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Special Issue "Hantaviruses"

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

Deadline for manuscript submissions: closed (30 November 2013)

Special Issue Editors

Guest Editor
Dr. Heinz Feldmann

Chief, Laboratory of Virology, NIAID, Building 28, Room 2A100A 903 4th Street Hamilton, MT 59840, USA
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Phone: +1-406-375-7410
Guest Editor
Dr. David Safronetz

Laboratory of Virology, NIAID, Building 28, Room 2A100A 903 4th Street Hamilton, MT 59840, USA
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Special Issue Information

Dear Colleagues,

The genus hantavirus is comprised of a unique group of viruses within the Bunyaviridae which are maintained in nature and transmitted to humans via small vertebrates, predominantly rodents. In humans hantaviruses, including Hantaan, Dobrava, Puumala, Sin Nombre and Andes viruses, are responsible for two diseases; hemorrhagic fever with renal syndrome (HFRS) and the more recently recognized hantavirus pulmonary syndrome (HPS). Combined hantaviruses have a world-wide distribution with HFRS primarily occurring in Europe and Asia with an incidence of greater than 100,000 cases annually and mortality rates of up to 15%, and HPS documented throughout the America’s with mortality rates often exceeding 30%. Despite the significant morbidity and mortality associated with this group of pathogens vaccines, antivirals and therapeutics are largely non-existent. The past several years has seen renewed research interest on several aspects of hantaviruses. The present Special Issue covers recent developments in hantavirus biology, including ecology, clinical presentation and diagnostic approaches, molecular pathogenesis, mechanisms of virus-host cell interaction, disease modeling and the development of novel therapeutic strategies against these important pathogens.

Dr. Heinz Feldmann
Dr. David Safronetz
Guest Editors

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Keywords

  • hantavirus
  • emerging viruses
  • hantavirus pulmonary syndrome
  • hemorrhagic fever with renal syndrome

Published Papers (27 papers)

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Research

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Open AccessArticle Identification of FactorsInfluencing the Puumala Virus Seroprevalence within Its Reservoir in aMontane Forest Environment
Viruses 2014, 6(10), 3944-3967; doi:10.3390/v6103944
Received: 20 May 2014 / Revised: 3 September 2014 / Accepted: 29 September 2014 / Published: 23 October 2014
Cited by 2 | PDF Full-text (871 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Puumala virus (PUUV) is a major cause of mild to moderate haemorrhagic fever with renal syndrome and is transmitted by the bank vole (Myodes glareolus). There has been a high cumulative incidence of recorded human cases in South-eastern Germany since 2004
[...] Read more.
Puumala virus (PUUV) is a major cause of mild to moderate haemorrhagic fever with renal syndrome and is transmitted by the bank vole (Myodes glareolus). There has been a high cumulative incidence of recorded human cases in South-eastern Germany since 2004 when the region was first recognized as being endemic for PUUV. As the area is well known for outdoor recreation and the Bavarian Forest National Park (BFNP) is located in the region, the increasing numbers of recorded cases are of concern. To understand the population and environmental effects on the seroprevalence of PUUV in bank voles we trapped small mammals at 23 sites along an elevation gradient from 317 to 1420m above sea level. Generalized linear mixed effects models(GLMEM) were used to explore associations between the seroprevalence of PUUV in bank voles and climate and biotic factors. We found that the seroprevalence of PUUV was low (6%–7%) in 2008 and 2009, and reached 29% in 2010. PUUV seroprevalence was positively associated with the local species diversity and deadwood layer, and negatively associated with mean annual temperature, mean annual solar radiation, and herb layer. Based on these findings, an illustrative risk map for PUUV seroprevalence prediction in bank voles was created for an area of the national park. The map will help when planning infrastructure in the national park (e.g., huts, shelters, and trails). Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Increased Plasma Cell-Free DNA Level during HTNV Infection: Correlation with Disease Severity and Virus Load
Viruses 2014, 6(7), 2723-2734; doi:10.3390/v6072723
Received: 29 November 2013 / Revised: 13 June 2014 / Accepted: 29 June 2014 / Published: 15 July 2014
Cited by 6 | PDF Full-text (1930 KB) | HTML Full-text | XML Full-text
Abstract
Cell-free DNA (cf-DNA) in blood represents a promising DNA damage response triggered by virus infection or trauma, tumor, etc. Hantavirus primarily causes two diseases: haemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS), depending on different Hantavirus species. The aim of
[...] Read more.
Cell-free DNA (cf-DNA) in blood represents a promising DNA damage response triggered by virus infection or trauma, tumor, etc. Hantavirus primarily causes two diseases: haemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS), depending on different Hantavirus species. The aim of this study was to evaluate plasma cf-DNA levels in acute phase of HFRS, and to correlate plasma cf-DNA with disease severity and plasma Hanttan virus (HTNV) load. We observed the appearance of cf-DNA in 166 plasma samples from 76 HFRS patients: the plasma cf-DNA levels peaked at the hypotensive stage of HFRS, and then decreased gradually. Until the diuretic stage, there was no significant difference in plasma cf-DNA level between patients and the healthy control. Exclusively in the febrile/hypotensive stage, the plasma cf-DNA levels of severe/critical patients were higher than those of the mild/moderate group. Moreover, the plasma cf-DNA value in the early stage of HFRS was correlated with HTNV load and disease severity. In most of the patients, plasma cf-DNA displayed a low-molecular weight appearance, corresponding to the size of apoptotic DNA. In conclusion, the plasma cf-DNA levels were dynamically elevated during HFRS, and correlated with disease severity, which suggests that plasma cf-DNA may be a potential biomarker for the pathogenesis and prognosis of HFRS. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessCommunication Muju Virus, Harbored by Myodes regulus in Korea, Might Represent a Genetic Variant of Puumala Virus, the Prototype Arvicolid Rodent-Borne Hantavirus
Viruses 2014, 6(4), 1701-1714; doi:10.3390/v6041701
Received: 9 December 2013 / Revised: 20 March 2014 / Accepted: 21 March 2014 / Published: 14 April 2014
Cited by 7 | PDF Full-text (1041 KB) | HTML Full-text | XML Full-text
Abstract
The genome of Muju virus (MUJV), identified originally in the royal vole (Myodes regulus) in Korea, was fully sequenced to ascertain its genetic and phylogenetic relationship with Puumala virus (PUUV), harbored by the bank vole (My. glareolus), and a
[...] Read more.
The genome of Muju virus (MUJV), identified originally in the royal vole (Myodes regulus) in Korea, was fully sequenced to ascertain its genetic and phylogenetic relationship with Puumala virus (PUUV), harbored by the bank vole (My. glareolus), and a PUUV-like virus, named Hokkaido virus (HOKV), in the grey red-backed vole (My. rufocanus) in Japan. Whole genome sequence analysis of the 6544-nucleotide large (L), 3652-nucleotide medium (M) and 1831-nucleotide small (S) segments of MUJV, as well as the amino acid sequences of their gene products, indicated that MUJV strains from different capture sites might represent genetic variants of PUUV, the prototype arvicolid rodent-borne hantavirus in Europe. Distinct geographic-specific clustering of MUJV was found in different provinces in Korea, and phylogenetic analyses revealed that MUJV and HOKV share a common ancestry with PUUV. A better understanding of the taxonomic classification and pathogenic potential of MUJV must await its isolation in cell culture. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Equilibrium and Kinetics of Sin Nombre Hantavirus Binding at DAF/CD55 Functionalized Bead Surfaces
Viruses 2014, 6(3), 1091-1111; doi:10.3390/v6031091
Received: 30 November 2013 / Revised: 13 February 2014 / Accepted: 23 February 2014 / Published: 10 March 2014
Cited by 5 | PDF Full-text (1742 KB) | HTML Full-text | XML Full-text | Correction
Abstract
Decay accelerating factor (DAF/CD55) is targeted by many pathogens for cell entry. It has been implicated as a co-receptor for hantaviruses. To examine the binding of hantaviruses to DAF, we describe the use of Protein G beads for binding human IgG Fc domain-functionalized
[...] Read more.
Decay accelerating factor (DAF/CD55) is targeted by many pathogens for cell entry. It has been implicated as a co-receptor for hantaviruses. To examine the binding of hantaviruses to DAF, we describe the use of Protein G beads for binding human IgG Fc domain-functionalized DAF ((DAF)2-Fc). When mixed with Protein G beads the resulting DAF beads can be used as a generalizable platform for measuring kinetic and equilibrium binding constants of DAF binding targets. The hantavirus interaction has high affinity (24–30 nM; kon ~ 105 M−1s−1, koff ~ 0.0045 s−1). The bivalent (DAF)2-Fc/SNV data agree with hantavirus binding to DAF expressed on Tanoue B cells (Kd = 14.0 nM). Monovalent affinity interaction between SNV and recombinant DAF of 58.0 nM is determined from competition binding. This study serves a dual purpose of presenting a convenient and quantitative approach of measuring binding affinities between DAF and the many cognate viral and bacterial ligands and providing new data on the binding constant of DAF and Sin Nombre hantavirus. Knowledge of the equilibrium binding constant allows for the determination of the relative fractions of bound and free virus particles in cell entry assays. This is important for drug discovery assays for cell entry inhibitors. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Changes in Diversification Patterns and Signatures of Selection during the Evolution of Murinae-Associated Hantaviruses
Viruses 2014, 6(3), 1112-1134; doi:10.3390/v6031112
Received: 29 November 2013 / Revised: 19 February 2014 / Accepted: 24 February 2014 / Published: 10 March 2014
Cited by 5 | PDF Full-text (1005 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the last 50 years, hantaviruses have significantly affected public health worldwide, but the exact extent of the distribution of hantavirus diseases, species and lineages and the risk of their emergence into new geographic areas are still poorly known. In particular, the determinants
[...] Read more.
In the last 50 years, hantaviruses have significantly affected public health worldwide, but the exact extent of the distribution of hantavirus diseases, species and lineages and the risk of their emergence into new geographic areas are still poorly known. In particular, the determinants of molecular evolution of hantaviruses circulating in different geographical areas or different host species are poorly documented. Yet, this understanding is essential for the establishment of more accurate scenarios of hantavirus emergence under different climatic and environmental constraints. In this study, we focused on Murinae-associated hantaviruses (mainly Seoul Dobrava and Hantaan virus) using sequences available in GenBank and conducted several complementary phylogenetic inferences. We sought for signatures of selection and changes in patterns and rates of diversification in order to characterize hantaviruses’ molecular evolution at different geographical scales (global and local). We then investigated whether these events were localized in particular geographic areas. Our phylogenetic analyses supported the assumption that RNA virus molecular variations were under strong evolutionary constraints and revealed changes in patterns of diversification during the evolutionary history of hantaviruses. These analyses provide new knowledge on the molecular evolution of hantaviruses at different scales of time and space. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Hantavirus Public Health Outreach Effectiveness in Three Populations: An Overview of Northwestern New Mexico, Los Santos Panama, and Region IX Chile
Viruses 2014, 6(3), 986-1003; doi:10.3390/v6030986
Received: 9 December 2013 / Revised: 13 January 2014 / Accepted: 18 February 2014 / Published: 27 February 2014
Cited by 2 | PDF Full-text (623 KB) | HTML Full-text | XML Full-text
Abstract
This research compared the effectiveness of Hantavirus Pulmonary Syndrome (HPS) outreach programs in New Mexico, Panama, and Chile. Understanding the role of human demographics, disease ecology, and human behavior in the disease process is critical to the examination of community responses in terms
[...] Read more.
This research compared the effectiveness of Hantavirus Pulmonary Syndrome (HPS) outreach programs in New Mexico, Panama, and Chile. Understanding the role of human demographics, disease ecology, and human behavior in the disease process is critical to the examination of community responses in terms of behavior changes. Attitudes, knowledge, and behavior across three populations were measured through the implementation of a self-administered questionnaire (N = 601). Surveys implemented in Chile and Panama in 2004, followed by northwestern New Mexico in 2008, attempted to assess knowledge and behavior change with respect to hantavirus in high- and lower-risk prevalence areas during endemic periods. While levels of concern over contracting hantavirus were lowest in New Mexico, they were highest in Panama. Respondents in Chile showed mid-level concern and exhibited a tendency to practice proper cleaning methods more than in New Mexico and Panama. This indicates that public health messages appear to be more effective in Chile. However, since negative behavior changes, such as sweeping and vacuuming, occur at some level in all three populations, improved messages should help decrease risk of exposure to HPS. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle The Use of Chimeric Virus-like Particles Harbouring a Segment of Hantavirus Gc Glycoprotein to Generate a Broadly-Reactive Hantavirus-Specific Monoclonal Antibody
Viruses 2014, 6(2), 640-660; doi:10.3390/v6020640
Received: 21 November 2013 / Revised: 7 January 2014 / Accepted: 18 January 2014 / Published: 7 February 2014
Cited by 2 | PDF Full-text (2408 KB) | HTML Full-text | XML Full-text
Abstract
Monoclonal antibodies (MAbs) against viral glycoproteins have important diagnostic and therapeutic applications. In most cases, the MAbs specific to viral glycoproteins are raised against intact virus particles. The biosynthesis of viral glycoproteins in heterologous expression systems such as bacteria, yeast, insect or mammalian
[...] Read more.
Monoclonal antibodies (MAbs) against viral glycoproteins have important diagnostic and therapeutic applications. In most cases, the MAbs specific to viral glycoproteins are raised against intact virus particles. The biosynthesis of viral glycoproteins in heterologous expression systems such as bacteria, yeast, insect or mammalian cells is often problematic due to their low expression level, improper folding and limited stability. To generate MAbs against hantavirus glycoprotein Gc, we have used initially a recombinant yeast-expressed full-length Puumala virus (PUUV) Gc protein. However, this approach was unsuccessful. As an alternative recombinant antigen, chimeric virus-like particles (VLPs) harboring a segment of PUUV Gc glycoprotein were generated in yeast Saccharomyces cerevisiae. A 99 amino acid (aa)-long segment of Gc protein was inserted into the major capsid protein VP1 of hamster polyomavirus at previously defined positions: either site #1 (aa 80–89) or site #4 (aa 280–289). The chimeric proteins were found to self-assemble to VLPs as evidenced by electron microscopy. Chimeric VLPs induced an efficient insert-specific antibody response in immunized mice. Monoclonal antibody (clone #10B8) of IgG isotype specific to hantavirus Gc glycoprotein was generated. It recognized recombinant full-length PUUV Gc glycoprotein both in ELISA and Western blot assay and reacted specifically with hantavirus-infected cells in immunofluorescence assay. Epitope mapping studies revealed the N-terminally located epitope highly conserved among different hantavirus strains. In conclusion, our approach to use chimeric VLPs was proven useful for the generation of virus-reactive MAb against hantavirus Gc glycoprotein. The generated broadly-reactive MAb #10B8 might be useful for various diagnostic applications. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Prevalence of Antibodies against Hantaviruses in Serum and Saliva of Adults Living or Working on Farms in Yorkshire, United Kingdom
Viruses 2014, 6(2), 524-534; doi:10.3390/v6020524
Received: 2 December 2013 / Revised: 23 January 2014 / Accepted: 25 January 2014 / Published: 5 February 2014
Cited by 3 | PDF Full-text (1167 KB) | HTML Full-text | XML Full-text
Abstract
Hantaviruses are an established cause of haemorrhagic fever with renal syndrome (HFRS) in Europe. Following a confirmed case of HFRS in the UK, in an individual residing on a farm in North Yorkshire and the Humber, a tidal estuary on the east coast
[...] Read more.
Hantaviruses are an established cause of haemorrhagic fever with renal syndrome (HFRS) in Europe. Following a confirmed case of HFRS in the UK, in an individual residing on a farm in North Yorkshire and the Humber, a tidal estuary on the east coast of Northern England, and the subsequent isolation of a Seoul hantavirus from rats trapped on the patient’s farm, it was considered appropriate to further investigate the public health risk of this virus in the region. Of a total 119 individuals tested, nine (7.6%) were seropositive for hantavirus antibodies. Seven of the seropositive samples showed a stronger reaction to Seoul and Hantaan compared to other clinically relevant hantaviruses. Observation of rodents during the day, in particular mice, was associated with a reduced risk of seropositivity. In addition to one region known to be at risk following an acute case, five further potential risk areas have been identified. This study supports recently published evidence that hantaviruses are likely to be of public health interest in the region. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters
Viruses 2014, 6(2), 516-523; doi:10.3390/v6020516
Received: 11 December 2013 / Revised: 20 January 2014 / Accepted: 22 January 2014 / Published: 31 January 2014
Cited by 3 | PDF Full-text (413 KB) | HTML Full-text | XML Full-text
Abstract
Andes virus (ANDV) is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has
[...] Read more.
Andes virus (ANDV) is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV)-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G). This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure), and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025), but animals were not significantly protected following 1 year of vaccination (p = 0.090). The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Analysis of an Outbreak of Hemorrhagic Fever with Renal Syndrome in College Students in Xi’an, China
Viruses 2014, 6(2), 507-515; doi:10.3390/v6020507
Received: 5 December 2013 / Revised: 20 January 2014 / Accepted: 26 January 2014 / Published: 29 January 2014
Cited by 7 | PDF Full-text (501 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the present study was to analyze an outbreak of hemorrhagic fever with renal syndrome (HFRS), caused by a Hantavirus, in college students in the northern urban area of Xi’an in 2012. The outbreak affected six students and included two deaths.
[...] Read more.
The aim of the present study was to analyze an outbreak of hemorrhagic fever with renal syndrome (HFRS), caused by a Hantavirus, in college students in the northern urban area of Xi’an in 2012. The outbreak affected six students and included two deaths. The epidemiological survey revealed that both of the deceased cases were misdiagnosed initially, and treatment was delayed. Furthermore, a higher rodent population density and lower HFRS vaccine coverage were observed in the affected area, which indicates a possible role in the outbreak. Rattus norvegicus (Rn) and Mus musculus (Mm) were the predominant host populations in the area. Genotyping revealed that all HVs from patients and rodents were Hantaan virus (HTNV). Sequence analysis of the S segments revealed that the HTNVs reported in this study had high similarity with strains reported in 2011 and 1985, but these viruses diverged from a strain isolated in 1984 and the HTNV prototype strain 76-118. Detection of anti-HV IgG and amplification of the S segment of HTNV from a non-natural HTNV reservoir indicates that further investigations by increased rodent trapping are necessary. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Estimating Hantavirus Risk in Southern Argentina: A GIS-Based Approach Combining Human Cases and Host Distribution
Viruses 2014, 6(1), 201-222; doi:10.3390/v6010201
Received: 30 October 2013 / Revised: 17 December 2013 / Accepted: 18 December 2013 / Published: 14 January 2014
PDF Full-text (912 KB) | HTML Full-text | XML Full-text
Abstract
We use a Species Distribution Modeling (SDM) approach along with Geographic Information Systems (GIS) techniques to examine the potential distribution of hantavirus pulmonary syndrome (HPS) caused by Andes virus (ANDV) in southern Argentina and, more precisely, define and estimate the area with the
[...] Read more.
We use a Species Distribution Modeling (SDM) approach along with Geographic Information Systems (GIS) techniques to examine the potential distribution of hantavirus pulmonary syndrome (HPS) caused by Andes virus (ANDV) in southern Argentina and, more precisely, define and estimate the area with the highest infection probability for humans, through the combination with the distribution map for the competent rodent host (Oligoryzomys longicaudatus). Sites with confirmed cases of HPS in the period 1995–2009 were mostly concentrated in a narrow strip (~90 km × 900 km) along the Andes range from northern Neuquén to central Chubut province. This area is characterized by high mean annual precipitation (~1,000 mm on average), but dry summers (less than 100 mm), very low percentages of bare soil (~10% on average) and low temperatures in the coldest month (minimum average temperature −1.5 °C), as compared to the HPS-free areas, features that coincide with sub-Antarctic forests and shrublands (especially those dominated by the invasive plant Rosa rubiginosa), where rodent host abundances and ANDV prevalences are known to be the highest. Through the combination of predictive distribution maps of the reservoir host and disease cases, we found that the area with the highest probability for HPS to occur overlaps only 28% with the most suitable habitat for O. longicaudatus. With this approach, we made a step forward in the understanding of the risk factors that need to be considered in the forecasting and mapping of risk at the regional/national scale. We propose the implementation and use of thematic maps, such as the one built here, as a basic tool allowing public health authorities to focus surveillance efforts and normally scarce resources for prevention and control actions in vast areas like southern Argentina. Full article
(This article belongs to the Special Issue Hantaviruses)
Figures

Open AccessArticle Phylogeographic Diversity of Pathogenic and Non-Pathogenic Hantaviruses in Slovenia
Viruses 2013, 5(12), 3071-3087; doi:10.3390/v5123071
Received: 30 October 2013 / Revised: 28 November 2013 / Accepted: 2 December 2013 / Published: 10 December 2013
Cited by 6 | PDF Full-text (1245 KB) | HTML Full-text | XML Full-text
Abstract
Slovenia is a very diverse country from a natural geography point of view, with many different habitats within a relatively small area, in addition to major geological and climatic differences. It is therefore not surprising that several small mammal species have been confirmed
[...] Read more.
Slovenia is a very diverse country from a natural geography point of view, with many different habitats within a relatively small area, in addition to major geological and climatic differences. It is therefore not surprising that several small mammal species have been confirmed to harbour hantaviruses: A. flavicollis (Dobrava virus), A. agrarius (Dobrava virus–Kurkino), M. glareolus (Puumala virus), S. areanus (Seewis virus),M. agrestis, M. arvalis and M. subterraneus (Tula virus). Three of the viruses, namely the Dobrava, Dobrava–Kurkino and Puumala viruses, cause disease in humans, with significant differences in the severity of symptoms. Due to changes in haemorrhagic fever with renal syndrome cases (HFRS) epidemiology, a detailed study on phylogenetic diversity and molecular epidemiology of pathogenic and non-pathogenic hantaviruses circulating in ecologically diverse endemic regions was performed. The study presents one of the largest collections of hantavirus L, M and S sequences obtained from hosts and patients within a single country. Several genetic lineages were determined for each hantavirus species, with higher diversity among non-pathogenic compared to pathogenic viruses. For pathogenic hantaviruses, a significant geographic clustering of human- and rodent-derived sequences was confirmed. Several geographic and ecological factors were recognized as influencing and limiting the formation of endemic areas. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Vascular Endothelial Growth Factor Levels in Dobrava/Belgrade Virus Infections
Viruses 2013, 5(12), 3109-3118; doi:10.3390/v5123109
Received: 16 October 2013 / Revised: 2 December 2013 / Accepted: 3 December 2013 / Published: 10 December 2013
Cited by 6 | PDF Full-text (213 KB) | HTML Full-text | XML Full-text
Abstract
The levels of vascular endothelial growth factor-A (VEGF) were estimated in 102 serum samples from 63 hospitalized Greek patients with hemorrhagic fever with renal syndrome (HFRS) caused by Dobrava/Belgrade virus. Significantly higher VEGF levels were seen in the severe when compared with non-severe
[...] Read more.
The levels of vascular endothelial growth factor-A (VEGF) were estimated in 102 serum samples from 63 hospitalized Greek patients with hemorrhagic fever with renal syndrome (HFRS) caused by Dobrava/Belgrade virus. Significantly higher VEGF levels were seen in the severe when compared with non-severe cases (mean values 851.96 pg/mL and 326.75 pg/mL, respectively; p = 0.003), while a significant difference was observed among groups based on the day after the onset of illness. In both severe and non-severe cases, VEGF peaked in the second week of illness; however, elevation of VEGF in the severe cases started later and remained high until convalescence, suggesting that the role of VEGF was associated with repair of vascular damage rather than with increased permeability. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Ribavirin Protects Syrian Hamsters against Lethal Hantavirus Pulmonary Syndrome — After Intranasal Exposure to Andes Virus
Viruses 2013, 5(11), 2704-2720; doi:10.3390/v5112704
Received: 5 September 2013 / Revised: 23 October 2013 / Accepted: 31 October 2013 / Published: 8 November 2013
Cited by 8 | PDF Full-text (871 KB) | HTML Full-text | XML Full-text
Abstract
Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS) upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of
[...] Read more.
Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS) upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of ribavirin in vitro and in an animal model. In vitro assays confirmed antiviral activity and determined that the most effective doses were 40 µg/mL and above. We tested three different concentrations of ribavirin for their capability to prevent HPS in the ANDV hamster model following an intranasal challenge. While the highest level of ribavirin (200 mg/kg) was toxic to the hamster, both the middle (100 mg/kg) and the lowest concentration (50 mg/kg) prevented HPS in hamsters without toxicity. Specifically, 8 of 8 hamsters survived intranasal challenge for both of those groups whereas 7 of 8 PBS control-treated animals developed lethal HPS. Further, we report that administration of ribavirin at 50 mg/kg/day starting on days 6, 8, 10, or 12 post-infection resulted in significant protection against HPS in all groups. Administration of ribavirin at 14 days post-infection also provided a significant level of protection against lethal HPS. These data provide in vivo evidence supporting the potential use of ribavirin as a post-exposure treatment to prevent HPS after exposure by the respiratory route. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessArticle Development of a One-Step SYBR Green I Real-Time RT-PCR Assay for the Detection and Quantitation of Araraquara and Rio Mamore Hantavirus
Viruses 2013, 5(9), 2272-2281; doi:10.3390/v5092272
Received: 13 July 2013 / Revised: 10 September 2013 / Accepted: 17 September 2013 / Published: 19 September 2013
Cited by 8 | PDF Full-text (4985 KB) | HTML Full-text | XML Full-text
Abstract
Hantaviruses are members of the family Bunyaviridaeandare an emergingcause of diseaseworldwidewithhighlethalityin the Americas. In Brazil, thediagnosis forhantaviruses is basedonimmunologictechniquesassociatedwithconventionalRT-PCR.Anovelone-stepSYBRGreenreal-timeRT-PCRwasdevelopedfor the detectionandquantitationofAraraquarahantavirus(ARAV)and Rio Mamore hantavirus (RIOMV). Thedetectionlimitof assay was 10copies/µLofRNA in vitro transcribed of segment S. The specificity of assay was evaluatedbymeltingcurveanalysis, which
[...] Read more.
Hantaviruses are members of the family Bunyaviridaeandare an emergingcause of diseaseworldwidewithhighlethalityin the Americas. In Brazil, thediagnosis forhantaviruses is basedonimmunologictechniquesassociatedwithconventionalRT-PCR.Anovelone-stepSYBRGreenreal-timeRT-PCRwasdevelopedfor the detectionandquantitationofAraraquarahantavirus(ARAV)and Rio Mamore hantavirus (RIOMV). Thedetectionlimitof assay was 10copies/µLofRNA in vitro transcribed of segment S. The specificity of assay was evaluatedbymeltingcurveanalysis, which showed thattheAraraquaravirusamplifiedproductgenerate dameltpeak at80.83±0.89°C without generating primer-dimersornon-specificproducts.The assay was more sensitive than conventional RT-PCR and we detected two samples undetected by conventional RT-PCR. The one-step SYBR Green real-time quantitative RT-PCR is specific, sensible and reproducible, which makes it a powerful tool in both diagnostic applications and general research of ARAVand RIOMVand possibly other Brazilian hantaviruses. Full article
(This article belongs to the Special Issue Hantaviruses)

Review

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Open AccessReview Antigenic Properties of N Protein of Hantavirus
Viruses 2014, 6(8), 3097-3109; doi:10.3390/v6083097
Received: 6 June 2014 / Revised: 21 July 2014 / Accepted: 21 July 2014 / Published: 13 August 2014
Cited by 4 | PDF Full-text (762 KB) | HTML Full-text | XML Full-text
Abstract
Hantavirus causes two important rodent-borne viral zoonoses, hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome (HPS) in North and South America. Twenty-four species that represent sero- and genotypes have been registered within the genus Hantavirus by the International Committee
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Hantavirus causes two important rodent-borne viral zoonoses, hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome (HPS) in North and South America. Twenty-four species that represent sero- and genotypes have been registered within the genus Hantavirus by the International Committee on Taxonomy of Viruses (ICTV). Among the viral proteins, nucleocapsid (N) protein possesses an immunodominant antigen. The antigenicitiy of N protein is conserved compared with that of envelope glycoproteins. Therefore, N protein has been used for serological diagnoses and seroepidemiological studies. An understanding of the antigenic properties of N protein is important for the interpretation of results from serological tests using N antigen. N protein consists of about 430 amino acids and possesses various epitopes. The N-terminal quarter of N protein bears linear and immunodominant epitopes. However, a serotype-specific and multimerization-dependent antigenic site was found in the C-terminal half of N protein. In this paper, the structure, function, and antigenicity of N protein are reviewed. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessReview Immunogenetic Factors Affecting Susceptibility of Humans and Rodents to Hantaviruses and the Clinical Course of Hantaviral Disease in Humans
Viruses 2014, 6(5), 2214-2241; doi:10.3390/v6052214
Received: 29 November 2013 / Revised: 17 March 2014 / Accepted: 16 May 2014 / Published: 26 May 2014
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Abstract
We reviewed the associations of immunity-related genes with susceptibility of humans and rodents to hantaviruses, and with severity of hantaviral diseases in humans. Several class I and class II HLA haplotypes were linked with severe or benign hantavirus infections, and these haplotypes varied
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We reviewed the associations of immunity-related genes with susceptibility of humans and rodents to hantaviruses, and with severity of hantaviral diseases in humans. Several class I and class II HLA haplotypes were linked with severe or benign hantavirus infections, and these haplotypes varied among localities and hantaviruses. The polymorphism of other immunity-related genes including the C4A gene and a high-producing genotype of TNF gene associated with severe PUUV infection. Additional genes that may contribute to disease or to PUUV infection severity include non-carriage of the interleukin-1 receptor antagonist (IL-1RA) allele 2 and IL-1β (-511) allele 2, polymorphisms of plasminogen activator inhibitor (PAI-1) and platelet GP1a. In addition, immunogenetic studies have been conducted to identify mechanisms that could be linked with the persistence/clearance of hantaviruses in reservoirs. Persistence was associated during experimental infections with an upregulation of anti-inflammatory responses. Using natural rodent population samples, polymorphisms and/or expression levels of several genes have been analyzed. These genes were selected based on the literature of rodent or human/hantavirus interactions (some Mhc class II genes, Tnf promoter, and genes encoding the proteins TLR4, TLR7, Mx2 and β3 integrin). The comparison of genetic differentiation estimated between bank vole populations sampled over Europe, at neutral and candidate genes, has allowed to evidence signatures of selection for Tnf, Mx2 and the Drb Mhc class II genes. Altogether, these results corroborated the hypothesis of an evolution of tolerance strategies in rodents. We finally discuss the importance of these results from the medical and epidemiological perspectives. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessReview Hantavirus Reservoirs: Current Status with an Emphasis on Data from Brazil
Viruses 2014, 6(5), 1929-1973; doi:10.3390/v6051929
Received: 25 November 2013 / Revised: 3 February 2014 / Accepted: 7 February 2014 / Published: 29 April 2014
Cited by 8 | PDF Full-text (1435 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Since the recognition of hantavirus as the agent responsible for haemorrhagic fever in Eurasia in the 1970s and, 20 years later, the descovery of hantavirus pulmonary syndrome in the Americas, the genus Hantavirus has been continually described throughout the World in a variety
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Since the recognition of hantavirus as the agent responsible for haemorrhagic fever in Eurasia in the 1970s and, 20 years later, the descovery of hantavirus pulmonary syndrome in the Americas, the genus Hantavirus has been continually described throughout the World in a variety of wild animals. The diversity of wild animals infected with hantaviruses has only recently come into focus as a result of expanded wildlife studies. The known reservoirs are more than 80, belonging to 51 species of rodents, 7 bats (order Chiroptera) and 20 shrews and moles (order Soricomorpha). More than 80genetically related viruses have been classified within Hantavirus genus; 25 recognized as human pathogens responsible for a large spectrum of diseases in the Old and New World. In Brazil, where the diversity of mammals and especially rodents is considered one of the largest in the world, 9 hantavirus genotypes have been identified in 12 rodent species belonging to the genus Akodon, Calomys, Holochilus, Oligoryzomys, Oxymycterus, Necromys and Rattus. Considering the increasing number of animals that have been implicated as reservoirs of different hantaviruses, the understanding of this diversity is important for evaluating the risk of distinct hantavirus species as human pathogens. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessReview Hantavirus Gn and Gc Envelope Glycoproteins: Key Structural Units for Virus Cell Entry and Virus Assembly
Viruses 2014, 6(4), 1801-1822; doi:10.3390/v6041801
Received: 3 January 2014 / Revised: 20 March 2014 / Accepted: 31 March 2014 / Published: 21 April 2014
Cited by 9 | PDF Full-text (1007 KB) | HTML Full-text | XML Full-text
Abstract
In recent years, ultrastructural studies of viral surface spikes from three different genera within the Bunyaviridae family have revealed a remarkable diversity in their spike organization. Despite this structural heterogeneity, in every case the spikes seem to be composed of heterodimers formed by
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In recent years, ultrastructural studies of viral surface spikes from three different genera within the Bunyaviridae family have revealed a remarkable diversity in their spike organization. Despite this structural heterogeneity, in every case the spikes seem to be composed of heterodimers formed by Gn and Gc envelope glycoproteins. In this review, current knowledge of the Gn and Gc structures and their functions in virus cell entry and exit is summarized. During virus cell entry, the role of Gn and Gc in receptor binding has not yet been determined. Nevertheless, biochemical studies suggest that the subsequent virus-membrane fusion activity is accomplished by Gc. Further, a class II fusion protein conformation has been predicted for Gc of hantaviruses, and novel crystallographic data confirmed such a fold for the Rift Valley fever virus (RVFV) Gc protein. During virus cell exit, the assembly of different viral components seems to be established by interaction of Gn and Gc cytoplasmic tails (CT) with internal viral ribonucleocapsids. Moreover, recent findings show that hantavirus glycoproteins accomplish important roles during virus budding since they self-assemble into virus-like particles. Collectively, these novel insights provide essential information for gaining a more detailed understanding of Gn and Gc functions in the early and late steps of the hantavirus infection cycle. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessReview Recent Evidence of Hantavirus Circulation in the American Tropic
Viruses 2014, 6(3), 1274-1293; doi:10.3390/v6031274
Received: 1 October 2013 / Revised: 14 February 2014 / Accepted: 24 February 2014 / Published: 14 March 2014
Cited by 5 | PDF Full-text (512 KB) | HTML Full-text | XML Full-text
Abstract
Hantaan virus was discovered in Korea during the 1970s while other similar viruses were later reported in Asia and Europe. There was no information about hantavirus human infection in the Americas until 1993 when an outbreak was described in the United States. This
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Hantaan virus was discovered in Korea during the 1970s while other similar viruses were later reported in Asia and Europe. There was no information about hantavirus human infection in the Americas until 1993 when an outbreak was described in the United States. This event promoted new studies to find hantaviruses in the Americas. At first, many studies were conducted in Brazil, Argentina, Chile, Uruguay and Paraguay, while other Latin American countries began to report the presence of these agents towards the end of the 20th century. More than 30 hantaviruses have been reported in the Western Hemisphere with more frequent cases registered in the southern cone (Argentina, Chile, Uruguay, Paraguay, Bolivia and Brazil). However there was an important outbreak in 2000 in Panama and some rare events have been described in Peru, Venezuela and French Guiana. Since hantaviruses have only recently emerged as a potential threat in the tropical zones of the Americas, this review compiles recent hantavirus reports in Central America, the Caribbean islands and the northern region of South America. These studies have generated the discovery of new hantaviruses and could help to anticipate the presentation of possible future outbreaks in the region. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessReview Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions
Viruses 2014, 6(3), 1317-1335; doi:10.3390/v6031317
Received: 10 January 2014 / Revised: 19 February 2014 / Accepted: 24 February 2014 / Published: 14 March 2014
Cited by 7 | PDF Full-text (715 KB) | HTML Full-text | XML Full-text
Abstract
Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a
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Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessReview More Novel Hantaviruses and Diversifying Reservoir Hosts — Time for Development of Reservoir-Derived Cell Culture Models?
Viruses 2014, 6(3), 951-967; doi:10.3390/v6030951
Received: 12 December 2013 / Revised: 11 February 2014 / Accepted: 15 February 2014 / Published: 26 February 2014
Cited by 5 | PDF Full-text (718 KB) | HTML Full-text | XML Full-text
Abstract
Due to novel, improved and high-throughput detection methods, there is a plethora of newly identified viruses within the genus Hantavirus. Furthermore, reservoir host species are increasingly recognized besides representatives of the order Rodentia, now including members of the mammalian orders Soricomorpha/Eulipotyphla and
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Due to novel, improved and high-throughput detection methods, there is a plethora of newly identified viruses within the genus Hantavirus. Furthermore, reservoir host species are increasingly recognized besides representatives of the order Rodentia, now including members of the mammalian orders Soricomorpha/Eulipotyphla and Chiroptera. Despite the great interest created by emerging zoonotic viruses, there is still a gross lack of in vitro models, which reflect the exclusive host adaptation of most zoonotic viruses. The usually narrow host range and genetic diversity of hantaviruses make them an exciting candidate for studying virus-host interactions on a cellular level. To do so, well-characterized reservoir cell lines covering a wide range of bat, insectivore and rodent species are essential. Most currently available cell culture models display a heterologous virus-host relationship and are therefore only of limited value. Here, we review the recently established approaches to generate reservoir-derived cell culture models for the in vitro study of virus-host interactions. These successfully used model systems almost exclusively originate from bats and bat-borne viruses other than hantaviruses. Therefore we propose a parallel approach for research on rodent- and insectivore-borne hantaviruses, taking the generation of novel rodent and insectivore cell lines from wildlife species into account. These cell lines would be also valuable for studies on further rodent-borne viruses, such as orthopox- and arenaviruses. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessReview Were the English Sweating Sickness and the Picardy Sweat Caused by Hantaviruses?
Viruses 2014, 6(1), 151-171; doi:10.3390/v6010151
Received: 12 October 2013 / Revised: 4 December 2013 / Accepted: 9 December 2013 / Published: 7 January 2014
Cited by 1 | PDF Full-text (262 KB) | HTML Full-text | XML Full-text
Abstract
The English sweating sickness caused five devastating epidemics between 1485 and 1551, England was hit hardest, but on one occasion also mainland Europe, with mortality rates between 30% and 50%. The Picardy sweat emerged about 150 years after the English sweat disappeared, in
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The English sweating sickness caused five devastating epidemics between 1485 and 1551, England was hit hardest, but on one occasion also mainland Europe, with mortality rates between 30% and 50%. The Picardy sweat emerged about 150 years after the English sweat disappeared, in 1718, in France. It caused 196 localized outbreaks and apparently in its turn disappeared in 1861. Both diseases have been the subject of numerous attempts to define their origin, but so far all efforts were in vain. Although both diseases occurred in different time frames and were geographically not overlapping, a common denominator could be what we know today as hantavirus infections. This review aims to shed light on the characteristics of both diseases from contemporary as well as current knowledge and suggests hantavirus infection as the most likely cause for the English sweating sickness as well as for the Picardy sweat. Full article
(This article belongs to the Special Issue Hantaviruses)

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Open AccessShort Communication Rapid Enzyme-Linked Immunosorbent Assay for the Detection of Hantavirus-Specific Antibodies in Divergent Small Mammals
Viruses 2014, 6(5), 2028-2037; doi:10.3390/v6052028
Received: 5 December 2013 / Revised: 16 April 2014 / Accepted: 20 April 2014 / Published: 6 May 2014
Cited by 2 | PDF Full-text (771 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We assessed the utility of an enzyme-linked immunosorbent assay (ELISA) for the detection of hantavirus-specific antibodies from sera of Oligoryzomys longicaudatus, the principal reservoir of Andes virus (ANDV), using an antigen previously developed for detection of antibodies to Sin Nombre virus (SNV)
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We assessed the utility of an enzyme-linked immunosorbent assay (ELISA) for the detection of hantavirus-specific antibodies from sera of Oligoryzomys longicaudatus, the principal reservoir of Andes virus (ANDV), using an antigen previously developed for detection of antibodies to Sin Nombre virus (SNV) in sera from Peromyscus maniculatus. The assay uses a protein A/G horseradish peroxidase conjugate and can be performed in as little as 1.5 hours. Serum samples from Oligoryzomys longicaudatus collected in central-south Chile were used and the assay identified several that were antibody positive. This assay can be used for the rapid detection of antibodies to divergent hantaviruses from geographically and phylogenetically distant rodent species. Full article
(This article belongs to the Special Issue Hantaviruses)
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Open AccessShort Communication Characterization of Juquitiba Virus in Oligoryzomys fornesi from Brazilian Cerrado
Viruses 2014, 6(4), 1473-1482; doi:10.3390/v6041473
Received: 15 October 2013 / Revised: 30 November 2013 / Accepted: 17 December 2013 / Published: 26 March 2014
Cited by 3 | PDF Full-text (280 KB) | HTML Full-text | XML Full-text
Abstract
The Juquitiba virus, an agent of Hantavirus Cardiopulmonary Syndrome, is one of the most widely distributed hantavirus found in South America. It has been detected in Oligoryzomys nigripes, Akodon montensis, Oxymycterus judex, Akodon paranaensis in Brazil and in O. nigripes
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The Juquitiba virus, an agent of Hantavirus Cardiopulmonary Syndrome, is one of the most widely distributed hantavirus found in South America. It has been detected in Oligoryzomys nigripes, Akodon montensis, Oxymycterus judex, Akodon paranaensis in Brazil and in O. nigripes, Oryzomys sp. and Oligoryzomys fornesi rodents in Argentine, Paraguay and Uruguay. Here, we report the genomic characterization of the complete S segment from the Juquitiba strain, isolated from the lung tissues of O. fornesi, the presumed rodent reservoir of Anajatuba virus in Brazilian Amazon, captured in the Cerrado Biome, Brazil. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessBrief Report First Molecular Evidence for Puumala Hantavirus in Poland
Viruses 2014, 6(1), 340-353; doi:10.3390/v6010340
Received: 29 November 2013 / Revised: 10 January 2014 / Accepted: 14 January 2014 / Published: 23 January 2014
Cited by 4 | PDF Full-text (634 KB) | HTML Full-text | XML Full-text
Abstract
Puumala virus (PUUV) causes mild to moderate cases of haemorrhagic fever with renal syndrome (HFRS), and is responsible for the majority of hantavirus infections of humans in Fennoscandia, Central and Western Europe. Although there are relatively many PUUV sequences available from different European
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Puumala virus (PUUV) causes mild to moderate cases of haemorrhagic fever with renal syndrome (HFRS), and is responsible for the majority of hantavirus infections of humans in Fennoscandia, Central and Western Europe. Although there are relatively many PUUV sequences available from different European countries, little is known about the presence of this virus in Poland. During population studies in 2009 a total of 45 bank voles were trapped at three sites in north-eastern Poland, namely islands on Dejguny and Dobskie Lakes and in a forest near Mikołajki. S and M segment-specific RT-PCR assays detected PUUV RNA in three animals from the Mikołajki site. The obtained partial S and M segment sequences demonstrated the highest similarity to the corresponding segments of a PUUV strain from Latvia. Analysis of chest cavity fluid samples by IgG ELISA using a yeast-expressed PUUV nucleocapsid protein resulted in the detection of two seropositive samples, both being also RT-PCR positive. Interestingly, at the trapping site in Mikołajki PUUV-positive bank voles belong to the Carpathian and Eastern genetic lineages within this species. In conclusion, we herein present the first molecular evidence for PUUV in the rodent reservoir from Poland. Full article
(This article belongs to the Special Issue Hantaviruses)
Open AccessShort Communication Increased Detection of Sin Nombre Hantavirus RNA in Antibody-Positive Deer Mice from Montana, USA: Evidence of Male Bias in RNA Viremia
Viruses 2013, 5(9), 2320-2328; doi:10.3390/v5092320
Received: 30 July 2013 / Revised: 13 September 2013 / Accepted: 19 September 2013 / Published: 24 September 2013
Cited by 4 | PDF Full-text (73 KB) | HTML Full-text | XML Full-text
Abstract
Hantaviruses are widespread emergent zoonotic agents that cause unapparent or limited disease in their rodent hosts, yet cause acute, often fatal pulmonary or renal infections in humans. Previous laboratory experiments with rodent reservoir hosts indicate that hantaviruses can be cleared from host blood
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Hantaviruses are widespread emergent zoonotic agents that cause unapparent or limited disease in their rodent hosts, yet cause acute, often fatal pulmonary or renal infections in humans. Previous laboratory experiments with rodent reservoir hosts indicate that hantaviruses can be cleared from host blood early in the infection cycle, while sequestered long term in various host organs. Field studies of North American deer mice (Peromyscus maniculatus), the natural reservoir of Sin Nombre hantavirus, have shown that viral RNA can be transiently detected well past the early acute infection stage, but only in the minority of infected mice. Here, using a non-degenerate RT-PCR assay optimized for SNV strains known to circulate in Montana, USA, we show that viral RNA can be repeatedly detected on a monthly basis in up to 75% of antibody positive deer mice for periods up to 3–6 months. More importantly, our data show that antibody positive male deer mice are more than twice as likely to have detectable SNV RNA in their blood as antibody positive females, suggesting that SNV-infected male deer mice are more likely to shed virus and for longer periods of time. Full article
(This article belongs to the Special Issue Hantaviruses)

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