 genes, regulators of the complement cascade. A second deletion of 1.81 kb located in the p13 region of chr20 was significantly more frequent in mild patients (p < 0.05). This region contains the SIRPB1 gene, which participates in the innate immune response, more specifically in neutrophil trans-epithelial migration. Both deletions are associated with the clinical course of HCPS, the first being a risk factor and the second being protective. The participation of genes contained in both deletions in ANDV infection pathophysiology deserves further investigation. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessArticle
Phylogeography of Puumala orthohantavirus in Europe
Viruses 2019, 11(8), 679; https://doi.org/10.3390/v11080679
Received: 29 May 2019 / Revised: 12 July 2019 / Accepted: 22 July 2019 / Published: 24 July 2019
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Abstract
Puumala virus is an RNA virus hosted by the bank vole (Myodes glareolus) and is today present in most European countries. Whilst it is generally accepted that hantaviruses have been tightly co-evolving with their hosts, Puumala virus (PUUV) evolutionary history is still controversial [...] Read more.
Puumala virus is an RNA virus hosted by the bank vole (Myodes glareolus) and is today present in most European countries. Whilst it is generally accepted that hantaviruses have been tightly co-evolving with their hosts, Puumala virus (PUUV) evolutionary history is still controversial and so far has not been studied at the whole European level. This study attempts to reconstruct the phylogeographical spread of modern PUUV throughout Europe during the last postglacial period in the light of an upgraded dataset of complete PUUV small (S) segment sequences and by using most recent computational approaches. Taking advantage of the knowledge on the past migrations of its host, we identified at least three potential independent dispersal routes of PUUV during postglacial recolonization of Europe by the bank vole. From the Alpe-Adrian region (Balkan, Austria, and Hungary) to Western European countries (Germany, France, Belgium, and Netherland), and South Scandinavia. From the vicinity of Carpathian Mountains to the Baltic countries and to Poland, Russia, and Finland. The dissemination towards Denmark and North Scandinavia is more hypothetical and probably involved several independent streams from south and north Fennoscandia. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessArticle
Δccr5 Genotype Is Associated with Mild Form of Nephropathia Epidemica
Viruses 2019, 11(7), 675; https://doi.org/10.3390/v11070675
Received: 24 May 2019 / Revised: 22 June 2019 / Accepted: 17 July 2019 / Published: 23 July 2019
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Abstract
Nephropathia Epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) and linked to hantavirus infection, is endemic in the Republic of Tatarstan. Several genetic markers of HFRS severity have been identified previously, including human leukocyte antigen (HLA) complexes and nucleotide [...] Read more.
Nephropathia Epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) and linked to hantavirus infection, is endemic in the Republic of Tatarstan. Several genetic markers of HFRS severity have been identified previously, including human leukocyte antigen (HLA) complexes and nucleotide polymorphism in the tumor necrosis factor alpha (TNFα) gene. Still, our understanding of the genetic markers of NE severity remains incomplete. The frequency of the C–C chemokine receptor type 5 (CCR5) gene wild type and gene with 32-base-pair deletion (Δ32CCR5) genotypes in 98 NE samples and 592 controls was analyzed using PCR. Along with the serum levels of 94 analytes, a lack of differences in the CCR5 genotype distribution between NE cases and the general population suggests that the CCR5 genotype does not affect susceptibility to hantavirus infection. However, in NE cases, significant variation in the serum levels of the host matrix metalloproteases between functional CCR5 homozygous and Δ32CCR5 heterozygous patients was detected. Also, the oliguric phase was longer, while thrombocyte counts were lower in functional CCR5 homozygous as compared to heterozygous NE cases. Our data, for the first time, presents the potential role of the CCR5 receptor genotype in NE pathogenesis. Our data suggests that NE pathogenesis in functional CCR5 homozygous and heterozygous NE patients differs, where homozygous cases may have more disintegration of the extracellular matrix and potentially more severe disease. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessArticle
The Ecology and Phylogeny of Hosts Drive the Enzootic Infection Cycles of Hantaviruses
Viruses 2019, 11(7), 671; https://doi.org/10.3390/v11070671
Received: 4 June 2019 / Revised: 17 July 2019 / Accepted: 19 July 2019 / Published: 23 July 2019
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Abstract
Hantaviruses (Family: Hantaviridae; genus: Orthohantavirus) and their associated human diseases occur globally and differ according to their geographic distribution. The structure of small mammal assemblages and phylogenetic relatedness among host species are suggested as strong drivers for the maintenance and spread of [...] Read more.
Hantaviruses (Family: Hantaviridae; genus: Orthohantavirus) and their associated human diseases occur globally and differ according to their geographic distribution. The structure of small mammal assemblages and phylogenetic relatedness among host species are suggested as strong drivers for the maintenance and spread of hantavirus infections in small mammals. We developed predictive models for hantavirus infection prevalence in rodent assemblages using defined ecological correlates from our current knowledge of hantavirus-host distributions to provide predictive models at the global and continental scale. We utilized data from published research between 1971–2014 and determined the biological and ecological characteristics of small mammal assemblages to predict the prevalence of hantavirus infections. These models are useful in predicting hantavirus disease outbreaks based on environmental and biological information obtained through the surveillance of rodents. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessArticle
Evaluation of Real-Time RT-PCR for Diagnostic Use in Detection of Puumala Virus
Viruses 2019, 11(7), 661; https://doi.org/10.3390/v11070661
Received: 31 May 2019 / Revised: 4 July 2019 / Accepted: 12 July 2019 / Published: 19 July 2019
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Abstract
Puumala virus (PUUV) is the most common cause of hantavirus infection in Europe, with thousands of cases occurring particularly in Northern, Central and Eastern Europe and Russia. It causes a mild form of hemorrhagic fever with renal syndrome also known as nephropathia epidemica [...] Read more.
Puumala virus (PUUV) is the most common cause of hantavirus infection in Europe, with thousands of cases occurring particularly in Northern, Central and Eastern Europe and Russia. It causes a mild form of hemorrhagic fever with renal syndrome also known as nephropathia epidemica (NE) with clinical picture ranging from mild to severe. Currently, the laboratory diagnosis of NE is mainly based on serology. Here, we evaluated a real-time one-step qRT-PCR (PUUV-qRT-PCR) for detection of PUUV with 238 consecutive diagnostic serum samples from patients with suspected PUUV infection. The PUUV-qRT-PCR was both specific and sensitive for PUUV RNA. The analytical sensitivity (limit of detection) was estimated to be four copies of PUUV per reaction. Altogether 28 out of 30 (93%) PUUV IgM positive samples were positive also for PUUV RNA. No false positives were detected and the specificity was thus 100%. Interestingly, one sample was found positive in PUUV-qRT-PCR prior to subsequent IgM and IgG seroconversion. PUUV-qRT-PCR could be used for diagnostics in the early phase of NE infection and might be helpful especially in the rare severe cases when the patient’s condition may deteriorate rapidly. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessArticle
Vesicular Stomatitis Virus-Based Vaccines Provide Cross-Protection against Andes and Sin Nombre Viruses
Viruses 2019, 11(7), 645; https://doi.org/10.3390/v11070645
Received: 6 May 2019 / Revised: 24 June 2019 / Accepted: 12 July 2019 / Published: 13 July 2019
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Abstract
Andes virus (ANDV) and Sin Nombre virus (SNV) are the main causative agents responsible for hantavirus cardiopulmonary syndrome (HCPS) in the Americas. HCPS is a severe respiratory disease with a high fatality rate for which there are no approved therapeutics or vaccines available. [...] Read more.
Andes virus (ANDV) and Sin Nombre virus (SNV) are the main causative agents responsible for hantavirus cardiopulmonary syndrome (HCPS) in the Americas. HCPS is a severe respiratory disease with a high fatality rate for which there are no approved therapeutics or vaccines available. Some vaccine approaches for HCPS have been tested in preclinical models, but none have been tested in infectious models in regard to their ability to protect against multiple species of HCPS-causing viruses. Here, we utilize recombinant vesicular stomatitis virus-based (VSV) vaccines for Andes virus (ANDV) and Sin Nombre virus (SNV) and assess their ability to provide cross-protection in infectious challenge models. We show that, while both rVSVΔG/ANDVGPC and rVSVΔG/SNVGPC display attenuated growth as compared to wild type VSV, each vaccine is able to induce a cross-reactive antibody response. Both vaccines protected against both homologous and heterologous challenge with ANDV and SNV and prevented HCPS in a lethal ANDV challenge model. This study provides evidence that the development of a single vaccine against HCPS-causing hantaviruses could provide protection against multiple agents. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessArticle
Current Situation and Perspectives on Hantaviruses in Mexico
Viruses 2019, 11(7), 642; https://doi.org/10.3390/v11070642
Received: 17 May 2019 / Revised: 28 June 2019 / Accepted: 9 July 2019 / Published: 12 July 2019
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Abstract
Hantaviruses are transmitted by rodents producing the hantavirus pulmonary syndrome (HPS) in the Americas. Today, no human cases of HPS have been reported in Mexico in spite of similar environmental conditions with Central America and the USA where several cases have occurred. To [...] Read more.
Hantaviruses are transmitted by rodents producing the hantavirus pulmonary syndrome (HPS) in the Americas. Today, no human cases of HPS have been reported in Mexico in spite of similar environmental conditions with Central America and the USA where several cases have occurred. To understand the current situation of hantaviruses in Mexico and the public health risk, a systematic review of studies was conducted reporting hantaviruses in rodents to known state seroprevalence and hantavirus genotypes. Simultaneously, this study identified the potential hantaviruses based on the phylogenetic diversity (PD) of hantaviruses reported in the Americas in hosts with the distribution in Mexico. A total 3862 rodents belonging to 82 species have been tested since 1999 to 2017. Overall, 392 individuals representing 43 rodent species were seropositive, and the seroprevalence ranged from 0 to 69.22%. Seven hantaviruses genotypes have been described in Mexico and three are zoonotic. Four host species of rodents are widely distributed in Mexico harboring the highest PD of viruses. According to the hosts distribution, 16 genotypes could be circulating in Mexico and some of these represent a potential risk for public health. This study proposed multidisciplinary and interinstitutional collaborations to implement systematic surveillance in rodents. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessArticle
Complex History of Codiversification and Host Switching of a Newfound Soricid-Borne Orthohantavirus in North America
Viruses 2019, 11(7), 637; https://doi.org/10.3390/v11070637
Received: 1 June 2019 / Revised: 5 July 2019 / Accepted: 9 July 2019 / Published: 11 July 2019
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Abstract
Orthohantaviruses are tightly linked to the ecology and evolutionary history of their mammalian hosts. We hypothesized that in regions with dramatic climate shifts throughout the Quaternary, orthohantavirus diversity and evolution are shaped by dynamic host responses to environmental change through processes such as [...] Read more.
Orthohantaviruses are tightly linked to the ecology and evolutionary history of their mammalian hosts. We hypothesized that in regions with dramatic climate shifts throughout the Quaternary, orthohantavirus diversity and evolution are shaped by dynamic host responses to environmental change through processes such as host isolation, host switching, and reassortment. Jemez Springs virus (JMSV), an orthohantavirus harbored by the dusky shrew (Sorex monticola) and five close relatives distributed widely in western North America, was used to test this hypothesis. Total RNAs, extracted from liver or lung tissue from 164 shrews collected from western North America during 1983–2007, were analyzed for orthohantavirus RNA by reverse transcription polymerase chain reaction (RT-PCR). Phylogenies inferred from the L-, M-, and S-segment sequences of 30 JMSV strains were compared with host mitochondrial cytochrome b. Viral clades largely corresponded to host clades, which were primarily structured by geography and were consistent with hypothesized post-glacial expansion. Despite an overall congruence between host and viral gene phylogenies at deeper scales, phylogenetic signals were recovered that also suggested a complex pattern of host switching and at least one reassortment event in the evolutionary history of JMSV. A fundamental understanding of how orthohantaviruses respond to periods of host population expansion, contraction, and secondary host contact is the key to establishing a framework for both more comprehensive understanding of orthohantavirus evolutionary dynamics and broader insights into host–pathogen systems. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessArticle
Seoul Virus Tropism and Pathology in Naturally Infected Feeder Rats
Viruses 2019, 11(6), 531; https://doi.org/10.3390/v11060531
Received: 15 April 2019 / Revised: 24 May 2019 / Accepted: 5 June 2019 / Published: 7 June 2019
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Abstract
Seoul virus (SEOV) is a zoonotic orthohantavirus carried by black and brown rats, and can cause hemorrhagic fever with renal syndrome in humans. Human cases of SEOV virus infection have most recently been reported in the USA, United Kingdom, France and the Netherlands [...] Read more.
Seoul virus (SEOV) is a zoonotic orthohantavirus carried by black and brown rats, and can cause hemorrhagic fever with renal syndrome in humans. Human cases of SEOV virus infection have most recently been reported in the USA, United Kingdom, France and the Netherlands and were primarily associated with contact with pet rats and feeder rats. Infection of rats results in an asymptomatic but persistent infection. Little is known about the cell tropism of SEOV in its reservoir and most available data is based on experimental infection studies in which rats were inoculated via a route which does not recapitulate virus transmission in nature. Here we report the histopathological analysis of SEOV cell tropism in key target organs following natural infection of a cohort of feeder rats, comprising 19 adults and 11 juveniles. All adult rats in this study were positive for SEOV specific antibodies and viral RNA in their tissues. One juvenile rat was seropositive, but negative in the rRT-PCR. Of the 19 adult rats of which subsequently additional organs were tested, SEOV RNA was detected in all lungs, followed by kidney (79%) and liver (74%). Histopathologic changes associated with SEOV infection were primarily found in the liver, consistent with a pathological diagnosis of a mild hepatitis. In conclusion, natural SEOV infection results in mild inflammation of the liver in the absence of clinical disease. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessArticle
Development and Characterization of a Sin Nombre Virus Transmission Model in Peromyscus maniculatus
Viruses 2019, 11(2), 183; https://doi.org/10.3390/v11020183
Received: 24 January 2019 / Revised: 12 February 2019 / Accepted: 19 February 2019 / Published: 21 February 2019
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Abstract
In North America, Sin Nombre virus (SNV) is the main cause of hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with a fatality rate of 35–40%. SNV is a zoonotic pathogen carried by deer mice (Peromyscus maniculatus), and few studies have [...] Read more.
In North America, Sin Nombre virus (SNV) is the main cause of hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with a fatality rate of 35–40%. SNV is a zoonotic pathogen carried by deer mice (Peromyscus maniculatus), and few studies have been performed examining its transmission in deer mouse populations. Studying SNV and other hantaviruses can be difficult due to the need to propagate the virus in vivo for subsequent experiments. We show that when compared with standard intramuscular infection, the intraperitoneal infection of deer mice can be as effective in producing SNV stocks with a high viral RNA copy number, and this method of infection provides a more reproducible infection model. Furthermore, the age and sex of the infected deer mice have little effect on viral replication and shedding. We also describe a reliable model of direct experimental SNV transmission. We examined the transmission of SNV between deer mice and found that direct contact between deer mice is the main driver of SNV transmission rather than exposure to contaminated excreta/secreta, which is thought to be the main driver of transmission of the virus to humans. Furthermore, increases in heat shock responses or testosterone levels in SNV-infected deer mice do not increase the replication, shedding, or rate of transmission. Here, we have demonstrated a model for the transmission of SNV between deer mice, the natural rodent reservoir for the virus. The use of this model will have important implications for further examining SNV transmission and in developing strategies for the prevention of SNV infection in deer mouse populations. Full article
(This article belongs to the Special Issue Hantaviruses)
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Review

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Open AccessReview
A Review of Hantavirus Research in Indonesia: Prevalence in Humans and Rodents, and the Discovery of Serang Virus
Viruses 2019, 11(8), 698; https://doi.org/10.3390/v11080698
Received: 29 June 2019 / Revised: 26 July 2019 / Accepted: 27 July 2019 / Published: 31 July 2019
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Abstract
Dengue and other common tropical infectious diseases of similar clinical presentation are endemic in Indonesia, which may lead to an underestimation of the prevalence of hantavirus (HTV) infection in the country. To better understand the current burden of HTV infection, this study aimed [...] Read more.
Dengue and other common tropical infectious diseases of similar clinical presentation are endemic in Indonesia, which may lead to an underestimation of the prevalence of hantavirus (HTV) infection in the country. To better understand the current burden of HTV infection, this study aimed to both identify acute HTV infection among hospitalized patients with fever and to determine the overall seroprevalence of HTV. These results were further considered within the context of previously reported HTV infection in humans and animals in Indonesia by conducting a review of published literature. As part of an observational cohort study of acute febrile illness, this sub-study retrospectively analyzed blood specimens obtained during admission, during the 2–4-week convalescent period, and three months after admission. Convalescent specimens from patients with clinical signs and symptoms of HTV infection were first screened for HTV IgG. When positive, convalescent specimens and paired acute specimens were screened for HTV IgM, and paired acute specimens were tested for HTV by Reverse Transcription Polymerase Chain Reaction (RT-PCR). A literature review of HTV in Indonesia was conducted on manuscripts manually reviewed for relevance after identification from a search using the terms “hantavirus/Seoul virus” and “Indonesia”. From patients at eight hospitals in seven provincial capitals, HTV IgG seroprevalence was 11.6% (38/327), with the highest being in Denpasar (16.3%, 7/43) and the lowest being in Yogyakarta (3.4%, 1/31). Anti-HTV IgG was most prevalent in adults (13.5%, 33/244) and males (15.6%, 29/186). Acute HTV infections were identified in two subjects, both of whom had Seoul virus. In Indonesia, HTVs have been studied in humans and animals since 1984. Over the past 35 years, the reported seroprevalences in rodents ranged from 0% to 34%, and in humans from 0% to 13%. Fourteen acute infections have been reported, including one in a tourist returning to Germany, but only two have been confirmed by RT-PCR. Almost all rodent and human surveillance results demonstrated serological and molecular evidence of Seoul virus infection. However, in Semarang, anti-Puumala virus IgM has been detected in humans and Puumala RNA in one rodent. In Serang, a new virus named Serang virus was identified due to its differences from Seoul virus. In Maumere, HTV and Leptospira spp. were identified simultaneously in rodents. The burden of HTV infection in Indonesia is underestimated, and additional studies are needed to understand the true prevalence. Seroprevalence data reported here, previous observations of HTV co-infections in rodents, and the prevalence of rodent-borne bacterial infections in Indonesia suggest that the population may be routinely encountering HTVs. While Seoul virus appears to be the most prevalent HTV in the country, further studies are needed to understand which HTVs are circulating. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessReview
The Needs for Developing Experiments on Reservoirs in Hantavirus Research: Accomplishments, Challenges and Promises for the Future
Viruses 2019, 11(7), 664; https://doi.org/10.3390/v11070664
Received: 27 June 2019 / Revised: 9 July 2019 / Accepted: 18 July 2019 / Published: 19 July 2019
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Abstract
Due to their large geographic distribution and potential high mortality rates in human infections, hantaviruses constitute a worldwide threat to public health. As such, they have been the subject of a large array of clinical, virological and eco-evolutionary studies. Many experiments have been [...] Read more.
Due to their large geographic distribution and potential high mortality rates in human infections, hantaviruses constitute a worldwide threat to public health. As such, they have been the subject of a large array of clinical, virological and eco-evolutionary studies. Many experiments have been conducted in vitro or on animal models to identify the mechanisms leading to pathogenesis in humans and to develop treatments of hantavirus diseases. Experimental research has also been dedicated to the understanding of the relationship between hantaviruses and their reservoirs. However, these studies remain too scarce considering the diversity of hantavirus/reservoir pairs identified, and the wide range of issues that need to be addressed. In this review, we present a synthesis of the experimental studies that have been conducted on hantaviruses and their reservoirs. We aim at summarizing the knowledge gathered from this research, and to emphasize the gaps that need to be filled. Despite the many difficulties encountered to carry hantavirus experiments, we advocate for the need of such studies in the future, at the interface of evolutionary ecology and virology. They are critical to address emerging areas of research, including hantavirus evolution and the epidemiological consequences of individual variation in infection outcomes. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessReview
Wild Rats, Laboratory Rats, Pet Rats: Global Seoul Hantavirus Disease Revisited
Viruses 2019, 11(7), 652; https://doi.org/10.3390/v11070652
Received: 31 May 2019 / Revised: 28 June 2019 / Accepted: 9 July 2019 / Published: 17 July 2019
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Abstract
Recent reports from Europe and the USA described Seoul orthohantavirus infection in pet rats and their breeders/owners, suggesting the potential emergence of a “new” public health problem. Wild and laboratory rat-induced Seoul infections have, however, been described since the early eighties, due to [...] Read more.
Recent reports from Europe and the USA described Seoul orthohantavirus infection in pet rats and their breeders/owners, suggesting the potential emergence of a “new” public health problem. Wild and laboratory rat-induced Seoul infections have, however, been described since the early eighties, due to the omnipresence of the rodent reservoir, the brown rat Rattus norvegicus. Recent studies showed no fundamental differences between the pathogenicity and phylogeny of pet rat-induced Seoul orthohantaviruses and their formerly described wild or laboratory rat counterparts. The paucity of diagnosed Seoul virus-induced disease in the West is in striking contrast to the thousands of cases recorded since the 1980s in the Far East, particularly in China. This review of four continents (Asia, Europe, America, and Africa) puts this “emerging infection” into a historical perspective, concluding there is an urgent need for greater medical awareness of Seoul virus-induced human pathology in many parts of the world. Given the mostly milder and atypical clinical presentation, sometimes even with preserved normal kidney function, the importance of simple but repeated urine examination is stressed, since initial but transient proteinuria and microhematuria are rarely lacking. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessReview
Progress on the Prevention and Treatment of Hantavirus Disease
Viruses 2019, 11(7), 610; https://doi.org/10.3390/v11070610
Received: 1 June 2019 / Revised: 28 June 2019 / Accepted: 29 June 2019 / Published: 4 July 2019
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Abstract
Hantaviruses, members of the order Bunyavirales, family Hantaviridae, have a world-wide distribution and are responsible for greater than 150,000 cases of disease per year. The spectrum of disease associated with hantavirus infection include hemorrhagic fever with renal syndrome (HFRS) and hantavirus [...] Read more.
Hantaviruses, members of the order Bunyavirales, family Hantaviridae, have a world-wide distribution and are responsible for greater than 150,000 cases of disease per year. The spectrum of disease associated with hantavirus infection include hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) also known as hantavirus cardiopulmonary syndrome (HCPS). There are currently no FDA-approved vaccines or treatments for these hantavirus diseases. This review provides a summary of the status of vaccine and antiviral treatment efforts including those tested in animal models or human clinical trials. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessReview
Hypopituitarism after Orthohantavirus Infection: What is Currently Known?
Viruses 2019, 11(4), 340; https://doi.org/10.3390/v11040340
Received: 19 March 2019 / Revised: 3 April 2019 / Accepted: 6 April 2019 / Published: 10 April 2019
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Abstract
Several case reports have described hypopituitarism following orthohantavirus infection, mostly following Puumala virus. The pathogenesis of this seemingly rare complication of orthohantavirus infection remains unknown. This review explores the possible pathophysiological mechanisms of pituitary damage due to orthohantavirus infection. In only three out [...] Read more.
Several case reports have described hypopituitarism following orthohantavirus infection, mostly following Puumala virus. The pathogenesis of this seemingly rare complication of orthohantavirus infection remains unknown. This review explores the possible pathophysiological mechanisms of pituitary damage due to orthohantavirus infection. In only three out of the 28 reported cases, hypopituitarism was detected during active infection. In the remaining cases, detection of pituitary damage was delayed, varying from two months up to thirteen months post-infection. In these cases, hypopituitarism remained undetected during the acute phase of infection or only occurred weeks to months post infection. Both ischemic and hemorrhagic damage of the pituitary gland have been detected in radiographic imaging and post-mortem studies in the studied case reports series. Ischemic damage could be caused by hypotension and/or vasospasms during the acute phase of hemorrhagic fever with renal syndrome (HFRS) while hemorrhage could be caused by thrombocytopenia, thrombopathy, and other known causes of coagulation disorders during orthohantavirus infection. Also, hypophysitis due to the presence of auto-antibodies have been suggested in the literature. In conclusion, a significant number of case reports and series describe hypopituitarism after orthohantavirus infection. In most cases hypopituitarism was diagnosed with a delay and therefore could very well be underreported. Clinicians should be aware of this potential endocrine complication, with substantial morbidity, and if unrecognized, significant mortality. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessTechnical Note
Fast, Sensitive and Specific Detection of Thailand orthohantavirus and its Variants Using One-Step Real-Time Reverse-Transcription Polymerase Chain Reaction Assay
Viruses 2019, 11(8), 718; https://doi.org/10.3390/v11080718
Received: 28 May 2019 / Revised: 15 July 2019 / Accepted: 19 July 2019 / Published: 6 August 2019
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Abstract
Genetic variants of Thailand orthohantavirus (THAIV) have been recently reported from rodents in South-East Asia and in islands from the South-West part of the Indian Ocean. In order to detect THAIV and its variants, we developed a sensitive and specific real-time RT-PCR targeting [...] Read more.
Genetic variants of Thailand orthohantavirus (THAIV) have been recently reported from rodents in South-East Asia and in islands from the South-West part of the Indian Ocean. In order to detect THAIV and its variants, we developed a sensitive and specific real-time RT-PCR targeting the S segment. Our assay was developed in two different RT-PCR systems that gave similar results in terms of sensitivity. Moreover, our results demonstrated a specificity of 100%. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessCase Report
Cytokine Storm Combined with Humoral Immune Response Defect in Fatal Hemorrhagic Fever with Renal Syndrome Case, Tatarstan, Russia
Viruses 2019, 11(7), 601; https://doi.org/10.3390/v11070601
Received: 28 May 2019 / Revised: 28 June 2019 / Accepted: 29 June 2019 / Published: 2 July 2019
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Abstract
Hemorrhagic fever with renal syndrome (HFRS) is endemic in Tatarstan, where thousands of cases are registered annually. Puumala orthohantavirus is commonly detected in human case samples as well as in captured bank voles, the rodent hosts. The pathogenesis of HFRS is still not [...] Read more.
Hemorrhagic fever with renal syndrome (HFRS) is endemic in Tatarstan, where thousands of cases are registered annually. Puumala orthohantavirus is commonly detected in human case samples as well as in captured bank voles, the rodent hosts. The pathogenesis of HFRS is still not well described, although the cytokine storm hypothesis is largely accepted. In this study, we present a comprehensive analysis of a fatal HFRS case compared with twenty four non-fatal cases where activation of the humoral and cellular immune responses, pro-inflammatory cytokines and disturbed blood coagulation were detected using immunological, histological, genetic and clinical approaches. Multiple organ failure combined with disseminated intravascular coagulation syndrome and acute renal failure was the cause of death. Decreased Interleukin (IL)-7 and increased IL-18, chemokine (C-C motif) ligand (CCL)-5, stem cell growth factor (SCGF)-b and tumor necrosis factor-beta (TNF-β) serum levels were found, supporting the cytokine storm hypothesis of hantavirus pathogenesis. Full article
(This article belongs to the Special Issue Hantaviruses)
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