Orthohantaviruses are rodent-borne emerging viruses that may cause severe diseases in humans but no apparent pathology in their small mammal reservoirs. However, the mechanisms leading to tolerance or pathogenicity in humans and persistence in rodent reservoirs are poorly understood, as is the manner in which they spread within and between organisms. Here, we used a range of cellular and molecular approaches to investigate the interactions of three different orthohantaviruses-Puumala virus (PUUV), responsible for a mild to moderate form of hemorrhagic fever with renal syndrome in humans, Tula virus (TULV) with low pathogenicity, and non-pathogenic Prospect Hill virus (PHV)-with human and rodent host cell lines. Besides the fact that cell susceptibility to virus infection was shown to depend on the cell type and virus strain, the three orthohantaviruses were able to infect Vero E6 and HuH7 human cells, but only the former secreted infectious particles. In cells derived from PUUV reservoir, the bank vole (Myodes glareolus), PUUV achieved a complete viral cycle, while TULV did not enter the cells and PHV infected them but did not produce infectious particles, reflecting differences in host specificity. A search for mature virions by electron microscopy (EM) revealed that TULV assembly occurred in part at the plasma membrane, whereas PHV particles were trapped in autophagic vacuoles in cells of the heterologous rodent host. We described differential interactions of orthohantaviruses with cellular factors, as supported by the cellular distribution of viral nucleocapsid protein with cell compartments, and proteomics identification of cellular partners. Our results also showed that interferon (IFN) dependent gene expression was regulated in a cell and virus species dependent manner. Overall, our study highlighted the complexity of the host-virus relationship and demonstrated that orthohantaviruses are restricted at different levels of the viral cycle. In addition, the study opens new avenues to further investigate how these viruses differ in their interactions with cells to evade innate immunity and how it depends on tissue type and host species.

• MeSH
• Arvicolinae MeSH
• Orthohantavirus * genetics   MeSH
• Rodentia MeSH
• Interferons MeSH
• Humans MeSH
• Nucleocapsid Proteins genetics   MeSH
• RNA Viruses * MeSH
• Puumala virus * genetics   MeSH
• Viruses * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Hantaviruses are zoonotic pathogens that can cause subclinical to lethal infections in humans. In Europe, five orthohantaviruses are present in rodents: Myodes-associated Puumala orthohantavirus (PUUV), Microtus-associated Tula orthohantavirus, Traemmersee hantavirus (TRAV)/ Tatenale hantavirus (TATV)/ Kielder hantavirus, rat-borne Seoul orthohantavirus, and Apodemus-associated Dobrava-Belgrade orthohantavirus (DOBV). Human PUUV and DOBV infections were detected previously in Lithuania, but the presence of Microtus-associated hantaviruses is not known. For this study we screened 234 Microtus voles, including root voles (Microtus oeconomus), field voles (Microtus agrestis) and common voles (Microtus arvalis) from Lithuania for hantavirus infections. This initial screening was based on reverse transcription-polymerase chain reaction (RT-PCR) targeting the S segment and serological analysis. A novel hantavirus was detected in eight of 79 root voles tentatively named "Rusne virus" according to the capture location and complete genome sequences were determined. In the coding regions of all three genome segments, Rusne virus showed high sequence similarity to TRAV and TATV and clustered with Kielder hantavirus in phylogenetic analyses of partial S and L segment sequences. Pairwise evolutionary distance analysis confirmed Rusne virus as a strain of the species TRAV/TATV. Moreover, we synthesized the entire nucleocapsid (N) protein of Rusne virus in Saccharomyces cerevisiae. We observed cross-reactivity of antibodies raised against other hantaviruses, including PUUV, with this new N protein. ELISA investigation of all 234 voles detected Rusne virus-reactive antibodies exclusively in four of 79 root voles, all being also RNA positive, but not in any other vole species. In conclusion, the detection of Rusne virus RNA in multiple root voles at the same trapping site during three years and its absence in sympatric field voles suggests root voles as the reservoir host of this novel virus. Future investigations should evaluate host association of TRAV, TATV, Kielder virus and the novel Rusne virus and their evolutionary relationships.

• MeSH
• Arvicolinae * MeSH
• Species Specificity MeSH
• Genome, Viral * MeSH
• Hantavirus Infections epidemiology   veterinary   virology   MeSH
• Orthohantavirus classification   genetics   isolation & purification   MeSH
• Rodent Diseases epidemiology   virology   MeSH
• Prevalence MeSH
• Whole Genome Sequencing MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Lithuania MeSH

Infekcie spôsobené hantavírusom sa v pediatrickej populácii vyskytujú zriedkavo, ale celosvetovo ich incidencia v ostatných rokoch narastá. V Európe je najčastejším vyvolávateľom Puumala vírus spôsobujúci ľahšiu formu hemoragickej horúčky s renálnym syndrómom, známu ako nefropatia epidemica. V úvode ochorenia dominujú febrility, cefalea, lumbalgie či bolesti brucha. Postupne dochádza k rozvoju akútneho poškodenia obličiek na podklade akútnej tubulointersticiálnej nefritídy. Špecifická liečba zatiaľ neexistuje, základom je symptomatická terapia. Väčšina pacientov sa plne vylieči, u niektorých možno sledovať reziduálne zníženú glomerulovú filtráciu, prípadne rozvoj sekundárnej hypertenzie. V príspevku uvádzame zaujímavé kazuistiky troch detí s akútnym zlyhaním obličiek vyvolaným hantavírusovou infekciou.

Infections caused by hantaviruses are rare in child patients, although their incidence has increased worldwide in last few years. In Europe is the most common representative the Puumala virus which causes nefropathia epidemica, milder form of hemorrhagic fever with renal syndrome. The disease initially manifests itself mainly by fever, cephalea, backpain or abdominal pain. Gradually acute renal injury develops due to acute tubulointerstitial nephritis. There is no specific therapy yet, the basis is still symptomatic treatment. Most patients are fully cured, some may experience residually decreased glomerular filtration or secondary hypertension. We present three cases of children with acute renal failure caused by confirmed hantavirus infection.

• MeSH
• Diagnosis, Differential MeSH
• Child MeSH
• Hantavirus Infections * diagnosis   drug therapy   pathology   MeSH
• Hemorrhagic Fever with Renal Syndrome * diagnosis   drug therapy   pathology   MeSH
• Nephritis, Interstitial diagnosis   drug therapy   MeSH
• Arthritis, Juvenile diagnosis   drug therapy   MeSH
• Comorbidity MeSH
• Humans MeSH
• Adolescent MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Case Reports MeSH
• Geographicals
• Slovakia MeSH

In 2012, Tigray orthohantavirus was discovered in Ethiopia, but its seasonal infection in small mammals, and whether it poses a risk to humans was unknown. The occurrence of small mammals, rodents and shrews, in human inhabitations in northern Ethiopia is affected by season and presence of stone bunds. We sampled small mammals in two seasons from low- and high-density stone bund fields adjacent to houses and community-protected semi-natural habitats in Atsbi and Hagere Selam, where Tigray orthohantavirus was first discovered. We collected blood samples from both small mammals and residents using filter paper. The presence of orthohantavirus-reactive antibodies in blood was then analyzed using immunofluorescence assay (human samples) and enzyme linked immunosorbent assays (small mammal samples) with Puumala orthohantavirus as antigen. Viral RNA was detected by RT-PCR using small mammal blood samples. Total orthohantavirus prevalence (antibodies or virus RNA) in the small mammals was 3.37%. The positive animals were three Stenocephalemys albipes rats (prevalence in this species = 13.04%). The low prevalence made it impossible to determine whether season and stone bunds were associated with orthohantavirus prevalence in the small mammals. In humans, we report the first detection of orthohantavirus-reactive IgG antibodies in Ethiopia (seroprevalence = 5.26%). S. albipes lives in close proximity to humans, likely increasing the risk of zoonotic transmission.

• MeSH
• Hantavirus Infections epidemiology   immunology   transmission   MeSH
• Orthohantavirus genetics   immunology   MeSH
• Immunoglobulin G blood   MeSH
• Rats MeSH
• Humans MeSH
• Rodent Diseases immunology   transmission   virology   MeSH
• Prevalence MeSH
• Antibodies, Viral blood   MeSH
• Cross-Sectional Studies MeSH
• Risk Factors MeSH
• RNA, Viral genetics   MeSH
• Rural Population MeSH
• Disease Reservoirs virology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Ethiopia MeSH

During 2008-2018, we collected samples from rodents and patients throughout the Czech Republic and characterized hantavirus isolates. We detected Dobrava-Belgrade and Puumala orthohantaviruses in patients and Dobrava-Belgrade, Tula, and Seewis orthohantaviruses in rodents. Increased knowledge of eco-epidemiology of hantaviruses will improve awareness among physicians and better outcomes of patients.

• MeSH
• Phylogeny MeSH
• Hantavirus Infections epidemiology   immunology   virology   MeSH
• Orthohantavirus genetics   immunology   MeSH
• Immunoglobulin G immunology   MeSH
• Immunoglobulin M immunology   MeSH
• Humans MeSH
• Molecular Epidemiology * MeSH
• Antibodies, Viral MeSH
• Genes, Viral MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Letter MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH

Hantaviry jsou RNA viry z čeledi Bunyaviridae. Jejich hostiteli jsou živočichové ze třídy savci, z řádu hlodavci (norníci, myšice, hraboši, potkani, křečci), hmyzožravci (rejsci, krtci) a letouni (netopýři). Hantaviry se vyskytují na mnoha místech Evropy, Ameriky, Asie a Afriky. Na území České republiky byl prokázán výskyt 5 druhů hantavirů (Dobrava/Belgrade, Puumala, Tula, Seewis a Asikkala), z nich první 3 mohou způsobit lidská onemocnění. Přestože hantavirové nákazy mohou probíhat velmi závažně, v odborné lékařské veřejnosti nejsou příliš známé a na možnost této infekce se nemyslí. V práci je popsána kazuistika hantavirové hemoragické horečky s renálním syndromem (HFRS) s fatálním zakončením. Onemocnění u tohoto pacienta probíhalo pod typickým klinickým obrazem, přesto správná diagnóza byla stanovena až post mortem.

Hantaviruses are RNA viruses of the family Bunyaviridae. Their hosts are mammals of the orders rodents (voles, rats, mice), insectivores (shrews, moles), and chiroptera (bats). Hantaviruses are present in many areas of Europe, the Americas, Asia, and Africa. In the Czech Republic, the occurrence of five species of hantaviruses has been reported (Dobrava/Belgrade, Puumala, Tula, Seewis, and Asikkala), with the first three of them causing human diseases. Although the course of hantavirus infections can be very serious, there is a low awareness of these diseases, even among health professionals, and hantavirus is often not considered in the diagnosis. A case history is reported of a patient who developed hantavirus haemorrhagic fever with renal syndrome (HFRS) with fatal outcome. The patient presented with typical clinical signs, but the correct diagnosis was only made at post mortem.

• MeSH
• Antipyretics MeSH
• Early Diagnosis MeSH
• Fatal Outcome MeSH
• Hantavirus Infections epidemiology   physiopathology   transmission   MeSH
• Orthohantavirus * classification   pathogenicity   MeSH
• Hemorrhagic Fever with Renal Syndrome * diagnosis   drug therapy   MeSH
• Urinary Tract Infections MeSH
• beta-Lactamase Inhibitors MeSH
• Amoxicillin-Potassium Clavulanate Combination therapeutic use   MeSH
• Middle Aged MeSH
• Dipyrone therapeutic use   MeSH
• Multiple Organ Failure etiology   MeSH
• Mydriasis MeSH
• Neurologic Examination MeSH
• Autopsy MeSH
• Polymerase Chain Reaction utilization   MeSH
• Shock, Septic MeSH
• Check Tag
• Middle Aged MeSH
• Male MeSH
• Publication type
• Case Reports MeSH
• Geographicals
• Czech Republic MeSH

Puumala virus (PUUV), carried by bank voles (Myodes glareolus), is the medically most important hantavirus in Central and Western Europe. In this study, a total of 523 bank voles (408 from Germany, 72 from Slovakia, and 43 from Czech Republic) collected between the years 2007-2012 were analyzed for the presence of hantavirus RNA. Partial PUUV genome segment sequences were obtained from 51 voles. Phylogenetic analyses of all three genome segments showed that the newfound strains cluster with other Central and Western European PUUV strains. The new sequences from Šumava (Bohemian Forest), Czech Republic, are most closely related to the strains from the neighboring Bavarian Forest, a known hantavirus disease outbreak region. Interestingly, the Slovak strains clustered with the sequences from Bohemian and Bavarian Forests only in the M but not S segment analyses. This well-supported topological incongruence suggests a segment reassortment event or, as we analyzed only partial sequences, homologous recombination. Our data highlight the necessity of sequencing all three hantavirus genome segments and of a broader bank vole screening not only in recognized endemic foci but also in regions with no reported human hantavirus disease cases.

• MeSH
• Arvicolinae virology   MeSH
• Phylogeny MeSH
• Genotype MeSH
• Hantavirus Infections virology   MeSH
• Orthohantavirus genetics   MeSH
• Humans MeSH
• Evolution, Molecular MeSH
• RNA, Viral genetics   MeSH
• Puumala virus genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Europe MeSH
• Germany MeSH
• Slovakia MeSH

Nejčastějším virovým onemocněním přenášeným hlodavci jsou v České republice hantavirózy s průměrnou roční incidencí 0,02 případů/100 000 obyvatel a výskytem specifických protilátek asi u 1 % obyvatel. Na našem území byli doposud popsáni 4 zástupci hantavirů (Puumala, Dobrava--Belgrade, Tula, Seewis), z nichž onemocnění u člověka prokazatelně způsobují viry Puumala (obvykle s mírnou formou onemocnění, nephropathia epidemica) a Dobrava-Belgrade (způsobující hemoragickou horečku spojenou se selháním ledvin). Cílem předkládané práce je podat nejnovější ucelený přehled pro člověka patogenních hantavirů vyskytujících se v České republice ve světle studií, které byly publikovány v posledních třiceti letech, včetně geografického rozšíření hantavirů a popisu klinických onemocnění. Nedávná detekce viru Tula u imunokompromitovaného jedince na Ostravsku nebo současné zprávy o klinických onemocněních způsobených virem Seoul v Evropě zdůrazňují problém možné emergence opomíjených hantavirových nákaz v blízké budoucnosti.

Hantavirus disease is the most common rodent-borne viral infection in the Czech Republic, with a mean annual incidence of 0.02 cases per 100 000 population and specific antibodies detected in 1% of the human population. Four hantaviruses (Puumala, Dobrava-Belgrade, Tula, and Seewis) circulate in this country, of which Puumala virus (responsible for a mild form of hemorrhagic fever with renal syndrome called nephropathia epidemica) and Dobrava-Belgrade virus (causing haemorrhagic fever with renal syndrome) have been proven to cause human disease. The aim of this study is to provide a comprehensive review of the hantaviruses occurring in the Czech Republic, based on the literature published during the past three decades, including their geographical distribution and clinical symptoms. The recent detection of Tula virus in an immunocompromised person as well as reports of Seoul virus infections in Europe highlight the possible emergence of neglected hantavirus infections in the foreseeable future.

• MeSH
• Genome, Viral MeSH
• Hantavirus Infections * diagnosis   epidemiology   classification   pathology   prevention & control   therapy   MeSH
• Orthohantavirus * genetics   classification   pathogenicity   MeSH
• Hemorrhagic Fever with Renal Syndrome diagnosis   microbiology   prevention & control   therapy   MeSH
• Rodentia MeSH
• Geography, Medical MeSH
• Humans MeSH
• Animal Diseases MeSH
• Disease Transmission, Infectious MeSH
• Vaccination MeSH
• Hantaan virus MeSH
• Puumala virus MeSH
• Zoonoses epidemiology   genetics   transmission   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Výzkum kliniky, epidemiologie, virologie a ekologie hantavirových infekcí v endemické oblasti na Šumavě. Klinická charakteristika nemocných osob, jejich diagnostika a léčení. Identifikace rizikových území s potenciálně vyšší nemocností suspektních onemocnění touto nákazou. Analýza hlášených onemocnění s možnou hantavirovou etiologií Zjištění promořenosti osob z endemické oblasti pomocí vyšetření archivovaných sér víceúčelových sérologických přehledů shromážděných v minulosti. Odchyt a vyšetření hlodavcůna přítomnost protilátek a izolaci viru. Vypracování návrhu preventivních opatření v terénu, což mj. přispěje i ke snížení profesionálního rizika osob pracujících v oblastech s přírodními ohnisky hantaviróz.; Research of clinical features, epidemiology, virology and ecology of hantavirus infections in the endemic area Sumava. Characteristics of the clinical course of the disease in infected persons, their diagnosis and treatment. Identification of risk areasreporting higher number of cases suspected of hantavirus infection. Analysis of reported cases with possible hantavirus etiology. Determination of infection rate in the population of residents living in endemic areas by examination of serum samples fromthe past serological surveys. Trapping of reservoir rodents and their examination. Development of preventive measures focused on the endemic areas with the objective to reduce occupational risk of persons working in areas with known natural foci of hantavirus infection.

• MeSH
• Hantavirus Infections epidemiology   MeSH
• Orthohantavirus isolation & purification   MeSH
• Rodentia blood   MeSH
• Incidence MeSH
• Nephritis, Interstitial MeSH
• Puumala virus MeSH
• Geographicals
• Czech Republic MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• epidemiologie
• NML Publication type
• závěrečné zprávy o řešení grantu IGA MZ ČR

Hantaviruses are RNA viruses of the Bunyaviridae family, represented in the Czech Republic by three genospecies: Dobrava-Belgrade, Puumala and Tula. They persist in natural foci of infection. In 2004 to 2009, a local outbreak with 18 reported cases of nephropathia epidemica caused by Puumala hantavirus occurred in the Šumava mountains and foothills and was spacially associated with another outbreak in Lower Bavaria, Germany. In the Jelení locality in the Šumava mountains at 880 m above sea level, we identified a natural focus of infection suspected to be the source of hantavirus infection in forest workers. The focus was characterized geobotanically as a montane mixed forest with the predominance of beeches within the association Dentario enneaphylli-Fagetum, alliance Fagion, sub-alliance Eu-Fagenion, in a cold climate region with a podzolic soil. The biocenoses where hantaviruses are circulating typically show higher microclimate humidity. Their characteristization can be helpful in predicting where hantaviruses are likely to circulate.

• Keywords
• Puumala, biocenosis, Myodes glareolus,
• MeSH
• Arvicolinae MeSH
• Ecosystem MeSH
• Disease Outbreaks MeSH
• Financing, Organized MeSH
• Orthohantavirus MeSH
• Hemorrhagic Fever with Renal Syndrome epidemiology   veterinary   MeSH
• Humans MeSH
• Rodent Diseases epidemiology   virology   MeSH
• Prevalence MeSH
• Population Surveillance MeSH
• Puumala virus isolation & purification   MeSH
• Disease Reservoirs veterinary   virology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Geographicals
• Czech Republic MeSH