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Background: Orthohantavirus hantanense (HTNV) poses a substantial global public health threat due to its role in causing hemorrhagic fever with renal syndrome (HFRS). HTNV outbreaks are particularly prevalent in the Gyeonggi and Gangwon Provinces of the Republic of Korea (ROK). This study aimed to evaluate the application of advanced nanopore sequencing and bioinformatics to generate complete genome sequences of HTNV, with the objective of accurately identifying infection sources and analyzing their genetic diversity., Methodology/principal Findings: In 2022 and 2023, we collected 579 small mammals from 11 distinct locations across Gyeonggi and Gangwon Provinces, as well as in Gwangju Metropolitan City, ROK. Among these, 498 Apodemus agrarius specimens were subjected to an epidemiological survey to investigate HTNV infections. The serological and molecular positivity of HTNV were found to be 65/498 (13.1%) and 17/65 (26.2%), respectively. Furthermore, 15 whole-genome sequences of HTNV were obtained from rodents in Gyeonggi and Gangwon Provinces. We developed a novel amplicon-based nanopore sequencing approach to acquire high-fidelity and precise genomic sequences of HTNV. Genome exchange analysis revealed three reassortant candidates, including heterogeneous L segments, from Paju-si and Yeoncheon-gun in Gyeonggi Province., Conclusion/significance: Our findings enhance the resolution of the spatiotemporal genomic surveillance of HTNV by consistently providing new viral sequences and epidemiological data from HFRS-endemic regions in the ROK. This report signifies a notable advancement in nanopore sequencing techniques and bioinformatics, offering a robust platform for genome-based diagnostics and sophisticated phylogenetic analyses of orthohantaviruses, which are essential for public health strategies aimed at controlling HFRS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

During 2020-2023, we sequenced Bayou virus from 2 patients in Louisiana, USA, with hantavirus cardiopulmonary syndrome. Direct virus sequencing demonstrated an inferred evolutionary relationship to previous cases. Our findings demonstrate that separate virus spillovers cause isolated cases and probable wide distribution of Bayou hantavirus in rodents across Louisiana.

In July 2017, an investigation into the cause of neurological signs in a black flying fox (Pteropus alecto, family Pteropodidae) identified a putative novel hantavirus (Robina virus, ROBV, order Bunyavirales, family Hantaviridae, genus Mobatvirus) in its brain. Analysis of the evolutionary relationship between other hantaviruses using maximum-likelihood, a systematic Bayesian clustering approach, and a minimum spanning tree, all suggest that ROBV is most closely related to another Mobatvirus, Quezon virus, previously identified in the lung of a Philippine frugivorous bat (Rousettus amplexicaudatus, also family Pteropodidae). Subsequently, between March 2018 and October 2023, a total of 495 bats were opportunistically screened for ROBV with an experimental qRT-PCR. The total prevalence of ROBV RNA detected in Pteropus spp. was 4.2% (95% CI 2.8-6.4%). Binomial modelling identified that there was substantial evidence supporting an increase (P = 0.033) in the detection of ROBV RNA in bats in 2019 and 2020 suggesting of a possible transient epidemic. There was also moderate evidence to support the effect of season (P = 0.064), with peak detection in the cooler seasons, autumn, and winter, possibly driven by physiological and ecological factors similar to those already identified for other bat-borne viruses. This is Australia's first reported putative hantavirus and its identification could expand the southern known range of hantaviruses in Australasia., Competing Interests: Declarations. Conflicts of interest: The authors acknowledge a working relationship with Dr Gavin Wilkie (Illumina, Inc). Research involving human and animal participants: Ethical review and approval were waived for this study due to animals being submitted to the state for disease investigations unrelated to this study., (© 2024. Crown.)

Background: Bat-borne hantaviruses have been identified worldwide but little is known about neotropical bats in the megadiverse biomes of the American continent. Although serological evidence has hinted at hantavirus circulation in Brazil, the scarce number of genomic detection represents a gap to understand viral diversity, prevalence, and ecology of bat-borne hantaviruses., Objective: We aim to investigate and evaluate the presence and prevalence of bat-borne hantavirus in the Brazilian Atlantic Forest., Methods: Here in, 97 lung and kidney tissue samples from bats captured in the Brazilian Atlantic Rainforest were submitted to hantavirus-specific nested reverse transcription-polymerase chain reaction (RT-PCR) targeted the hantaviral L segment and metagenomic analysis., Findings: Hantavirus RNA was detected in five tissue fragments of 20 Seba's short-tailed bats (Carollia perspicillata). Phylogenetic analysis, based on partial L-segment sequence using maximum likelihood method, demonstrated that the identified virus formed a monophyletic clade and a highly divergent bat-borne lineage comprising other recent strains found in the genus Carollia from South America., Main Conclusions: Our findings suggest the presence of a novel bat-borne hantavirus in Brazil, tentatively named Mamanguape virus (MGPV). Additional genomic data will help to extend our knowledge about the classification of MGPV within the Hantaviridae family and the evolution origins of new world bat-borne hantaviruses.

The Hulunbuir region, known for its diverse terrain and rich wildlife, is a hotspot for various natural epidemic diseases. Between 2021 and 2023, we collected 885 wild rodent samples from this area, representing three families, seven genera, and eleven species. Metagenomic analysis identified three complete nucleic acid sequences from the S, M, and L segments of the Hantaviridae family, which were closely related to the Khabarovsk virus. The nucleotide coding sequences for S, M, and L (1392 nt, 3465 nt, and 6491 nt, respectively) exhibited similarities of 82.34%, 81.68%, and 81.94% to known sequences, respectively, while protein-level analysis indicated higher similarities of 94.92%, 94.41%, and 95.87%, respectively. Phylogenetic analysis placed these sequences within the same clade as the Khabarovsk, Puumala, Muju, Hokkaido, Topografov, and Tatenalense viruses, all of which are known to cause febrile diseases in humans. Immunofluorescence detection of nucleic acid-positive rodent kidney samples using sera from patients with hemorrhagic fever and renal syndrome confirmed the presence of viral particles. Based on these findings, we propose that this virus represents a new member of the Hantaviridae family, tentatively named the Amugulang virus, after its primary distribution area.

We describe a case of a 33-year-old male presented with fever, myalgia, nausea, and asthenia for six days. The patient lived in a rural area. Initial hypotheses included arbovirus infection, viral hepatitis, and Lyme disease. Reverse transcriptase polymerase chain reaction (RT-PCR) tests for Dengue, Zika, and Chikungunya resulted negative. We were able to recover complete S, L, and M segments of virus in the Orthohantavirus genome., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

From 1988-2023, Pará accounted for the highest proportion of deforestation among all states in the Brazilian Amazon. Specifically, 57.20 % of the territory in the Santa Bárbara municipality was deforested as of 2023. Since 2017, the Hantaviridae family has included viruses identified in nonrodent vertebrates, such as mobatviruses (from moles and bats). In the current metagenomic analysis of a pool of multiple organs of a Carollia brevicauda bat, we obtained sequences for three segments of the previously described Buritiense virus (BURV); to date, only the L segment had been sequenced for this mobatvirus. This study provides the first description of BURV in the Amazon region and provides information on the S and M segments of the virus. These findings corroborate the presence of BURV in Brazil in an area far from the site of the first detection and in another bat species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

To explore hantavirus infection patterns in Latin America, we conducted molecular and serologic hantavirus investigations among 3,400 febrile patients from Peru during 2020-2021. Reverse transcription PCR indicated that a patient from Loreto, in the Peruvian Amazon, was positive for Rio Mamore hantavirus (serum, 3.8 × 10 3 copies/mL). High genomic sequence identity of 87.0%-94.8% and phylogenetic common ancestry with a rodent-associated Rio Mamore hantavirus from Loreto in 1996 indicated endemicity. In 832 samples from Loreto, hantavirus incidence based on IgM ELISA of pooled Sin Nombre (SNV) and Andes virus (ANDV) nucleoproteins and immunofluorescence assay-based end-point titration using SNV/ANDV/Hantaan/Puumala/Saarema/Dobrava/Seoul hantaviruses was 0.5%. Across 3 ecologically distinct departments in Peru, SNV/ANDV IgG ELISA/IFA-based reactivity was 1.7%, suggesting circulation of antigenically distinct New World hantaviruses. Testing for arboviruses, nonendemic pathogens, and antigen-free ELISA corroborated nonspecific reactivity in 2 IgG and several IgM ELISA-positive serum samples. Hantavirus diagnostics and surveillance should be strengthened in Peru ad across Latin America.

Background: Rodent-borne orthohantaviruses are the causative agents of hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Apart from the classic rodent-borne hantaviruses, numerous species of hantaviruses have been identified in shrews and bats; however, their antigenicity and pathogenicity are unknown. This study focused on developing a serological method to detect antibodies against bat- and shrew-borne hantaviruses., Methodology/principal Findings: Five bat-borne (Brno, Dakrong, Quezon, Robina, and Xuan Song) and 6 shrew-borne (Asama, Altai, Cao Bang, Nova, Seewis, and Thottapalayam) viruses were selected based on the phylogenetic differences in their N proteins. The recombinant N (rN) proteins of these viruses were expressed as antigens in Vero E6 and 293T cell lines using the pCAGGS/MCS vector. Antisera against the Nus-tagged rN fusion proteins of these viruses (mouse anti-Brno, Dakrong, Quezon, Robina, Xuan Song, Asama, Cao Bang, and Nova, while rabbit anti-Altai, Seewis and Thottapalayam) were also generated. Antigenic cross-reactivity was examined in antisera and rN-expressing Vero E6 cells. The rN proteins of almost all the tested viruses, except for the Quezon and Robina viruses, showed independent antigenicity. For serological screening of bat samples, 5 rNs of the bat-borne viruses were expressed together in a single transfection protocol. Similarly, 6 rNs of shrew-borne viruses were expressed. Reactivities of the mixed antigen system were also examined across the singly transfected Vero cell lines to ensure that all antigens were expressed. Using these antigens, bat serum samples collected from Zambia were screened using the indirect immunofluorescence antibody test (IFAT). Selected positive samples were individually tested for the respective antigens by IFAT and western blot assays using rN-expressing 293T cell lysates. Of the 1,764 bat serum samples tested, 11.4% and 17.4% were positive for bat and shrew mixed antigens, respectively. These samples showed positive reactions to the Brno, Dakrong, Quezon, Xuan Son, Robina, Asama, Altai, Cao Bang, or Thottapalayam virus antigens., Conclusions/significance: These observations suggest that the mixed-antigen screening system is useful for serological screening For Orthohantavirus infections and that bats in Zambia are likely exposed to not only bat-borne hantaviruses but also to shrew-borne hantaviruses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sarii et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Orthohantavirus hantanense causes hemorrhagic fever with renal syndrome in Eurasia, posing a substantial public health threat. Although the Hantaan virus is the primary etiological agent in the Republic of Korea (ROK), evidence suggests the potential zoonotic transmission of the Amur virus (AMRV), closely related to the Soochong virus (SOOV), to humans in China and Russia. This study examined 31 Apodemus spp. captured from six regions in Gangwon Province, ROK, between 2015 and 2018. Of these, 5/31 (16.1%) tested positive for anti-SOOV immunoglobulin G and SOOV RNA, with 3/6 (50%) in Hongcheon-gun and 2/5 (40%) in Pyeongchang-gun. Utilizing a multiplex polymerase chain reaction-based next-generation sequencing approach, we achieved complete genomic sequencing of SOOV from rodent lung tissues, with coverage rates of 90.3%-98.2% for the S segment, 92.3%-98.1% for the M segment, and 88.1%-93.0% for the L segment. Five novel whole-genome sequences of SOOV were obtained from rodents in Hongcheon-gun and Pyeongchang-gun, representing the first documented SOOV in Pyeongchang-gun. The evolutionary rate analysis of SOOV tripartite genomes demonstrated lower divergence in the S segment. Phylogenetic analysis revealed a well-supported divergence of the SOOV and AMRV lineages across the ROK, China, and Russia, with incongruences suggesting differential segment evolution. Co-divergence analysis indicated the inter-species transmission of SOOV Aa18-104 from Apodemus agrarius in Pyeongchang-gun. The high zoonotic potential of all SOOV strains underscores the need for extensive monitoring and surveillance. This report provides crucial insights for the development of effective control strategies against hantaviral outbreaks in the ROK., (© 2024 Wiley Periodicals LLC.)

Hantavirus Pulmonary Syndrome (HPS), characterized by its high fatality rate, poses a significant public health concern in Argentina due to the increasing evidence of person-to-person transmission of Andes virus. Several orthohantaviruses were described in the country, but their phylogenetic relationships were inferred from partial genomic sequences. The objectives of this work were to assess the viral diversity of the most prevalent orthohantaviruses associated with HPS cases in the Central-East (CE) region of Argentina, elucidate the geographic patterns of distribution of each variant and reconstruct comprehensive phylogenetic relationships utilizing complete genomic sequencing. To accomplish this, a detailed analysis was conducted of the geographic distribution of reported cases within the most impacted province of the region. A representative sample of cases was then selected to generate a geographic map illustrating the distribution of viral variants. Complete viral genomes were obtained from HPS cases reported in the region, including some from epidemiologically linked cases. The phylogenetic analysis based on complete genomes defined two separate clades in Argentina: Andes virus in the Southwestern region and Andes-like viruses in other parts of the country. In the CE region, Buenos Aires virus and Lechiguanas virus clearly segregate in two subclades. Complete genomes were useful to distinguish person-to-person transmission from environmental co-exposure to rodent population. This study enhances the understanding of the genetic diversity, geographical spread, and transmission dynamics of orthohantaviruses in Central Argentina and prompt to consider the inclusion of Buenos Aires virus and Lechiguanas virus in the species Orthohantavirus andesense, as named viruses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alonso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Hemorrhagic fever with renal syndrome (HFRS) is a severe public health problem in Jiangxi province, China. Previous studies reported genetic variants of Orthohantavirus hantanense (Hantaan virus, HTNV) in rodents in this area. However, the relationship between HTNV variants and human infection needs to be confirmed. This study aimed to identify the HTNV variants in patients and to understand the clinical characteristics of HFRS caused by these variants., Methods: Samples were collected from hospitalized suspected cases of HFRS during the acute phase. HFRS cases were confirmed using quantitative real-time RT-PCR. Peripheral blood mononuclear cells (PBMC) from patients with HFRS were inoculated into Vero-E6 cells for viral isolation. The genomic sequences of HTNV from patients were obtained by amplicon-based next-generation sequencing. A retrospective analysis was conducted on the clinical characteristics of the patients., Results: HTNV RNA was detected in 53 of 183 suspected HFRS patients. Thirteen HTNVs were isolated from 32 PBMCs of HFRS cases. Whole genome sequences of 14 HTNVs were obtained, including 13 isolates in cell culture from 13 patients, and one from plasma of the fatal case which was not isolated successfully in cell culture. Genetic analysis revealed that the HTNV sequence from the 14 patients showed significant variations in nucleotide and amino acid to the HTNV strains found in other areas. Fever (100%, 53/53), thrombocytopenia (100%, 53/53), increased serum aspartate aminotransferase (100%, 53/53), and increased lactate dehydrogenase (96.2%, 51/53) were the most common characteristics. Severe acute kidney injury was observed in 13.2% (7/53) of cases. Clinical symptoms, such as pain, petechiae, and gastrointestinal or respiratory symptoms were uncommon., Conclusion: The HTNV genetic variants cause human infections in Jiangxi. The clinical symptoms of HFRS caused by the HTNV genetic variant during the acute phase are atypical. In addition to renal dysfunction, attention should be paid to the common liver injuries caused by these genetic variants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Viruses in the genus Orthohantavirus within the family Hantaviridae cause human hantavirus infections and represent a threat to public health. Hokkaido virus (HOKV), a genotype of Orthohantavirus puumalaense (Puumala virus; PUUV), was first identified in Tobetsu, Hokkaido, Japan. Although it is genetically related to the prototype of PUUV, the evolutionary pathway of HOKV is unclear. We conducted a field survey in a forest in Tobetsu in 2022 and captured 44 rodents. Complete coding genome sequences of HOKVs were obtained from five viral-RNA-positive rodents (four Myodes rufocanus bedfordiae and one Apodemus speciosus). Phylogenetic analysis revealed a close relationship between the phylogenies and geographical origins of M. rufocanus-related orthohantaviruses. Comparison of the phylogenetic trees of the S segments of orthohantaviruses and the cytochrome b genes of Myodes species suggested that Myodes-related orthohantaviruses evolved in Myodes rodent species as a result of genetic isolation and host switching., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hemorrhagic fever with renal syndrome caused by hantaviruses has long been a serious public health issue in Yunnan Province. Hantaviruses exhibit a high extent of biodiversity in their natural hosts, particularly in mammalian hosts. This study was conducted to screen for hantaviruses in bats and rodents in Yunnan Province and elucidate their genetic characteristics and possible zoonotic disease risk. Hantaviruses were detected in 202 bats and 372 rodents with the positive rates 27.49% and 1.25% respectively. A novel lineage (named Lineage 10) of the Seoul virus (SEOV) from rodents and the geographic clustering of hantavirus in bats were identified using phylogenetic analyses of the full-length M- and S-segments. Our study suggest a high cross-species transmissibility of hantaviruses in bats and existence of a new lineage of SEOV in rodents differing significantly from other SEOVs. These results provide data to support the prevention and control of hantavirus-associated diseases in Yunnan Province., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Orthohantaviruses are zoonotic pathogens that cause acute and severe syndromes in humans. This review was performed to estimate the occurrence of human orthohantaviruses in South America between 2010 and 2022. A careful evaluation of the eligibility and quality of the articles was carried out after a systematic bibliographic search of four databases. The pooled frequency of human orthohantaviruses was calculated using a random effects model meta-analysis. The heterogeneity of estimates (resulting from the chi2 test and I2 statistics) was investigated by subgroup analysis and meta-regression. 1,962 confirmed cases of orthohantavirus infections were diagnosed among 35,548 individuals from seven South American countries. The general occurrence of orthohantaviruses was estimated to be 4.4% (95% confidence interval: 2.9-6.2%) based on general pooling of human cases from 32 studies. In a subgroup analysis considering the study design and method of diagnosis, the percentages of diagnosed orthohantavirus infections differed substantially (I2 = 97.8%, p = 0.00) among South American countries. Four genetic variants of orthohantavirus have been identified circulating in Argentina, Brazil, Bolivia, Chile, Colombia, and Peru. Although laboratory diagnosis of orthohantaviruses is not performed in many countries in South America, there is evidence that four different orthohantaviruses are circulating in the region. The pooled occurrence of viral infection was approximately 4.0% in more than half of the South American countries. Updated information on the occurrence of human infections is essential for monitoring the territorial spread and determining the frequency of this zoonosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Laboratory diagnosis of orthohantavirus infection is primarily based on serology. However, for a confirmed serological diagnosis, evaluation of a follow-up serum sample is essential, which is time consuming and causes delay. Real-time reverse transcription polymerase chain reaction (RT-PCR) tests, if positive, provide an immediate and definitive diagnosis, and accurately identify the causative agent, where the discriminative nature of serology is suboptimal. We re-evaluated sera from orthohantavirus-suspected clinical cases in the Dutch regions of Twente and Achterhoek from July 2014 to April 2016 for the presence of Puumala orthohantavirus (PUUV), Tula orthohantavirus (TULV), and Seoul orthohantavirus (SEOV) RNA. PUUV RNA was detected in 11% of the total number ( n = 85) of sera tested, in 50% of sera positive for anti-PUUV/TULV IgM ( n = 16), and in 1.4% of sera negative or indeterminate for anti-PUUV/TULV IgM ( n = 69). No evidence was found for the presence of TULV or SEOV viral RNA. Based on these findings, we propose two algorithms to implement real-time RT-PCR testing in routine orthohantavirus diagnostics, which optimally provide clinicians with early confirmed diagnoses and could prevent possible further invasive testing and treatment., Importance: The addition of a real-time reverse transcription polymerase chain reaction test to routine orthohantavirus diagnostics may better aid clinical decision making than the use of standard serology tests alone. Awareness by clinicians and clinical microbiologists of this advantage may ultimately lead to a reduction in over-hospitalization and unnecessary invasive diagnostic procedures., Competing Interests: The authors declare no conflict of interest.

Few cases of hantavirus pulmonary syndrome have been reported in northeastern Argentina. However, neighboring areas show a higher incidence, suggesting underreporting. We evaluated the presence of antibodies against orthohantavirus in small rodents throughout Misiones province. Infected Akodon affinis montensis and Oligoryzomys nigripes native rodents were found in protected areas of Misiones.

Bats are known reservoirs of various emerging pathogens, and have recently been found to host a novel hantavirus, named Brno loanvirus (BRNV), from the Mammantavirinae subfamily (family Hantaviridae, order Bunyavirales). Here we report BRNV detection in bats from the urban area of Brno, Czech Republic in March 2022. Specifically, we uncovered a high prevalence of BRNV (8.8%, 5/57) among hibernating bats (Nyctalus noctula) in urban area, which poses a risk of human exposure. The positive bats included adult females (3/9 positive), a juvenile female (1/32 positive), and an adult male (1/6 positive). All 10 juvenile males were negative. We used RT-qPCR to quantify the BRNV RNA levels in various bat organs, which yielded positive results for viral RNA in organs, including the kidneys, heart, spleen, brain, liver, lung, and gut, and in body cavity fluid. Among all tested organs, the liver showed the highest levels of viral RNA in 4 out of 5 animals examined (average Ct value of 20.8 ± 7.4)., Competing Interests: Declaration of competing interest All authors declare no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Orthohantaviruses, transmitted primarily by rodents, cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in the Americas. These viruses, with documented human-to-human transmission, exhibit a wide case-fatality rate, 0.5-40 %, depending on the virus species, and no vaccine or effective treatment for severe Orthohantavirus infections exists. In Europe, the Puumala virus (PUUV), carried by the bank vole Myodes glareolus, causes a milder form of HFRS. Despite the reliance on serology and PCR for diagnosis, the three genomic segments of Swedish wild-type PUUV have yet to be completely sequenced. We have developed a targeted hybrid-capture method aimed at comprehensive genomic sequencing of wild-type PUUV isolates and the identification of other Orthohantaviruses. Our custom-designed panel includes >11,200 probes covering the entire Orthohantavirus genus. Using this panel, we sequenced complete viral genomes from bank vole lung tissue, human plasma samples, and cell-cultured reference strains. Analysis revealed that Swedish PUUV isolates belong to the Northern Scandinavian lineage, with nucleotide diversity ranging from 2.8 % to 3.7 % among them. Notably, no significant genotypic differences were observed between the viral sequences from reservoirs and human cases except in the nonstructural protein. Despite the high endemicity of PUUV in Northern Sweden, these are the first complete Swedish wild-type PUUV genomes and substantially increase our understanding of PUUV evolution and epidemiology. The panel's sensitivity enables genomic sequencing of human samples with viral RNA levels reflecting the natural progression of infection and underscores our panel's diagnostic value, and could help to uncover novel Orthohantavirus transmission routes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: High incidences of haemorrhagic fever with renal syndrome (HFRS) have been reported in the southern Republic of Korea (ROK). A distinct southern genotype of Orthohantavirus hantanense (HTNV) was identified in Apodemus agrarius chejuensis on Jeju Island. However, its association with HFRS cases in southern ROK remains elusive. We investigated the potential of the southern HTNV genotype as an etiological agent of HFRS., Methods: Samples from 22 patients with HFRS and 193 small mammals were collected in the southern ROK. The clinical characteristics of patients infected with the southern HTNV genotype were analysed. Amplicon-based MinION sequencing was employed for southern HTNV from patients and rodents, facilitating subsequent analyses involving phylogenetics and genetic reassortment., Results: High-throughput sequencing of HTNV exhibited higher coverage with a cycle of threshold value below 32, acquiring nearly whole-genome sequences from six patients with HFRS and seven A. agrarius samples. The phylogenetic pattern of patient-derived HTNV demonstrated genetic clustering with HTNV from Apodemus species on Jeju Island and the southern Korean peninsula, revealing genetic reassortment in a single clinical sample between the M and S segments., Discussion: These findings imply that the southern HTNV genotype has the potential to induce HFRS in humans. The phylogenetic inference demonstrates the diverse and dynamic characteristics of the southern HTNV tripartite genomes. Therefore, this study highlights the significance of active surveillance and amplicon sequencing for detecting orthohantavirus infections. It also raises awareness and caution for physicians regarding the emergence of a southern HTNV genotype as a cause of HFRS in the ROK., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

To date, six hantavirus species have been detected in moles (family Talpidae). In this report, we describe Academ virus (ACDV), a novel hantavirus harbored by the Siberian mole ( Talpa altaica ) in Western Siberia. Genetic analysis of the complete S-, M-, and partial L-genomic segments showed that ACDV shared a common evolutionary origin with Bruges virus, previously identified in the European mole ( Talpa europaea ), and is distantly related to other mole-borne hantaviruses. Co-evolution and local adaptation of genetic variants of hantaviruses and their hosts, with possible reassortment events, might have shaped the evolutionary history of ACDV.

Hemorrhagic fever with renal syndrome (HFRS) is a zoonosis characterized by clinical features of high fever, hemorrhage, and renal damage. China has the largest number of HFRS cases worldwide, accounting for over 90% of the total reported cases. In this paper, we used surveyed HFRS data and satellite imagery to conduct geostatistical analysis for investigating the associations of rapid urbanization, water bodies, and other factors on the spatiotemporal dynamics of HFRS from year 2005 to 2018 in Xi'an City, Northwest China. The results revealed an evident epidemic aggregation in the incidence of HFRS within Xi'an City with a phenomenal fluctuation in periodic time series. Rapid urbanization was found to greatly affect the HFRS incidence in two different time phases. HFRS caused by urbanization influences farmers to a lesser extent than it does to non-farmers. The association of water bodies with the HFRS incidence rate was found to be higher within the radii of 696.15 m and 1575.39 m, which represented significant thresholds. The results also showed that geomatics approaches can be used for spatiotemporally investigating the HFRS dynamic characteristics and supporting effective allocations of resources to formulate strategies for preventing epidemics., Competing Interests: The authors have declared that no competing interests exist.

Orthohantaviruses are emerging rodent-borne pathogens that cause Hantavirus Pulmonary Syndrome in humans. They have a wide range of rodent reservoir hosts and are transmitted to humans through aerosolized viral particles generated by the excretions of infected individuals. Since the first description of HPS in Argentina, new hantaviruses have been reported throughout the country, most of which are pathogenic to humans. We present here the first HPS case infected with Alto Paraguay virus reported in Argentina. Until now, Alto Paraguay virus was considered a non-pathogenic orthohantavirus since it was identified in a rodent, Holochilus chacarius. In addition to this, with the goal of identifying potential hantavirus host species in the province of Santa Fe, we finally describe a novel orthohantavirus found in the native rodent Scapteromys aquaticus, which differed from other hantaviruses described in the country so far. Our findings implicate an epidemiological warning regarding these new orthohantaviruses circulating in Central Argentina as well as new rodent species that must be considered as hosts from now on., Competing Interests: The authors have declared that no competing interests exist.

In Europe, two species of hantaviruses, Puumala orthohantavirus (PUUV) and Dobrava orthohantavirus (DOBV), cause hemorrhagic fever with renal syndrome in humans. The rodent reservoirs for these viruses are common throughout Ukraine, and hence, the goal of this study was to identify the species and strains of hantaviruses circulating in this region. We conducted surveillance of small rodent populations in a rural region in northwestern Ukraine approximately 30 km from Poland. From the 424 small mammals captured, we identified nine species, of which the most abundant were Myodes glareolus , the bank vole (45%); Apodemus flavicollis , the yellow-necked mouse (29%); and Apodemus agrarius , the striped field mouse (14.6%) Using an indirect immunofluorescence assay, 15.7%, 20.5%, and 33.9% of the sera from M. glareolus , A. glareolus , and A. flavicollis were positive for hantaviral antibodies, respectively. Additionally, we detected antibodies to the hantaviral antigen in one Microtus arvalis , one Mus musculus , and one Sorex minutus . We screened the lung tissue for hantaviral RNA using next-generation sequencing and identified PUUV sequences in 25 small mammals, including 23 M. glareolus , 1 M. musculus , and 1 A. flavicollis, but we were unable to detect DOBV sequences in any of our A. agrarius specimens. The percent identity matrix and Bayesian phylogenetic analyses of the S-segment of PUUV from 14 M. glareolus lungs suggest the highest similarity (92-95% nucleotide or 99-100% amino acid) with the Latvian lineage. This new genetic information will contribute to future molecular surveillance of human cases in Ukraine.

The discovery of genetically distinct hantaviruses (family Hantaviridae ) in multiple species of shrews, moles and bats has revealed a complex evolutionary history involving cross-species transmission. Seewis virus (SWSV) is widely distributed throughout the geographic ranges of its soricid hosts, including the Eurasian common shrew ( Sorex araneus ), tundra shrew ( Sorex tundrensis ) and Siberian large-toothed shrew ( Sorex daphaenodon ), suggesting host sharing. In addition, genetic variants of SWSV, previously named Artybash virus (ARTV) and Amga virus, have been detected in the Laxmann's shrew ( Sorex caecutiens ). Here, we describe the geographic distribution and phylogeny of SWSV and Altai virus (ALTV) in Asian Russia. The complete genomic sequence analysis showed that ALTV, also harbored by the Eurasian common shrew, is a new hantavirus species, distantly related to SWSV. Moreover, Lena River virus (LENV) appears to be a distinct hantavirus species, harbored by Laxmann's shrews and flat-skulled shrews ( Sorex roboratus ) in Eastern Siberia and far-eastern Russia. Another ALTV-related virus, which is more closely related to Camp Ripley virus from the United States, has been identified in the Eurasian least shrew ( Sorex minutissimus ) from far-eastern Russia. Two highly divergent viruses, ALTV and SWSV co-circulate among common shrews in Western Siberia, while LENV and the ARTV variant of SWSV co-circulate among Laxmann's shrews in Eastern Siberia and far-eastern Russia. ALTV and ALTV-related viruses appear to belong to the Mobatvirus genus, while SWSV is a member of the Orthohantavirus genus. These findings suggest that ALTV and ALTV-related hantaviruses might have emerged from ancient cross-species transmission with subsequent diversification within Sorex shrews in Eurasia.

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., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

European orthohantaviruses (Puumala orthohantavirus (PUUV); Dobrava-Belgrade orthohantavirus (DOBV), genotype Kurkino; Tula orthohantavirus (TULV)), and Leptospira spp. are small mammal-associated zoonotic pathogens that cause diseases with potentially similar symptoms in humans. We investigated the frequency of Leptospira spp. and hantavirus single and double infections in small mammals from 22 sites in Thuringia, central Germany, during 2017. TULV infections were detected at 18 of 22 sites (mean prevalence 13.8%, 93/674). PUUV infections were detected at four of 22 sites (mean prevalence 1.5%, 7/471), and respective PUUV sequences formed a novel phylogenetic clade, but DOBV infections were not detected at all. Leptospira infections were detected at 21 of 22 sites with the highest overall prevalence in field voles (Microtus agrestis) with 54.5% (6/11) and common voles (Microtus arvalis) with 30.3% (205/676). Leptospira-hantavirus coinfections were found in 6.6% (44/671) of common voles but only in two of 395 bank voles. TULV and Leptospira coinfection probability in common voles was driven by individual (age) and population-level factors. Coinfections seemed to be particularly associated with sites where Leptospira spp. prevalence exceeded 35%. Future investigations should evaluate public health consequences of this strong spatial clustering of coinfections.

Background: Rodent borne hantaviruses are emerging viruses infecting humans through inhalation. They cause hemorrhagic fever with renal syndrome and hemorrhagic cardiopulmonary syndrome. Recently, hantaviruses have been detected in other small mammals such as Soricomorpha (shrews, moles) and Chiroptera (bats), suggested as reservoirs for potential pandemic viruses and to play a role in the evolution of hantaviruses. It is important to study the global virome in different reservoirs, therefore our aim was to investigate whether shrews in Sweden carried any hantaviruses. Moreover, to accurately determine the host species, we developed a molecular method for identification of shrews., Method: Shrews (n = 198), caught during 1998 in Sweden, were screened with a pan-hantavirus PCR using primers from a conserved region of the large genome segment. In addition to morphological typing of shrews, we developed a molecular based typing method using sequencing of the mitochondrial cytochrome C oxidase I (COI) and cytochrome B (CytB) genes. PCR amplified hantavirus and shrew fragments were sequenced and phylogenetically analysed., Results: Hantavirus RNA was detected in three shrews. Sequencing identified the virus as Seewis hantavirus (SWSV), most closely related to previous isolates from Finland and Russia. All three SWSV sequences were retrieved from common shrews (Sorex araneus) sampled in Västerbotten County, Sweden. The genetic assay for shrew identification was able to identify native Swedish shrew species, and the genetic typing of the Swedish common shrews revealed that they were most similar to common shrews from Russia., Conclusion: We detected SWSV RNA in Swedish common shrew samples and developed a genetic assay for shrew identification based on the COI and CytB genes. This was the first report of presence of hantavirus in Swedish shrews.

Rodent-borne hantaviruses have been reported in many of the countries surrounding Ukraine; however, to date we have no knowledge of the viral strains circulating in Ukraine within reservoirs such as the striped field mouse ( Apodemus agrarius ), the yellow-necked field mouse ( Apodemus flavicollis ), and the bank vole ( Myodes glareolus ). To determine the prevalence of hantaviruses in Ukraine, we captured 1,261 mammals, of which 1,109 were rodents, in 58 field sites within the province of Volyn in western Ukraine. Foci of the striped field mouse tended to occur in the eastern and southern parts of the province, whereas the bank vole were clustered in western and northern regions. The striped field mouse and bank vole had detectable serum antibodies to Puumala virus (PUUV) or Dobrava virus (DOBV) antigens at 7% or 2%, respectively, using an indirect immunofluorescence assay. Antibody prevalence among the bank vole males and females was equivalent, whereas for the striped field mouse, the prevalence among males was 5% versus 1% for females. In two bank vole specimens, we were able to detect partial nucleotide sequences that showed identity to PUUV. In summary, this study suggests that two human pathogens, PUUV and DOBV, cocirculate in the bank vole and the striped field mouse, respectively, in Ukraine. Future studies will focus on new rodent collections that will enable obtaining the complete genome sequences of the PUUV and DOBV strains circulating in Ukraine to provide guidance on the design of optimal molecular diagnostics that can enable insight into the potential contribution of hantaviruses to human disease in Ukraine.

Objective: Orthohantaviruses are geographically widely distributed and present various clinical manifestations from mild symptoms to the severe form of haemorrhagic fever with renal syndrome (HFRS) in Eurasia. Official registration of HFRS in Kazakhstan started in the year 2000. However, the true prevalence of human infections by orthohantaviruses within Kazakhstan is unknown. The aim of this study was to investigate of the seroprevalence of orthohantavirus infections in patients with fever of unknown origin (FUO) in two regions, Almaty and Kyzylorda region., Methods: Paired serum samples from 802 patients with FUO were screened for the presence of orthohantavirus IgG and IgM antibodies by ELISA. Positive samples were further tested by immunoblotting and indirect immunofluorescence tests (IIFT) to determine the respective orthohantavirus serotypes. Suspected acute serum samples were additionally checked by a RT-PCR to identify viral RNA., Results: In total 178/802 (22.2%) serum samples reacted with orthohantavirus IgG antibodies and 4/802 (0.5%) with IgM antibodies. All positive samples were tested by immunoblotting which resulted in 2.9% positive samples with IgG antibodies against Puumala (PUUV), Hantaan (HTNV) and Dobrava (DOBV) virus serotypes in Almaty region and 5.4% to PUUV and DOBV serotypes in Kyzylorda region, respectively. In the IFFT, 1.9% positive samples from Almaty and 3.1% from Kyzylorda were confirmed for PUUV and DOBV serotypes. Out of four IgM ELISA positive samples only three were positive against PUUV in the immunoblot and showed weak positive reactivity for the Saaremaa (SAAV), PUUV and HTNV serotypes in the IFFT., Conclusions: This study demonstrates the presence of orthohantavirus infections among patients with FUO in Kazakh regions that were so far considered as non-endemic. The healthcare system needs to be prepared accordingly in order to be capable of detecting cases and providing adequate management of patients., (© 2020 The Authors. Zoonoses and Public Health published by Blackwell Verlag GmbH.)

Orthohantaviruses are globally distributed viruses, associated with rodents and other small mammals. However, data on the circulation of orthohantaviruses within the UK, particularly the UK-endemic Tatenale virus, is sparse. In this study, 531 animals from five rodent species were collected from two locations in northern and central England and screened using a degenerate, pan- orthohantavirus RT-PCR assay. Tatenale virus was detected in a single field vole ( Microtus agrestis ) from central England and twelve field voles from northern England. Unbiased high-throughput sequencing of the central English strain resulted in the recovery of the complete coding sequence of a novel strain of Tatenale virus, whilst PCR-primer walking of the northern English strain recovered almost complete coding sequence of a previously identified strain. These findings represented the detection of a third lineage of Tatenale virus in the United Kingdom and extended the known geographic distribution of these viruses from northern to central England. Furthermore, the recovery of the complete coding sequence revealed that Tatenale virus was sufficiently related to the recently identified Traemersee virus, to meet the accepted criteria for classification as a single species of orthohantavirus.

Orthohantaviruses are negative-sense, single-stranded RNA viruses harbored by rodents, shrews, moles, and bats. Of the shrew-borne orthohantaviruses in the Republic of Korea (ROK), Jeju orthohantavirus (Jeju virus, JJUV) was found on Jeju Island. This small-scale epidemiologic survey investigated the geographic distribution and molecular phylogeny of JJUV in the ROK. In 32 trapping sites, tissues of 84 Crocidura shantungensis were analyzed for JJUV RNA. JJUV RNA was detected in seven (8.3%) shrews captured on the Korean peninsula. The molecular epidemiologic survey demonstrated the prevalence of JJUV by geographic distribution. The RNA loads of JJUV were evaluated in various tissues. Entire coding sequences of tripartite genomes were recovered from two JJUV strains on the mainland. Phylogenetic relationships of the JJUV revealed a distinct geographic lineage of mainland strains from the strains on Jeju Island. This study sheds light on the molecular epidemiology, phylogeographic diversity, and virus-host co-divergence of JJUV, ROK., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To date, only two rodent-borne hantaviruses have been detected in sub-Saharan Africa. Here, we report the detection of a yet unknown hantavirus in a Natal mastomys (Mastomys natalensis) in Méliandou, Guinea, in 2014. The phylogenetic placement of this virus suggests that it might represent a cross-order spillover event from an unknown bat or eulipotyphlan host.

Hantavirus Pulmonary Syndrome is an, often fatal, emerging zoonotic disease in the Americas caused by hantaviruses (family: Hantaviridae). In Brazil, hantavirus routine diagnosis is based on serology (IgM-ELISA) while RT-PCR is often used to confirm acute infection. A Semi-nested RT-PCR and an internally controlled RT-qPCR assays were developed for detection and quantification of four hantaviruses strains circulating in the Brazilian Amazon: Anajatuba (ANAJV) and Castelo dos Sonhos (CASV) strains of Andes virus (ANDV) species; and Rio Mamoré (RIOMV) and Laguna Negra (LNV) strains of LNV species. A consensus region in the N gene of these hantaviruses was used to design the primer sets and a hydrolysis probe. In vitro transcribed RNA was diluted in standards with known concentration. MS2 bacteriophage RNA was detected together with hantavirus RNA as an exogenous control in a duplex reaction. RT-qPCR efficiency was around 100% and the limit of detection was 0.9 copies/μL of RNA for RT-qPCR and 10 copies/μL of RNA for Semi-nested RT-PCR. There was no amplification of either negative samples or samples positive to other pathogens. To assess the protocol for clinical sensitivity, specificity and general accuracy values, both assays were used to test two groups of samples: one comprising patients with disease (n = 50) and other containing samples from healthy individuals (n = 50), according to IgM-ELISA results. A third group of samples (n = 27) infected with other pathogens were tested for specificity analysis. RT-qPCR was more sensitive than semi-nested RT-PCR, being able to detect three samples undetected by conventional RT-PCR. RT-qPCR clinical sensitivity, specificity and general accuracy values were 92.5%, 100% and 97.63%, respectively. Thus, the assays developed in this study were able to detect the four Brazilian Amazon hantaviruses with good specificity and sensitivity, and may become powerful tools in diagnostic, surveillance and research applications of these and possibly other hantaviruses., Competing Interests: The authors have declared that no competing interests exist.

The pathogenicity of the shrew-borne Imjin virus (MJNV) is unknown. The objective of our study was to find serological evidence of MJNV infection in humans. Partial MJNV nucleocapsid protein (NP) was cloned and expressed as an antigen for double-antigen sandwich ELISA, IgM capture ELISA, and dot blot to detect MJNV specific antibodies in hemorrhagic fever with renal syndrome (HFRS) patients' and healthy persons' sera from endemic areas in China. The purified recombinant NP reacted with neither the 90 healthy individuals' sera from non-endemic areas of MJNV nor the 100 antisera to HFRS-causing virus, indicating that the MJNV NP had no cross-reaction with normal human sera and HFRS-causing viral antibodies. As determined by screening ELISA and dot blot analysis, IgG antibodies against MJNV NP were detected in sera from two of 385 healthy individuals from MJNV-endemic areas, suggesting infection with MJNV or MJNV-like thottimvirus. Based on the suggestive evidence, healthcare workers should be alert to febrile diseases occurring among individuals with exposure to shrew-infested habitats.

We have reported high seroprevalence to Thailand orthohantavirus (THAIV) or THAIV-related orthohantavirus (TRHV) among patients with chronic kidney disease of unknown etiology in Girandurukotte, Sri Lanka. THAIV or TRHV infection is considered to be transmitted by rodent hosts in this area, but its reservoir rodents have not yet been identified. Hence, 116 rodents were captured, and seroprevalences were examined by indirect immunofluorescent antibody assay (immunofluorescence assay [IFA]) using antigens of THAIV strain Thai749-infected Vero E6 cells and recombinant nucleocapsid protein of THAIV expressed in Vero E6 cell. Molecular biological species identification of rodents was carried out by sequencing rag1 , irbp , and mitochondrial cytb genes. The majority (112/116) of the captured rodents were lineage Ib of black rats ( Rattus rattus ). Among them, 19.6% (22/112) of the rats possessed antibodies against THAIV. Also, a lesser bandicoot rat ( Bandicota bengalensis ), which belongs to the Sri Lankan endemic genetic lineage, was seropositive (1/1). Two Mus booduga and one Murinae sp. were seronegative. Rodent sera showed less cross-reactivities to antigens of Vero E6 cells infected with Hantaan orthohantavirus (HTNV), Seoul orthohantavirus (SEOV), and Puumala orthohantavirus (PUUV) in IFA. These results suggest that the hantavirus present in rodents in Sri Lanka is related to THAIV or TRHV rather than to SEOV, HTNV, or PUUV. However, it might be serologically distinct from the prototype THAIV strain, Thai749, used in this study. This study revealed that black rats and lesser bandicoot rats belonging to Sri Lankan endemic lineages are possible reservoirs for THAIV or TRHV in Girandurukotte. Further multiple geographical studies are needed to confirm the THAIV or TRHV reservoir status of black and lesser bandicoot rats in Sri Lanka.

Although most of Arvicolinae associated hantaviruses can not cause disease in humans, hemorrhagic fever with renal syndrome (HFRS) cases caused by Tula virus (TULV) have been described in Europe since 2002. In addition to Europe, TULV was also identified in the Microtus arvalis obscurus voles sampled from Kazakhstan, which shares borders with China. To gain more insight into the molecular epidemiology of TULV, a total of 365 rodents representing 7 species of 4 subfamily (Arvicolinae, Murinae, Gerbillinae, and Cricetinae) were captured in Qapqal county, Xinjiang, northwest China. Hantavirus RNA was recovered from 40 lung tissue samples of M. arvalis obscurus, with the prevalence of 10.96%. Genetic analysis revealed that all recovered viral sequences were most closely related to those of TULV, but exhibited >11% nucleotide differences from all currently known TULV, suggesting that they may represent a new subtype of TULV. In the S tree, the newly identified viruses formed a distinct lineage and showed a close evolutionary relationship with those sampled from Southwestern Siberia and Kazakhstan. However, they exhibited a different clustering pattern in both the M and the L trees, suggesting the possibility of genetic reassortment. Finally, the recombination event was also observed in Xinjiang TULV viruses. In sum, all these data reveal a complex evolutionary history of TULV in Central Asia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Insectivores are the new emerging reservoir of hantaviruses. Here, we describe Lena virus (LENV), a novel hantavirus harbored by the Laxmann`s shrew (Sorex caecutiens), which is also the host of Artybash virus (ARTV). Genetic analysis of the complete genomic sequence shows that LENV is in distant relation to ARTV and other Sorex-borne hantaviruses, suggesting that LENV has emerged from cross-species transmission. Additionally, new genetic variant of ARTV, designated as ARTV-St, was identified in tundra shrews (Sorex tundrensis). Finally, distinct insectivore-borne hantaviruses are co-circulating in the same localities of far eastern Russia: LENV, ARTV and Yakeshi in the forest site, while ARTV, ARTV-St, and Kenkeme virus in the meadow field site., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the past ten years, several novel hantaviruses were discovered in shrews, moles, and bats, suggesting the dispersal of hantaviruses in many animal taxa other than rodents during their evolution. Interestingly, the coevolutionary analyses of most recent studies have raised the possibility that nonrodents may have served as the primordial mammalian host and harboured the ancestors of rodent-borne hantaviruses as well. The aim of our study was to investigate the presence of hantaviruses in bat lung tissue homogenates originally collected for taxonomic purposes in Malaysia in 2015. Hantavirus-specific nested RT-PCR screening of 116 samples targeting the L segment of the virus has revealed the positivity of two lung tissue homogenates originating from two individuals, a female and a male of the Murina aenea bat species collected at the same site and sampling occasion. Nanopore sequencing of hantavirus positive samples resulted in partial genomic data from S, M, and L genome segments. The obtained results indicate molecular evidence for hantaviruses in the M. aenea bat species. Sequence analysis of the PCR amplicon and partial genome segments suggests that the identified virus may represent a novel species in the Mobatvirus genus within the Hantaviridae family. Our results provide additional genomic data to help extend our knowledge about the evolution of these viruses.

With the recent discovery of genetically distinct hantaviruses (family Hantaviridae ) in shrews (order Eulipotyphla, family Soricidae), the once-conventional view that rodents (order Rodentia) served as the primordial reservoir hosts now appears improbable. The newly identified soricid-borne hantaviruses generally demonstrate well-resolved lineages organized according to host taxa and geographic origin. However, beginning in 2007, we detected sequences that did not conform to the prototypic hantaviruses associated with their soricid host species and/or geographic locations. That is, Eurasian common shrews ( Sorex araneus ), captured in Hungary and Russia, were found to harbor hantaviruses belonging to two separate and highly divergent lineages. We have since accumulated additional examples of these highly distinctive hantavirus sequences in the Laxmann's shrew ( Sorex caecutiens ), flat-skulled shrew ( Sorex roboratus ) and Eurasian least shrew ( Sorex min u tissimus ), captured at the same time and in the same location in the Sakha Republic in Far Eastern Russia. Pair-wise alignment and phylogenetic analysis of partial and full-length S-, M- and/or L-segment sequences indicate that a distinct hantavirus species related to Altai virus (ALTV), first reported in a Eurasian common shrew from Western Siberia, was being maintained in these closely related syntopic soricine shrew species. These findings suggest that genetic variants of ALTV might have resulted from ancient host-switching events with subsequent diversification within the Soricini tribe in Eurasia., Competing Interests: The authors declare no conflicts of interest.

Background: Hemorrhagic fever with renal syndrome (HFRS) is an emerging zoonotic infectious disease caused by hantaviruses which circulate worldwide. So far, it was still considered as one of serious public health problems in China. The present study aimed to reveal the stabilities and variations of hantavirus infection in Hebei province located in North China through a long-term retrospective observation., Methods: The epidemiological data of HFRS cases from all 11 cities of Hebei province since 1981 through 2016 were collected and descriptively analyzed. The rodent densities, species compositions and virus-carrying rates of different regions were collected from six separated rodent surveillance points which set up since 2007. The molecular diversity and phylogenetic relationship of hantaviruses circulating among rodents were analyzed based on partial viral glycoprotein gene., Results: HFRS cases have been reported every year in Hebei province, since the first local case was identified in 1981. The epidemic history can be artificially divided into three phases and a total of 55,507 HFRS cases with 374 deaths were reported during 1981-2016. The gender and occupational factors of susceptible population were invarible throughout, however age of that was gradually aging. The annual outbreak peak always present in spring, while the main epidemic region had gradully altered from south to northeast. Surveillance of rodents revealed that residential rodents significantly possessed higher density and virus-carring rate than field rodents. The house rat, Rattus norvegicus, was the dominant rodent species and Seoul virus S3 sub-genotype which is continued but slightly evolving perhaps to be the sole pathogen for local HFRS cases of Hebei province., Conclusions: This long-term province-wide surveillance and epidemiological analysis has revealed the stabilities and variations of hantavirus infection in North China. In order to improve current prevention and control strategies of HFRS in China, all surveillance should be continuously enhanced and variations should be paid more attentions.

In recent years, negative-sense RNA virus classification and taxon nomenclature have undergone considerable transformation. In 2016, the new order Bunyavirales was established, elevating the previous genus Hantavirus to family rank, thereby creating Hantaviridae . Here we summarize affirmed taxonomic modifications of this family from 2016 to 2019. Changes involve the admission of >30 new hantavirid species and the establishment of subfamilies and novel genera based on DivErsity pArtitioning by hieRarchical Clustering (DEmARC) analysis of genomic sequencing data. We outline an objective framework that can be used in future classification schemes when more hantavirids sequences will be available. Finally, we summarize current taxonomic proposals and problems in hantavirid taxonomy that will have to be addressed shortly.

Hantaviruses are zoonotic agents transmitted from small mammals, mainly rodents, to humans, where they provoke diseases such as Hemorrhagic fever with Renal Syndrome (HFRS) and its mild form, Nephropathia Epidemica (NE), or Hantavirus Cardio-Pulmonary Syndrome (HCPS). Hantaviruses are spread worldwide and monitoring animal reservoirs is of primary importance to control the zoonotic risk. Here, we describe the development of a pan-viral resequencing microarray (PathogenID v3.0) able to explore the genetic diversity of rodent-borne hantaviruses endemic in Europe. Among about 800 sequences tiled on the microarray, 52 correspond to a tight molecular sieve of hantavirus probes covering a large genetic landscape. RNAs from infected animal tissues or from laboratory strains have been reverse transcribed, amplified, then hybridized to the microarray. A classical BLASTN analysis applied to the sequence delivered through the microarray allows to identify the hantavirus species up to the exact geographical variant present in the tested samples. Geographical variants of the most common European hantaviruses from France, Germany, Slovenia and Finland, such as Puumala virus, Dobrava virus and Tula virus, were genetically discriminated. Furthermore, we precisely characterized geographical variants still unknown when the chip was conceived, such as Seoul virus isolates, recently emerged in France and the United Kingdom.

Several viruses from the genus Orthohantavirus are known to cause lethal disease in humans. Sigmodontinae rodents are the main hosts responsible for hantavirus transmission in the tropical forests, savannas, and wetlands of South America. These rodents can shed different hantaviruses, such as the lethal and emerging Araraquara orthohantavirus. Factors that drive variation in host populations may influence hantavirus transmission dynamics within and between populations. Landscape structure, and particularly areas with a predominance of agricultural land and forest remnants, is expected to influence the proportion of hantavirus rodent hosts in the Atlantic Forest rodent community. Here, we tested this using 283 Atlantic Forest rodent capture records and geographically weighted models that allow us to test if predictors vary spatially. We also assessed the correspondence between proportions of hantavirus hosts in rodent communities and a human vulnerability to hantavirus infection index across the entire Atlantic Forest biome. We found that hantavirus host proportions were more positively influenced by landscape diversity than by a particular habitat or agricultural matrix type. Local small mammal diversity also positively influenced known pathogenic hantavirus host proportions, indicating that a plasticity to habitat quality may be more important for these hosts than competition with native forest dwelling species. We found a consistent positive effect of sugarcane and tree plantation on the proportion of rodent hosts, whereas defaunation intensity did not correlate with the proportion of hosts of potentially pathogenic hantavirus genotypes in the community, indicating that non-defaunated areas can also be hotspots for hantavirus disease outbreaks. The spatial match between host hotspots and human disease vulnerability was 17%, while coldspots matched 20%. Overall, we discovered strong spatial and land use change influences on hantavirus hosts at the landscape level across the Atlantic Forest. Our findings suggest disease surveillance must be reinforced in the southern and southeastern regions of the biome where the highest predicted hantavirus host proportion and levels of vulnerability spatially match. Importantly, our analyses suggest there may be more complex rodent community dynamics and interactions with human disease than currently hypothesized., Competing Interests: The authors have declared that no competing interests exist.

IntroductionTwo hantavirus species, Puumala (PUUV) and Dobrava-Belgrade (DOBV) virus (genotype Kurkino), are endemic in Germany. Recent PUUV outbreaks raised questions concerning increasing frequency of outbreaks and expansion of PUUV endemic areas.AimsTo describe the epidemiology of human PUUV and DOBV infections in Germany.MethodsWe conducted an observational retrospective study analysing national hantavirus surveillance data notified to the national public health institute and hantavirus nucleotide sequences from patients collected at the national consultation laboratory between 2001 and 2017. Matching molecular sequences with surveillance data, we conducted epidemiological, phylogenetic and phylogeographic analyses.ResultsIn total, 12,148 cases of symptomatic hantavirus infection were notified 2001-17 (mean annual incidence: 0.87/100,000; range: 0.09-3.51). PUUV infections showed a highly variable space-time disease incidence pattern, causing large outbreaks every 2-3 years with peaks in early summer and up to 3,000 annually reported cases. Sex-specific differences in disease presentation were observed. Of 202 PUUV nucleotide sequences obtained from cases, 189 (93.6%) fall into well-supported phylogenetic clusters corresponding to different endemic areas in Germany. DOBV infections caused few, mostly sporadic cases in autumn and winter in the north and east of Germany.ConclusionsThe frequency of PUUV outbreaks increased between 2001 and 2017 but our data does not support the suggested expansion of endemic areas. The epidemiology of PUUV and DOBV-Kurkino infections differs in several aspects. Moreover, the latter are relatively rare and combining efforts and data of several countries to identify risk factors and develop specific recommendations for prevention could be worthwhile.

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.

The recent discovery of genetically distinct shrew- and mole-borne viruses belonging to the newly defined family Hantaviridae (order Bunyavirales) has spurred an extended search for hantaviruses in RNAlater®-preserved lung tissues from 215 bats (order Chiroptera) representing five families (Hipposideridae, Megadermatidae, Pteropodidae, Rhinolophidae and Vespertilionidae), collected in Vietnam during 2012 to 2014. A newly identified hantavirus, designated Đakrông virus (DKGV), was detected in one of two Stoliczka's Asian trident bats (Aselliscus stoliczkanus), from Đakrông Nature Reserve in Quảng Trị Province. Using maximum-likelihood and Bayesian methods, phylogenetic trees based on the full-length S, M and L segments showed that DKGV occupied a basal position with other mobatviruses, suggesting that primordial hantaviruses may have been hosted by ancestral bats.

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.

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.