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Sample records for riesgo para hantavirus

  1. Hantavirus

    MedlinePlus

    Hantavirus pulmonary syndrome; Hemorrhagic fever with renal syndrome ... DA. California encephalitis, hantavirus pulmonary syndrome, and bunyavirus hemorrhagic fevers. In: Bennett JE, Dolin R, Blaser MJ, eds. ...

  2. Hantavirus Pulmonary Syndrome (HPS)

    MedlinePlus

    ... this page: About CDC.gov . Hantavirus Share Compartir Hantavirus Pulmonary Syndrome (HPS) Severe HPS. Image courtesy D. ... the workers showed evidence of infection or illness. Hantavirus Pulmonary Syndrome (HPS) Topics Transmission Where HPS is ...

  3. Uso de Sustancias en Mujeres con Desventaja Social: Riesgo para el Contagio de VIH/SIDA

    PubMed Central

    Cianelli, R.; Ferrer, L; Bernales, M.; Miner, S.; Irarrázabal, L.; Molina, Y.

    2009-01-01

    Antecedentes La caracterización epidemiológica en Chile apunta a feminización, pauperización y heterosexualización de la epidemia del VIH, lo que implica un mayor riesgo para las mujeres en desventaja social. Si a esto se suma la utilización de sustancias, la vulnerabilidad de este grupo frente al VIH/SIDA aumenta. Objetivo Describir el uso de sustancias en mujeres con desventaja social e identificar factores de riesgo de contagio de VIH, asociados a este consumo. Material y Método 52 mujeres fueron entrevistadas como parte del proyecto “Testeando una intervención en prevención de VIH/SIDA en mujeres chilenas” GRANT # RO1 TW 006977. Se describen variables sociodemográficas y de consumo de sustancias a través de estadísticas descriptivas y se analiza la relación entre variables a través de pruebas de correlación. Resultados Los resultados indican un perfil sociodemográfico que sitúa a las mujeres en situación de vulnerabilidad frente al contagio de VIH/SIDA, con alto índice de uso de sustancias que acentúa el riesgo. Conclusiones Los hallazgos apuntan a la necesidad de considerar intervenciones que se enfoquen en la prevención de VIH en mujeres, abordando los riesgos asociados al consumo de sustancias. PMID:21197380

  4. Hantaviruses in Africa.

    PubMed

    Witkowski, Peter T; Klempa, Boris; Ithete, Ndapewa L; Auste, Brita; Mfune, John K E; Hoveka, Julia; Matthee, Sonja; Preiser, Wolfgang; Kruger, Detlev H

    2014-07-17

    This paper summarizes the progress in the search for hantaviruses and hantavirus infections in Africa. After having collected molecular evidence of an indigenous African hantavirus in 2006, an intensive investigation for new hantaviruses has been started in small mammals. Various novel hantaviruses have been molecularly identified not only in rodents but also in shrews and bats. In addition, the first African hantavirus, Sangassou virus, has been isolated and functionally characterized in cell culture. Less is known about the ability of these hantaviruses to infect humans and to cause diseases. To date, no hantavirus genetic material could be amplified from patients' specimens collected in Africa. Serological studies in West Africa, based on a battery of screening and confirmatory assays, led to the detection of hantavirus antibodies in the human population and in patients with putative hantavirus disease. In addition to this overview, we present original data from seroepidemiological and field studies conducted in the Southern part of Africa. A human seroprevalence rate of 1.0% (n=1442) was detected in the South African Cape Region whereas no molecular evidence for the presence of hantavirus was found in 2500 small animals trapped in South Africa and Namibia. PMID:24406800

  5. Preventing Hantavirus Pulmonary Syndrome (HPS)

    MedlinePlus

    ... page: About CDC.gov . Hantavirus Share Compartir Preventing Hantavirus Pulmonary Syndrome (HPS) Eliminate or minimize contact with ... Pathogens Branch 1600 Clifton Rd Atlanta, GA 30333 Hantavirus Hotline (877) 232-3322 (404) 639-1510 800- ...

  6. Hantavirus Pulmonary Syndrome

    MedlinePlus

    ... get HPS? Rodents known to carry hantavirus include: Deer Mouse Cotton Rat Rice Rat White-Footed Mouse ... food that is easy to help reduce the population. to get to. More Information: For More Information ...

  7. Hantaviruses: a global disease problem.

    PubMed Central

    Schmaljohn, C.; Hjelle, B.

    1997-01-01

    Hantaviruses are carried by numerous rodent species throughout the world. In 1993, a previously unknown group of hantaviruses emerged in the United States as the cause of an acute respiratory disease now termed hantavirus pulmonary syndrome (HPS). Before than, hantaviruses were known as the etiologic agents of hemorrhagic fever with renal syndrome, a disease that occurs almost entirely in the Eastern Hemisphere. Since the discovery of the HPS-causing hantaviruses, intense investigation of the ecology and epidemiology of hantaviruses has led to the discovery of many other novel hantaviruses. Their ubiquity and potential for causing severe human illness make these viruses an important public health concern; we reviewed the distribution, ecology, disease potential, and genetic spectrum. PMID:9204290

  8. Diagnosing and Treating Hantavirus Pulmonary Syndrome (HPS)

    MedlinePlus

    ... CDC.gov . Hantavirus Share Compartir Diagnosing and Treating Hantavirus Pulmonary Syndrome (HPS) Diagnosing HPS Diagnosing HPS in ... of patients that develop HPS from New World Hantaviruses recover completely. No chronic infection has been detected ...

  9. How People Get Hantavirus Pulmonary Syndrome (HPS)

    MedlinePlus

    ... CDC.gov . Hantavirus Share Compartir How People Get Hantavirus Pulmonary Syndrome (HPS) Where HPS is Found Cases ... In the US and Canada, the Sin Nombre hantavirus is responsible for the majority of cases of ...

  10. Hantaviruses: Rediscovery and New Beginnings

    PubMed Central

    Yanagihara, Richard; Gu, Se Hun; Arai, Satoru; Kang, Hae Ji; Song, Jin-Won

    2014-01-01

    Virus and host gene phylogenies, indicating that antigenically distinct hantaviruses (family Bunyaviridae, genus Hantavirus) segregate into clades, which parallel the molecular evolution of rodents belonging to the Murinae, Arvicolinae, Neotominae and Sigmodontinae subfamilies, suggested co-divergence of hantaviruses and their rodent reservoirs. Lately, this concept has been vigorously contested in favor of preferential host switching and local host-specific adaptation. To gain insights into the host range, spatial and temporal distribution, genetic diversity and evolutionary origins of hantaviruses, we employed reverse transcription- polymerase chain reaction to analyze frozen, RNAlater®-preserved and ethanol-fixed tissues from 1,546 shrews (9 genera, 47 species), 281 moles (8 genera, 10 species) and 520 bats (26 genera and 53 species), collected in Europe, Asia, Africa and North America during 1980–2012. Thus far, we have identified 24 novel hantaviruses in shrews, moles and bats. That these newfound hantaviruses are geographically widespread and genetically more diverse than those harbored by rodents suggests that the evolutionary history of hantaviruses is far more complex than previously conjectured. Phylogenetic analyses indicate four distinct clades, with the most divergent comprising hantaviruses harbored by the European mole and insectivorous bats, with evidence for both co-divergence and host switching. Future studies will provide new knowledge about the transmission dynamics and pathogenic potential of these newly discovered, still-orphan, non-rodent-borne hantaviruses. PMID:24412714

  11. Hantaviruses: rediscovery and new beginnings.

    PubMed

    Yanagihara, Richard; Gu, Se Hun; Arai, Satoru; Kang, Hae Ji; Song, Jin-Won

    2014-07-17

    Virus and host gene phylogenies, indicating that antigenically distinct hantaviruses (family Bunyaviridae, genus Hantavirus) segregate into clades, which parallel the molecular evolution of rodents belonging to the Murinae, Arvicolinae, Neotominae and Sigmodontinae subfamilies, suggested co-divergence of hantaviruses and their rodent reservoirs. Lately, this concept has been vigorously contested in favor of preferential host switching and local host-specific adaptation. To gain insights into the host range, spatial and temporal distribution, genetic diversity and evolutionary origins of hantaviruses, we employed reverse transcription-polymerase chain reaction to analyze frozen, RNAlater(®)-preserved and ethanol-fixed tissues from 1546 shrews (9 genera and 47 species), 281 moles (8 genera and 10 species) and 520 bats (26 genera and 53 species), collected in Europe, Asia, Africa and North America during 1980-2012. Thus far, we have identified 24 novel hantaviruses in shrews, moles and bats. That these newfound hantaviruses are geographically widespread and genetically more diverse than those harbored by rodents suggests that the evolutionary history of hantaviruses is far more complex than previously conjectured. Phylogenetic analyses indicate four distinct clades, with the most divergent comprising hantaviruses harbored by the European mole and insectivorous bats, with evidence for both co-divergence and host switching. Future studies will provide new knowledge about the transmission dynamics and pathogenic potential of these newly discovered, still-orphan, non-rodent-borne hantaviruses. PMID:24412714

  12. Reported Cases of HPS (Hantavirus Pulmonary Syndrome)

    MedlinePlus

    ... message, please visit this page: About CDC.gov . Hantavirus Share Compartir Reported Cases of HPS HPS in ... 6, 2016, a total of 690 cases of Hantavirus Pulmonary Syndrome have been reported in the United ...

  13. Signs and Symptoms for Hantavirus Pulmonary Syndrome (HPS)

    MedlinePlus

    ... CDC.gov . Hantavirus Share Compartir Signs & Symptoms for Hantavirus Pulmonary Syndrome (HPS) Due to the small number ... Pathogens Branch 1600 Clifton Rd Atlanta, GA 30333 Hantavirus Hotline (877) 232-3322 (404) 639-1510 800- ...

  14. Conserved Endonuclease Function of Hantavirus L Polymerase.

    PubMed

    Rothenberger, Sylvia; Torriani, Giulia; Johansson, Maria U; Kunz, Stefan; Engler, Olivier

    2016-01-01

    Hantaviruses are important emerging pathogens belonging to the Bunyaviridae family. Like other segmented negative strand RNA viruses, the RNA-dependent RNA polymerase (RdRp) also known as L protein of hantaviruses lacks an intrinsic "capping activity". Hantaviruses therefore employ a "cap snatching" strategy acquiring short 5' RNA sequences bearing 5'cap structures by endonucleolytic cleavage from host cell transcripts. The viral endonuclease activity implicated in cap snatching of hantaviruses has been mapped to the N-terminal domain of the L protein. Using a combination of molecular modeling and structure-function analysis we confirm and extend these findings providing evidence for high conservation of the L endonuclease between Old and New World hantaviruses. Recombinant hantavirus L endonuclease showed catalytic activity and a defined cation preference shared by other viral endonucleases. Based on the previously reported remarkably high activity of hantavirus L endonuclease, we established a cell-based assay for the hantavirus endonuclase function. The robustness of the assay and its high-throughput compatible format makes it suitable for small molecule drug screens to identify novel inhibitors of hantavirus endonuclease. Based on the high degree of similarity to RdRp endonucleases, some candidate inhibitors may be broadly active against hantaviruses and other emerging human pathogenic Bunyaviruses. PMID:27144576

  15. Conserved Endonuclease Function of Hantavirus L Polymerase

    PubMed Central

    Rothenberger, Sylvia; Torriani, Giulia; Johansson, Maria U.; Kunz, Stefan; Engler, Olivier

    2016-01-01

    Hantaviruses are important emerging pathogens belonging to the Bunyaviridae family. Like other segmented negative strand RNA viruses, the RNA-dependent RNA polymerase (RdRp) also known as L protein of hantaviruses lacks an intrinsic “capping activity”. Hantaviruses therefore employ a “cap snatching” strategy acquiring short 5′ RNA sequences bearing 5′cap structures by endonucleolytic cleavage from host cell transcripts. The viral endonuclease activity implicated in cap snatching of hantaviruses has been mapped to the N-terminal domain of the L protein. Using a combination of molecular modeling and structure–function analysis we confirm and extend these findings providing evidence for high conservation of the L endonuclease between Old and New World hantaviruses. Recombinant hantavirus L endonuclease showed catalytic activity and a defined cation preference shared by other viral endonucleases. Based on the previously reported remarkably high activity of hantavirus L endonuclease, we established a cell-based assay for the hantavirus endonuclase function. The robustness of the assay and its high-throughput compatible format makes it suitable for small molecule drug screens to identify novel inhibitors of hantavirus endonuclease. Based on the high degree of similarity to RdRp endonucleases, some candidate inhibitors may be broadly active against hantaviruses and other emerging human pathogenic Bunyaviruses. PMID:27144576

  16. Detection of different South American hantaviruses.

    PubMed

    Guterres, Alexandro; de Oliveira, Renata Carvalho; Fernandes, Jorlan; Schrago, Carlos Guerra; de Lemos, Elba Regina Sampaio

    2015-12-01

    Hantaviruses are the etiologic agents of Hemorrhagic Fever with Renal Syndrome (HFRS) in Old World, and Hantavirus Pulmonary Syndrome (HPS)/Hantavirus Cardiopulmonary Syndrome (HCPS), in the New World. Serological methods are the most common approach used for laboratory diagnosis of HCPS, however theses methods do not allow the characterization of viral genotypes. The polymerase chain reaction (PCR) has been extensively used for diagnosis of viral infections, including those caused by hantaviruses, enabling detection of few target sequence copies in the sample. However, most studies proposed methods of PCR with species-specific primers. This study developed a simple and reliable diagnostic system by RT-PCR for different hantavirus detection. Using new primers set, we evaluated human and rodent hantavirus positive samples of various regions from Brazil. Besides, we performed computational analyzes to evaluate the detection of other South American hantaviruses. The diagnostic system by PCR proved to be a sensible and simple assay, allowing amplification of Juquitiba virus, Araraquara virus, Laguna Negra virus, Rio Mamore virus and Jabora virus, beyond of the possibility of the detecting Andes, Anajatuba, Bermejo, Choclo, Cano Delgadito, Lechiguanas, Maciel, Oran, Pergamino and Rio Mearim viruses. The primers sets designed in this study can detect hantaviruses from almost all known genetics lineages in Brazil and from others South America countries and also increases the possibility to detect new hantaviruses. These primers could easily be used both in diagnosis of suspected hantavirus infections in humans and also in studies with animals reservoirs. PMID:26220480

  17. Hantavirus in new geographic regions, Sweden

    PubMed Central

    Lõhmus, Mare; Verner-Carlsson, Jenny; Borg, Oliva; Albihn, Ann; Lundkvist, Åke

    2016-01-01

    In Sweden, human cases of Puumala hantavirus (PUUV) infections are reported from the northern endemic regions. We found hantavirus-specific antibodies in yellow-necked mice (Apodemus flavicollis) trapped in human dwellings in the surroundings of the cities of Uppsala and Stockholm, which are situated far south from the traditional endemic areas of PUUV. Because the yellow-necked mouse is the most common rodent in human dwellings, hantaviruses in this rodent species may be important for the public health. PMID:27258208

  18. Hantavirus in new geographic regions, Sweden.

    PubMed

    Lõhmus, Mare; Verner-Carlsson, Jenny; Borg, Oliva; Albihn, Ann; Lundkvist, Åke

    2016-01-01

    In Sweden, human cases of Puumala hantavirus (PUUV) infections are reported from the northern endemic regions. We found hantavirus-specific antibodies in yellow-necked mice (Apodemus flavicollis) trapped in human dwellings in the surroundings of the cities of Uppsala and Stockholm, which are situated far south from the traditional endemic areas of PUUV. Because the yellow-necked mouse is the most common rodent in human dwellings, hantaviruses in this rodent species may be important for the public health. PMID:27258208

  19. Hantavirus Infection in the Republic of Georgia

    PubMed Central

    Clark, Danielle V.; Hepburn, Matthew J.; Tsertsvadze, Tengiz; Pimentel, Guillermo; Imnadze, Paata

    2009-01-01

    We describe a laboratory-confirmed case of hantavirus infection in the Republic of Georgia. Limited information is available about hantavirus infections in the Caucasus, although the infection has been reported throughout Europe and Russia. Increasing awareness and active disease surveillance contribute to our improved understanding of the geographic range of this pathogen. PMID:19788822

  20. Human pathogenic hantaviruses and prevention of infection

    PubMed Central

    Schönrich, Günther; Klempa, Boris

    2011-01-01

    Hantaviruses are emerging viruses which are hosted by small mammals. When transmitted to humans, they can cause two clinical syndromes, hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. The review compiles the current list of hantaviruses which are thought to be pathogenic in humans on the basis of molecular or at least serological evidence. Whereas induction of a neutralizing humoral immune response is considered to be protective against infection, the dual role of cellular immunity (protection versus immunopathogenicity) is discussed. For immunization, inactivated virus vaccines are licensed in certain Asian countries. Moreover, several classical and molecular vaccine approaches are in pre-clinical stages of development. The development of hantavirus vaccines is hampered by the lack of adequate animal models of hantavirus-associated disease. In addition to active immunization strategies, the review summarizes other ways of infection prevention, as passive immunization, chemoprophylaxis and exposition prophylaxis. PMID:21508676

  1. High rates of molecular evolution in hantaviruses.

    PubMed

    Ramsden, Cadhla; Melo, Fernando L; Figueiredo, Luiz M; Holmes, Edward C; Zanotto, Paolo M A

    2008-07-01

    Hantaviruses are rodent-borne Bunyaviruses that infect the Arvicolinae, Murinae, and Sigmodontinae subfamilies of Muridae. The rate of molecular evolution in the hantaviruses has been previously estimated at approximately 10(-7) nucleotide substitutions per site, per year (substitutions/site/year), based on the assumption of codivergence and hence shared divergence times with their rodent hosts. If substantiated, this would make the hantaviruses among the slowest evolving of all RNA viruses. However, as hantaviruses replicate with an RNA-dependent RNA polymerase, with error rates in the region of one mutation per genome replication, this low rate of nucleotide substitution is anomalous. Here, we use a Bayesian coalescent approach to estimate the rate of nucleotide substitution from serially sampled gene sequence data for hantaviruses known to infect each of the 3 rodent subfamilies: Araraquara virus (Sigmodontinae), Dobrava virus (Murinae), Puumala virus (Arvicolinae), and Tula virus (Arvicolinae). Our results reveal that hantaviruses exhibit short-term substitution rates of 10(-2) to 10(-4) substitutions/site/year and so are within the range exhibited by other RNA viruses. The disparity between this substitution rate and that estimated assuming rodent-hantavirus codivergence suggests that the codivergence hypothesis may need to be reevaluated. PMID:18417484

  2. Reconstructing the evolutionary origins and phylogeography of hantaviruses

    PubMed Central

    Bennett, Shannon N.; Gu, Se Hun; Kang, Hae Ji; Arai, Satoru; Yanagihara, Richard

    2014-01-01

    Rodents have long been recognized as the principal reservoirs of hantaviruses. However, with the discovery of genetically distinct and phylogenetically divergent lineages of hantaviruses in multiple species of shrews, moles, and insectivorous bats from widely separated geographic regions, a far more complex landscape of hantavirus host distribution, evolution, and phylogeography is emerging. Detailed phylogenetic analyses, based on partial and full-length genomes of previously described rodent-borne hantaviruses and newly detected non-rodent-borne hantaviruses, indicate an Asian origin and support the emerging concept that ancestral non-rodent mammals may have served as the hosts of primordial hantaviruses. PMID:24852723

  3. [Human hantavirus diseases - still neglected zoonoses?].

    PubMed

    Vrbovská, V; Chalupa, P; Straková, P; Hubálek, Z; Rudolf, I

    2015-10-01

    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. PMID:26795222

  4. Molecular Evolution of Puumala Hantavirus

    PubMed Central

    Sironen, Tarja; Vaheri, Antti; Plyusnin, Alexander

    2001-01-01

    Puumala virus (PUUV) is a negative-stranded RNA virus in the genus Hantavirus, family Bunyaviridae. In this study, detailed phylogenetic analysis was performed on 42 complete S segment sequences of PUUV originated from several European countries, Russia, and Japan, the largest set available thus far for hantaviruses. The results show that PUUV sequences form seven distinct and well-supported genetic lineages; within these lineages, geographical clustering of genetic variants is observed. The overall phylogeny of PUUV is star-like, suggesting an early split of genetic lineages. The individual PUUV lineages appear to be independent, with the only exception to this being the Finnish and the Russian lineages that are closely connected to each other. Two strains of PUUV-like virus from Japan form the most ancestral lineage diverging from PUUV. Recombination points within the S segment were searched for and evidence for intralineage recombination events was seen in the Finnish, Russian, Danish, and Belgian lineages of PUUV. Molecular clock analysis showed that PUUV is a stable virus, evolving slowly at a rate of 0.7 × 10−7 to 2.2 × 10−6 nt substitutions per site per year. PMID:11689661

  5. Novel hantavirus identified in black-bearded tomb bats, China.

    PubMed

    Xu, Lin; Wu, Jianmin; He, Biao; Qin, Shaomin; Xia, Lele; Qin, Minchao; Li, Nan; Tu, Changchun

    2015-04-01

    Hantaviruses cause life-threatening diseases in human worldwide. Rodents, insectivores and bats are known hantaviral reservoirs, but lack of complete genomic sequences of bat-borne hantaviruses impedes phylogenetic and evolutionary comparison with those of rodents and insectivores. Here, a novel bat-borne hantavirus, Laibin virus (LBV), has been identified in a black-bearded tomb bat in China. The complete genomic sequence shows that LBV is only distantly related to all previously known bat-borne hantaviruses. PMID:25643870

  6. Discovery of hantaviruses and of the Hantavirus genus: personal and historical perspectives of the Presidents of the International Society of Hantaviruses.

    PubMed

    Lee, Ho Wang; Vaheri, Antti; Schmaljohn, Connie S

    2014-07-17

    We three authors, the two past presidents (HWL and AV) and the current president (CSS) of the International Society for Hantaviruses (ISH) have attended most of the nine International Conferences on HFRS, HPS and Hantaviruses (Table 1). These conferences have provided a forum for a synergistic group of clinicians, basic researchers, mammalogists, epidemiologists and ecologists to share their expertise and interests in all aspects of hantavirus research. Much of what is now hantavirus dogma was only conjecture when HWL organized the first conference in Seoul, Korea in 1989. Herein, we provide our reflections on key events in hantavirus research. As we come from distinct areas of the world and have had individual historical experiences, we certainly have our own geocentric opinions about the key events. Nevertheless, we agree that the discovery of hantaviruses has taken an interesting and unpredictable track to where we are today. PMID:24412711

  7. Hantavirus

    MedlinePlus

    ... if they breathe in contaminated dust from mice nests or droppings. You may come in contact with ... the building for another 30 minutes. Spray mouse nests and droppings with a 10% solution of chlorine ...

  8. Genetic detection of hantaviruses in rodents, Albania.

    PubMed

    Papa, Anna; Rogozi, Elton; Velo, Enkelejda; Papadimitriou, Evangelia; Bino, Silvia

    2016-08-01

    In order to have a first insight into the epidemiology of hantaviruses in Albania, 263 small mammals (248 rodents, 15 insectivores) were captured in 352 locations in 29 districts and tested for hantavirus infection. Dobrava-Belgrade virus (DOBV) was detected in 10 of 148 (6.7%) Apodemus flavicollis rodents. DOBV-positive A. flavicollis were detected in six districts (Diber, Korce, Kolonje, Librazhd, Pogradec, and Vlore). The obtained nucleotide sequences were highly similar to each other and to DOBV sequences from northwestern Greece. Understanding the epidemiology of hantaviruses and identifying the endemic foci enables the public health strategies to minimize the risk of human infection. J. Med. Virol. 88:1309-1313, 2016. © 2016 Wiley Periodicals, Inc. PMID:27249068

  9. Phylogenetic analysis of a newfound bat-borne hantavirus supports a laurasiatherian host association for ancestral mammalian hantaviruses.

    PubMed

    Witkowski, Peter T; Drexler, Jan F; Kallies, René; Ličková, Martina; Bokorová, Silvia; Mananga, Gael D; Szemes, Tomáš; Leroy, Eric M; Krüger, Detlev H; Drosten, Christian; Klempa, Boris

    2016-07-01

    Until recently, hantaviruses (family Bunyaviridae) were believed to originate from rodent reservoirs. However, genetically distinct hantaviruses were lately found in shrews and moles, as well as in bats from Africa and Asia. Bats (order Chiroptera) are considered important reservoir hosts for emerging human pathogens. Here, we report on the identification of a novel hantavirus, provisionally named Makokou virus (MAKV), in Noack's Roundleaf Bat (Hipposideros ruber) in Gabon, Central Africa. Phylogenetic analysis of the genomic l-segment showed that MAKV was the most closely related to other bat-borne hantaviruses and shared a most recent common ancestor with the Asian hantaviruses Xuan Son and Laibin. Breakdown of the virus load in a bat animal showed that MAKV resembles rodent-borne hantaviruses in its organ distribution in that it predominantly occurred in the spleen and kidney; this provides a first insight into the infection pattern of bat-borne hantaviruses. Ancestral state reconstruction based on a tree of l gene sequences of all relevant hantavirus lineages was combined with phylogenetic fossil host hypothesis testing, leading to a statistically significant rejection of the mammalian superorder Euarchontoglires (including rodents) but not the superorder Laurasiatheria (including shrews, moles, and bats) as potential hosts of ancestral hantaviruses at most basal tree nodes. Our data supports the emerging concept of bats as previously overlooked hantavirus reservoir hosts. PMID:27051047

  10. Hantaviral Proteins: Structure, Functions, and Role in Hantavirus Infection

    PubMed Central

    Muyangwa, Musalwa; Martynova, Ekaterina V.; Khaiboullina, Svetlana F.; Morzunov, Sergey P.; Rizvanov, Albert A.

    2015-01-01

    Hantaviruses are the members of the family Bunyaviridae that are naturally maintained in the populations of small mammals, mostly rodents. Most of these viruses can easily infect humans through contact with aerosols or dust generated by contaminated animal waste products. Depending on the particular Hantavirus involved, human infection could result in either hemorrhagic fever with renal syndrome or in Hantavirus cardiopulmonary syndrome. In the past few years, clinical cases of the Hantavirus caused diseases have been on the rise. Understanding structure of the Hantavirus genome and the functions of the key viral proteins are critical for the therapeutic agents’ research. This paper gives a brief overview of the current knowledge on the structure and properties of the Hantavirus nucleoprotein and the glycoproteins. PMID:26640463

  11. Interactions and Oligomerization of Hantavirus Glycoproteins▿

    PubMed Central

    Hepojoki, Jussi; Strandin, Tomas; Vaheri, Antti; Lankinen, Hilkka

    2010-01-01

    In this report the basis for the structural architecture of the envelope of hantaviruses, family Bunyaviridae, is systematically studied by the interactions of two glycoproteins N and C (Gn and Gc, respectively) and their respective disulfide bridge-mediated homo- and heteromeric oligomerizations. In virion extracts Gn and Gc associated in both homo- and hetero-oligomers which were, at least partially, thiol bridge mediated. Due to strong homo-oligomerization, the hetero-oligomers of Gn and Gc are likely to be mediated by homo-oligomeric subunits. A reversible pH-induced disappearance of a neutralizing epitope in Gc and dissociation of the Gn-Gc complex at pH values below 6.2 provide proteochemical evidence for the fusogenicity of Gc. Incomplete inactivation of virions at acidic pH indicates that additional factors are required for hantavirus fusion, as in the case of pestiviruses of the Flaviviridae. Based on similarities to class II fusion proteins, a structure model was created of hantavirus Gc using the Semliki Forest virus E1 protein as a template. In total, 10 binding regions for Gn were found by peptide scanning, of which five represent homotypic (GnI to GnV) and five represent heterotypic (GcI to GcV) interaction sites that we assign as intra- and interspike connections, respectively. In conclusion, the glycoprotein associations were compiled to a model wherein the surface of hantaviruses is formed of homotetrameric Gn complexes interconnected with Gc homodimers. This organization would create the grid-like surface pattern described earlier for hantaviruses in negatively stained electron microscopy specimens. PMID:19828613

  12. Differential Lymphocyte and Antibody Responses in Deer Mice Infected with Sin Nombre Hantavirus or Andes Hantavirus

    PubMed Central

    Quackenbush, Sandra; Rovnak, Joel; Haddock, Elaine; Black, William C.; Feldmann, Heinz; Prescott, Joseph

    2014-01-01

    ABSTRACT Hantavirus cardiopulmonary syndrome (HCPS) is a rodent-borne disease with a high case-fatality rate that is caused by several New World hantaviruses. Each pathogenic hantavirus is naturally hosted by a principal rodent species without conspicuous disease and infection is persistent, perhaps for life. Deer mice (Peromyscus maniculatus) are the natural reservoirs of Sin Nombre virus (SNV), the etiologic agent of most HCPS cases in North America. Deer mice remain infected despite a helper T cell response that leads to high-titer neutralizing antibodies. Deer mice are also susceptible to Andes hantavirus (ANDV), which causes most HCPS cases in South America; however, deer mice clear ANDV. We infected deer mice with SNV or ANDV to identify differences in host responses that might account for this differential outcome. SNV RNA levels were higher in the lungs but not different in the heart, spleen, or kidneys. Most ANDV-infected deer mice had seroconverted 14 days after inoculation, but none of the SNV-infected deer mice had. Examination of lymph node cell antigen recall responses identified elevated immune gene expression in deer mice infected with ANDV and suggested maturation toward a Th2 or T follicular helper phenotype in some ANDV-infected deer mice, including activation of the interleukin 4 (IL-4) pathway in T cells and B cells. These data suggest that the rate of maturation of the immune response is substantially higher and of greater magnitude during ANDV infection, and these differences may account for clearance of ANDV and persistence of SNV. IMPORTANCE Hantaviruses persistently infect their reservoir rodent hosts without pathology. It is unknown how these viruses evade sterilizing immune responses in the reservoirs. We have determined that infection of the deer mouse with its homologous hantavirus, Sin Nombre virus, results in low levels of immune gene expression in antigen-stimulated lymph node cells and a poor antibody response. However, infection

  13. Phylogenetic Relationship of Necoclí Virus to Other South American Hantaviruses (Bunyaviridae: Hantavirus)

    PubMed Central

    Montoya-Ruiz, Carolina; Cajimat, Maria N. B.; Milazzo, Mary Louise; Diaz, Francisco J.; Rodas, Juan David; Valbuena, Gustavo

    2015-01-01

    Abstract The results of a previous study suggested that Cherrie's cane rat (Zygodontomys cherriei) is the principal host of Necoclí virus (family Bunyaviridae, genus Hantavirus) in Colombia. Bayesian analyses of complete nucleocapsid protein gene sequences and complete glycoprotein precursor gene sequences in this study confirmed that Necoclí virus is phylogenetically closely related to Maporal virus, which is principally associated with the delicate pygmy rice rat (Oligoryzomys delicatus) in western Venezuela. In pairwise comparisons, nonidentities between the complete amino acid sequence of the nucleocapsid protein of Necoclí virus and the complete amino acid sequences of the nucleocapsid proteins of other hantaviruses were ≥8.7%. Likewise, nonidentities between the complete amino acid sequence of the glycoprotein precursor of Necoclí virus and the complete amino acid sequences of the glycoprotein precursors of other hantaviruses were ≥11.7%. Collectively, the unique association of Necoclí virus with Z. cherriei in Colombia, results of the Bayesian analyses of complete nucleocapsid protein gene sequences and complete glycoprotein precursor gene sequences, and results of the pairwise comparisons of amino acid sequences strongly support the notion that Necoclí virus represents a novel species in the genus Hantavirus. Further work is needed to determine whether Calabazo virus (a hantavirus associated with Z. brevicauda cherriei in Panama) and Necoclí virus are conspecific. PMID:26186516

  14. Spatial spread of the Hantavirus infection

    NASA Astrophysics Data System (ADS)

    Reinoso, José A.; de la Rubia, F. Javier

    2015-03-01

    The spatial propagation of Hantavirus-infected mice is considered a serious threat for public health. We analyze the spatial spread of the infected mice by including diffusion in the stage-dependent model for Hantavirus infection recently proposed by Reinoso and de la Rubia [Phys. Rev. E 87, 042706 (2013), 10.1103/PhysRevE.87.042706]. We consider a general scenario in which mice propagate in fronts from their refugia to the surroundings and find an expression for the speed of the front of infected mice. We also introduce a depletion time that measures the time scale for an appreciable impoverishment of the environment conditions and show how this new situation may change the spreading of the infection significantly.

  15. Spatial spread of the Hantavirus infection.

    PubMed

    Reinoso, José A; de la Rubia, F Javier

    2015-03-01

    The spatial propagation of Hantavirus-infected mice is considered a serious threat for public health. We analyze the spatial spread of the infected mice by including diffusion in the stage-dependent model for Hantavirus infection recently proposed by Reinoso and de la Rubia [Phys. Rev. E 87, 042706 (2013)]. We consider a general scenario in which mice propagate in fronts from their refugia to the surroundings and find an expression for the speed of the front of infected mice. We also introduce a depletion time that measures the time scale for an appreciable impoverishment of the environment conditions and show how this new situation may change the spreading of the infection significantly. PMID:25871140

  16. Outbreaks of Hantavirus induced by seasonality

    NASA Astrophysics Data System (ADS)

    Buceta, J.; Escudero, C.; de La Rubia, F. J.; Lindenberg, Katja

    2004-02-01

    Using a model for rodent population dynamics, we study outbreaks of Hantavirus infection induced by the alternation of seasons. Neither season by itself satisfies the environmental requirements for propagation of the disease. This result can be explained in terms of the seasonal interruption of the relaxation process of the mouse population toward equilibrium, and may shed light on the reported connection between climate variations and outbreaks of the disease.

  17. Spatiotemporal patterns in the Hantavirus infection

    NASA Astrophysics Data System (ADS)

    Abramson, G.; Kenkre, V. M.

    2002-07-01

    We present a model of the infection of Hantavirus in deer mouse, Peromyscus maniculatus, based on biological observations of the system in the North American Southwest. The results of the analysis shed light on relevant observations of the biological system, such as the sporadical disappearance of the infection, and the existence of foci or ``refugia'' that perform as reservoirs of the virus when environmental conditions are less than optimal.

  18. Risk Factors for Hantavirus Infection in Germany, 2005

    PubMed Central

    Abu Sin, Muna; Stark, Klaus; van Treeck, Ulrich; Dieckmann, Helga; Uphoff, Helmut; Hautmann, Wolfgang; Bornhofen, Bernhard; Jensen, Evelin; Pfaff, Günter

    2007-01-01

    In 2005, a marked increase in hantavirus infections was observed in Germany. Large cities and areas where hantaviruses were not known to be endemic were affected. A case–control study identified the following independent risk factors for infection: occupational exposure for construction workers, living <100 m from forested areas, and exposure to mice. PMID:18252110

  19. Dynamics of Hantavirus Infection in Peromyscus leucopus of Central Pennsylvania

    PubMed Central

    Vigliotti, Beth A.; Campbell, Shelley; Comer, James A.; Mills, James N.; Hudson, Peter J.

    2011-01-01

    Abstract Hantaviruses are distributed throughout the United States and are the etiologic agents for hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. Hantavirus genotypes and epidemiologic patterns vary spatially across the United States. While several longitudinal studies have been performed in the western United States, little is known about the virus in the eastern United States. We undertook a longitudinal study of hantaviruses in the primary rodent reservoir host in central Pennsylvania, Peromyscus leucopus. Prevalence of hantavirus antibodies varied both by year and site, but was not correlated with host abundance. Males were significantly more likely to have antibodies to a hantavirus than females, and both antibody sero-conversion and antibody prevalence increased with mass class (indicator for age). Our findings suggest that one or more hantaviruses are present and circulating among P. leucopus of central Pennsylvania, and understanding the dynamics in this region could help prevent zoonotic transmission to humans. Our aim was to describe the differences in epizootiology of hantavirus infection in rodents from various geographical locations to enable improved analysis of the risk of rodent-to-human transmission and obtain insights that may indicate improved means of disease intervention. PMID:21756028

  20. Hantavirus in northern short-tailed shrew, United States.

    PubMed

    Arai, Satoru; Song, Jin-Won; Sumibcay, Laarni; Bennett, Shannon N; Nerurkar, Vivek R; Parmenter, Cheryl; Cook, Joseph A; Yates, Terry L; Yanagihara, Richard

    2007-09-01

    Phylogenetic analyses, based on partial medium- and large-segment sequences, support an ancient evolutionary origin of a genetically distinct hantavirus detected by reverse transcription-PCR in tissues of northern short-tailed shrews (Blarina brevicauda) captured in Minnesota in August 1998. To our knowledge, this is the first evidence of hantaviruses harbored by shrews in the Americas. PMID:18252128

  1. Acute hantavirus infection induces galectin-3-binding protein.

    PubMed

    Hepojoki, Jussi; Strandin, Tomas; Hetzel, Udo; Sironen, Tarja; Klingström, Jonas; Sane, Jussi; Mäkelä, Satu; Mustonen, Jukka; Meri, Seppo; Lundkvist, Ake; Vapalahti, Olli; Lankinen, Hilkka; Vaheri, Antti

    2014-11-01

    Hantaviruses are zoonotic viruses that cause life-threatening diseases when transmitted to humans. Severe hantavirus infection is manifested by impairment of renal function, pulmonary oedema and capillary leakage. Both innate and adaptive immune responses contribute to the pathogenesis, but the underlying mechanisms are not fully understood. Here, we showed that galectin-3-binding protein (Gal-3BP) was upregulated as a result of hantavirus infection both in vitro and in vivo. Gal-3BP is a secreted glycoprotein found in human serum, and increased Gal-3BP levels have been reported in chronic viral infections and in several types of cancer. Our in vitro experiments showed that, whilst Vero E6 cells (an African green monkey kidney cell line) constitutively expressed and secreted Gal-3BP, this protein was detected in primary human cells only as a result of hantavirus infection. Analysis of Gal-3BP levels in serum samples of cynomolgus macaques infected experimentally with hantavirus indicated that hantavirus infection induced Gal-3BP also in vivo. Finally, analysis of plasma samples collected from patients hospitalized because of acute hantavirus infection showed higher Gal-3BP levels during the acute than the convalescent phase. Furthermore, the Gal-3BP levels in patients with haemorrhagic fever with renal syndrome correlated with increased complement activation and with clinical variables reflecting the severity of acute hantavirus infection. PMID:25013204

  2. Hantavirus in Indian Country: The First Decade in Review

    ERIC Educational Resources Information Center

    Pottinger, Richard

    2005-01-01

    Hantavirus, caused due to close contact with mice in a dwelling, first emerged in the spring of 1993 on the Navajo Reservation and although it is by no means an Indian disease, there are four times as many cases of hantavirus pulmonary syndrome (HPS) among non-Indians. Inadequate rural housing, especially common in western Indian Country,…

  3. Sympatry of 2 Hantavirus Strains, Paraguay, 2003–2007

    PubMed Central

    Chu, Yong-Kyu; Goodin, Douglas; Owen, Robert D.; Koch, David

    2009-01-01

    To explore geographic and host-taxonomic patterns of hantaviruses in Paraguay, we established sampling sites in the Mbaracayú Biosphere Reserve. We detected Jaborá virus and Itapúa37/Juquitiba–related virus in locations ≈20 m apart in different years, which suggested sympatry of 2 distinct hantaviruses. PMID:19961679

  4. Antigenic Properties of N Protein of Hantavirus

    PubMed Central

    Yoshimatsu, Kumiko; Arikawa, Jiro

    2014-01-01

    Hantavirus causes two important rodent-borne viral zoonoses, hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome (HPS) in North and South America. Twenty-four species that represent sero- and genotypes have been registered within the genus Hantavirus by the International Committee on Taxonomy of Viruses (ICTV). Among the viral proteins, nucleocapsid (N) protein possesses an immunodominant antigen. The antigenicitiy of N protein is conserved compared with that of envelope glycoproteins. Therefore, N protein has been used for serological diagnoses and seroepidemiological studies. An understanding of the antigenic properties of N protein is important for the interpretation of results from serological tests using N antigen. N protein consists of about 430 amino acids and possesses various epitopes. The N-terminal quarter of N protein bears linear and immunodominant epitopes. However, a serotype-specific and multimerization-dependent antigenic site was found in the C-terminal half of N protein. In this paper, the structure, function, and antigenicity of N protein are reviewed. PMID:25123683

  5. Clusters of Hantavirus Infection, Southern Argentina

    PubMed Central

    Cantoni, Gustavo E.; Calanni, Liliana M.; Resa, Amanda J.; Herrero, Eduardo R.; Iacono, Marisa A.; Enria, Delia A.; Cappa, Stella M. González

    2007-01-01

    Person-to-person transmission of a hantavirus was first confirmed during a 1996 outbreak of hantavirus pulmonary syndrome in southern Argentina, where Andes virus is endemic. To identify other episodes of secondary transmission, we reviewed reports of 51 hantavirus infection cases from this region (November 1993–June 2005). Nine clusters involving 20 cases (39.2%) were found. Two patients, who had symptoms 3 weeks after they shared risks for rodent exposure, were considered a cluster. The other 8 clusters each began with an index case, which was almost always fatal, followed 19–40 days later by the illness of >1 person who had close and prolonged contact with the index case-patient. Person-to-person transmission was considered the probable source of these 8 clusters. The probability of initiating secondary cases was 41% for patients who died versus 4% for those who survived (p = 0.005). Interpersonal transmission of Andes virus infection should be considered even when rodent exposure cannot be definitively excluded. PMID:17370522

  6. Hantavirus immunology of rodent reservoirs: current status and future directions.

    PubMed

    Schountz, Tony; Prescott, Joseph

    2014-01-01

    Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships. PMID:24638205

  7. Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions

    PubMed Central

    Schountz, Tony; Prescott, Joseph

    2014-01-01

    Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships. PMID:24638205

  8. Evidence of Hantavirus Infection among Bats in Brazil

    PubMed Central

    Sabino-Santos, Gilberto; Maia, Felipe Gonçalves Motta; Vieira, Thallyta Maria; de Lara Muylaert, Renata; Lima, Sabrina Miranda; Gonçalves, Cristieli Barros; Barroso, Patricia Doerl; Melo, Maria Norma; Jonsson, Colleen B.; Goodin, Douglas; Salazar-Bravo, Jorge; Figueiredo, Luiz Tadeu Moraes

    2015-01-01

    Hantaviruses are zoonotic viruses harbored by rodents, bats, and shrews. At present, only rodent-borne hantaviruses are associated with severe illness in humans. New species of hantaviruses have been recently identified in bats and shrews greatly expanding the potential reservoirs and ranges of these viruses. Brazil has one of the highest incidences of hantavirus cardiopulmonary syndrome in South America, hence it is critical to know what is the prevalence of hantaviruses in Brazil. Although much is known about rodent reservoirs, little is known regarding bats. We captured 270 bats from February 2012 to April 2014. Serum was screened for the presence of antibodies against a recombinant nucleoprotein (rN) of Araraquara virus (ARAQV). The prevalence of antibody to hantavirus was 9/53 with an overall seroprevalence of 17%. Previous studies have shown only insectivorous bats to harbor hantavirus; however, in our study, of the nine seropositive bats, five were frugivorous, one was carnivorous, and three were sanguivorous phyllostomid bats. PMID:26078322

  9. Evidence of Hantavirus Infection Among Bats in Brazil.

    PubMed

    Sabino-Santos, Gilberto; Maia, Felipe Gonçalves Motta; Vieira, Thallyta Maria; de Lara Muylaert, Renata; Lima, Sabrina Miranda; Gonçalves, Cristieli Barros; Barroso, Patricia Doerl; Melo, Maria Norma; Jonsson, Colleen B; Goodin, Douglas; Salazar-Bravo, Jorge; Figueiredo, Luiz Tadeu Moraes

    2015-08-01

    Hantaviruses are zoonotic viruses harbored by rodents, bats, and shrews. At present, only rodent-borne hantaviruses are associated with severe illness in humans. New species of hantaviruses have been recently identified in bats and shrews greatly expanding the potential reservoirs and ranges of these viruses. Brazil has one of the highest incidences of hantavirus cardiopulmonary syndrome in South America, hence it is critical to know what is the prevalence of hantaviruses in Brazil. Although much is known about rodent reservoirs, little is known regarding bats. We captured 270 bats from February 2012 to April 2014. Serum was screened for the presence of antibodies against a recombinant nucleoprotein (rN) of Araraquara virus (ARAQV). The prevalence of antibody to hantavirus was 9/53 with an overall seroprevalence of 17%. Previous studies have shown only insectivorous bats to harbor hantavirus; however, in our study, of the nine seropositive bats, five were frugivorous, one was carnivorous, and three were sanguivorous phyllostomid bats. PMID:26078322

  10. Potential Geographic Distribution of Hantavirus Reservoirs in Brazil

    PubMed Central

    de Oliveira, Stefan Vilges; Escobar, Luis E.; Peterson, A. Townsend; Gurgel-Gonçalves, Rodrigo

    2013-01-01

    Hantavirus cardiopulmonary syndrome is an emerging zoonosis in Brazil. Human infections occur via inhalation of aerosolized viral particles from excreta of infected wild rodents. Necromys lasiurus and Oligoryzomys nigripes appear to be the main reservoirs of hantavirus in the Atlantic Forest and Cerrado biomes. We estimated and compared ecological niches of the two rodent species, and analyzed environmental factors influencing their occurrence, to understand the geography of hantavirus transmission. N. lasiurus showed a wide potential distribution in Brazil, in the Cerrado, Caatinga, and Atlantic Forest biomes. Highest climate suitability for O. nigripes was observed along the Brazilian Atlantic coast. Maximum temperature in the warmest months and annual precipitation were the variables that most influence the distributions of N. lasiurus and O. nigripes, respectively. Models based on occurrences of infected rodents estimated a broader area of risk for hantavirus transmission in southeastern and southern Brazil, coinciding with the distribution of human cases of hantavirus cardiopulmonary syndrome. We found no demonstrable environmental differences among occurrence sites for the rodents and for human cases of hantavirus. However, areas of northern and northeastern Brazil are also apparently suitable for the two species, without broad coincidence with human cases. Modeling of niches and distributions of rodent reservoirs indicates potential for transmission of hantavirus across virtually all of Brazil outside the Amazon Basin. PMID:24391989

  11. Shared Ancestry between a Newfound Mole-Borne Hantavirus and Hantaviruses Harbored by Cricetid Rodents ▿†

    PubMed Central

    Kang, Hae Ji; Bennett, Shannon N.; Hope, Andrew G.; Cook, Joseph A.; Yanagihara, Richard

    2011-01-01

    Discovery of genetically distinct hantaviruses in multiple species of shrews (order Soricomorpha, family Soricidae) and moles (family Talpidae) contests the conventional view that rodents (order Rodentia, families Muridae and Cricetidae) are the principal reservoir hosts and suggests that the evolutionary history of hantaviruses is far more complex than previously hypothesized. We now report on Rockport virus (RKPV), a hantavirus identified in archival tissues of the eastern mole (Scalopus aquaticus) collected in Rockport, TX, in 1986. Pairwise comparison of the full-length S, M, and L genomic segments indicated moderately low sequence similarity between RKPV and other soricomorph-borne hantaviruses. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that RKPV shared a most recent common ancestor with cricetid-rodent-borne hantaviruses. Distributed widely across the eastern United States, the fossorial eastern mole is sympatric and syntopic with cricetid rodents known to harbor hantaviruses, raising the possibility of host-switching events in the distant past. Our findings warrant more-detailed investigations on the dynamics of spillover and cross-species transmission of present-day hantaviruses within communities of rodents and moles. PMID:21632770

  12. Cardiopulmonary involvement in Puumala hantavirus infection

    PubMed Central

    2013-01-01

    Background Hantavirus infections cause potentially life-threatening disease in humans world-wide. Infections with American hantaviruses may lead to hantavirus pulmonary syndrome characterised by severe cardiopulmonary distress with high mortality. Pulmonary involvement in European Puumala hantavirus (PUUV) infection has been reported, whereas knowledge of potential cardiac manifestations is limited. We aimed to comprehensively investigate cardiopulmonary involvement in patients with PUUV-infection. Methods Twenty-seven hospitalised patients with PUUV-infection were examined with lung function tests, chest high-resolution CT (HRCT), echocardiography including speckle tracking strain rate analysis, ECG and measurements of cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-ProBNP) and troponin T. Patients were re-evaluated after 3 months. Twenty-five age and sex-matched volunteers acted as controls for echocardiography data. Results Two-thirds of the patients experienced respiratory symptoms as dry cough or dyspnoea. Gas diffusing capacity was impaired in most patients, significantly improving at follow-up but still subnormal in 38%. HRCT showed thoracic effusions or pulmonary oedema in 46% of the patients. Compared to controls, the main echocardiographic findings in patients during the acute phase were significantly higher pulmonary vascular resistance, higher systolic pulmonary artery pressure, lower left ventricular ejection fraction and impaired left atrial myocardial motion. Pathological ECG, atrial fibrillation or T-wave changes, was demonstrated in 26% of patients. NT-ProBNP concentrations were markedly increased and were inversely associated with gas diffusing capacity but positively correlated to pulmonary vascular resistance. Furthermore, patients experiencing impaired general condition at follow-up had significantly lower gas diffusing capacity and higher pulmonary vascular resistance, compared to those feeling fully recovered. Conclusions In

  13. Hantavirus Infection in Humans and Rodents, Northwestern Argentina

    PubMed Central

    Levis, Silvana; Calderón, Gladys; Ramirez, Josefina; Bravo, Daniel; Lozano, Elena; Ripoll, Carlos; St. Jeor, Stephen; Ksiazek, Thomas G.; Barquez, Ruben M.; Enria, Delia

    2003-01-01

    We initiated a study to elucidate the ecology and epidemiology of hantavirus infections in northern Argentina. The northwestern hantavirus pulmonary syndrome (HPS)–endemic area of Argentina comprises Salta and Jujuy Provinces. Between 1997 and 2000, 30 HPS cases were diagnosed in Jujuy Province (population 512,329). Most patients had a mild clinical course, and the death rate (13.3%) was low. We performed a serologic and epidemiologic survey in residents of the area, in conjunction with a serologic study in rodents. The prevalence of hantavirus antibodies in the general human population was 6.5%, one of the highest reported in the literature. No evidence of interhuman transmission was found, and the high prevalence of hantavirus antibody seemed to be associated with the high infestation of rodents detected in domestic and peridomestic habitats. PMID:14519242

  14. Hantavirus reservoir hosts associated with peridomestic habitats in Argentina.

    PubMed Central

    Calderón, G.; Pini, N.; Bolpe, J.; Levis, S.; Mills, J.; Segura, E.; Guthmann, N.; Cantoni, G.; Becker, J.; Fonollat, A.; Ripoll, C.; Bortman, M.; Benedetti, R.; Enria, D.

    1999-01-01

    Five species of sigmodontine rodents have been identified in Argentina as the putative reservoirs of six circulating hantavirus genotypes. Two species of Oligoryzomys are associated with the genotypes causing hantavirus pulmonary syndrome, Oligoryzomys flavescens for Lechiguanas and O. longicaudatus for Andes and Oran genotypes. Reports of human cases of hantavirus pulmonary syndrome prompted rodent trapping (2,299 rodents of 32 species during 27,780 trap nights) at potential exposure sites in three disease-endemic areas. Antibody reactive to Sin Nombre virus was found in six species, including the known hantavirus reservoir species. Risk for peridomestic exposure to host species that carry recognized human pathogens was high in all three major disease-endemic areas. PMID:10603213

  15. Biological control agents elevate hantavirus by subsidizing deer mouse populations.

    PubMed

    Pearson, Dean E; Callaway, Ragan M

    2006-04-01

    Biological control of exotic invasive plants using exotic insects is practiced under the assumption that biological control agents are safe if they do not directly attack non-target species. We tested this assumption by evaluating the potential for two host-specific biological control agents (Urophora spp.), widely established in North America for spotted knapweed (Centaurea maculosa) control, to indirectly elevate Sin Nombre hantavirus by providing food subsidies to populations of deer mice (Peromyscus maniculatus), the primary reservoir for the virus. We show that seropositive deer mice (mice testing positive for hantavirus) were over three times more abundant in the presence of the biocontrol food subsidy. Elevating densities of seropositive mice may increase risk of hantavirus infection in humans and significantly alter hantavirus ecology. Host specificity alone does not ensure safe biological control. To minimize indirect risks to non-target species, biological control agents must suppress pest populations enough to reduce their own numbers. PMID:16623730

  16. Recent Evidence of Hantavirus Circulation in the American Tropic

    PubMed Central

    Montoya-Ruiz, Carolina; Diaz, Francisco J.; Rodas, Juan D.

    2014-01-01

    Hantaan virus was discovered in Korea during the 1970s while other similar viruses were later reported in Asia and Europe. There was no information about hantavirus human infection in the Americas until 1993 when an outbreak was described in the United States. This event promoted new studies to find hantaviruses in the Americas. At first, many studies were conducted in Brazil, Argentina, Chile, Uruguay and Paraguay, while other Latin American countries began to report the presence of these agents towards the end of the 20th century. More than 30 hantaviruses have been reported in the Western Hemisphere with more frequent cases registered in the southern cone (Argentina, Chile, Uruguay, Paraguay, Bolivia and Brazil). However there was an important outbreak in 2000 in Panama and some rare events have been described in Peru, Venezuela and French Guiana. Since hantaviruses have only recently emerged as a potential threat in the tropical zones of the Americas, this review compiles recent hantavirus reports in Central America, the Caribbean islands and the northern region of South America. These studies have generated the discovery of new hantaviruses and could help to anticipate the presentation of possible future outbreaks in the region. PMID:24638203

  17. Hantavirus Infection Prevalence in Wild Rodents and Human Anti-Hantavirus Serological Profiles from Different Geographic Areas of South Brazil

    PubMed Central

    Raboni, Sonia M.; Delfraro, Adriana; de Borba, Luana; Teixeira, Bernardo R.; Stella, Vanessa; de Araujo, Marina R.; Carstensen, Suzana; Rubio, Giselia; Maron, Angela; Lemos, Elba R. S.; D'Andrea, Paulo S.; Duarte dos Santos, Claudia N.

    2012-01-01

    Paraná state presents the fourth highest number of accumulated cases of hantavirus pulmonary syndrome in Brazil. To map the risk areas for hantavirus transmission we carried out a study based on rodent trapping and determined the anti-hantavirus seroprevalence in these animals and in the inhabitants of these localities. Overall seroprevalence in rodents and humans were 2.5% and 2.4%, respectively. Eighty-two percent of the seropositive rodents were genetically analyzed. Phylogenetic analyses revealed that hantaviruses from rodent samples cluster with Araucária (Juquitiba-like) or Jaborá hantavirus genotypes. The Jaborá strain was identified in Akodon serrensis and Akodon montensis, whereas the Araucária strain was detected in Oligoryzomys nigripes, Oxymycterus judex, A. montensis, and Akodon paranaensis, with the latter species being identified for the first time as a natural host. These findings expose the complex relationships between virus and reservoirs in Brazil, which could have an impact on hantavirus transmission dynamics in nature and human epidemiology. PMID:22855773

  18. Outbreak of Hantavirus Pulmonary Syndrome, Los Santos, Panama, 1999–2000

    PubMed Central

    Bayard, Vicente; Barria, Eduardo O.; Ruedas, Luis A.; Tinnin, David S.; Muñoz, Carlos; de Mosca, Itza B.; Guerrero, Gladys; Kant, Rudick; Garcia, Arsenio; Caceres, Lorenzo; Gracia, Fernando G.; Quiroz, Evelia; de Castillo, Zoila; Armien, Blas; Libel, Marlo; Mills, James N.; Khan, Ali S.; Nichol, Stuart T.; Rollin, Pierre E.; Ksiazek, Thomas G.; Peters, Clarence J.

    2004-01-01

    An outbreak of hantavirus pulmonary syndrome occurred in the province of Los Santos, Panama, in late 1999 and early 2000. Eleven cases were identified; 9 were confirmed by serology. Three cases were fatal; however, no confirmed case-patient died. Case-neighborhood serologic surveys resulted in an overall hantavirus antibody prevalence of 13% among household and neighborhood members from the outbreak foci. Epidemiologic investigations did not suggest person-to-person transmission of hantavirus infection. By use of Sin Nombre virus antigen, hantavirus antibodies were detected in Oligoryzomys fulvescens and Zygodontomys brevicauda cherriei. This outbreak resulted in the first documented cases of human hantavirus infections in Central America. PMID:15498167

  19. Hantavirus Prevalence in the IX Region of Chile

    PubMed Central

    Vial, Pablo C.; Castillo, Constanza H.; Godoy, Paula M.; Hjelle, Brian; Ferrés, Marcela G.

    2003-01-01

    An epidemiologic and seroprevalence survey was conducted (n=830) to assess proportion of persons exposed to hantavirus in IX Region Chile, which accounts for 25% of reported cases of hantavirus cardiopulmonary syndrome. This region has three geographic areas with different disease incidences and a high proportion of aboriginals. Serum samples were tested for immunoglobulin (Ig) G antibodies by enzyme-linked immunosorbent assay against Sin Nombre virus N antigen by strip immunoblot assay against Sin Nombre, Puumala, Río Mamoré, and Seoul N antigens. Samples from six patients were positive for IgG antibodies reactive with Andes virus; all patients lived in the Andes Mountains. Foresting was also associated with seropositivity; but not sex, age, race, rodent exposure, or farming activities. Exposure to hantavirus varies in different communities of IX Region. Absence of history of pneumonia or hospital admission in persons with specific IgG antibodies suggests that infection is clinically inapparent. PMID:12890323

  20. Hantavirus cardiopulmonary syndrome successfully treated with high-volume hemofiltration.

    PubMed

    Bugedo, Guillermo; Florez, Jorge; Ferres, Marcela; Roessler, Eric; Bruhn, Alejandro

    2016-06-01

    Hantavirus cardiopulmonary syndrome has a high mortality rate, and early connection to extracorporeal membrane oxygenation has been suggested to improve outcomes. We report the case of a patient with demonstrated Hantavirus cardiopulmonary syndrome and refractory shock who fulfilled the criteria for extracorporeal membrane oxygenation and responded successfully to high volume continuous hemofiltration. The implementation of high volume continuous hemofiltration along with protective ventilation reversed the shock within a few hours and may have prompted recovery. In patients with Hantavirus cardiopulmonary syndrome, a short course of high volume continuous hemofiltration may help differentiate patients who can be treated with conventional intensive care unit management from those who will require more complex therapies, such as extracorporeal membrane oxygenation. PMID:27410413

  1. Hantavirus cardiopulmonary syndrome successfully treated with high-volume hemofiltration

    PubMed Central

    Bugedo, Guillermo; Florez, Jorge; Ferres, Marcela; Roessler, Eric; Bruhn, Alejandro

    2016-01-01

    Hantavirus cardiopulmonary syndrome has a high mortality rate, and early connection to extracorporeal membrane oxygenation has been suggested to improve outcomes. We report the case of a patient with demonstrated Hantavirus cardiopulmonary syndrome and refractory shock who fulfilled the criteria for extracorporeal membrane oxygenation and responded successfully to high volume continuous hemofiltration. The implementation of high volume continuous hemofiltration along with protective ventilation reversed the shock within a few hours and may have prompted recovery. In patients with Hantavirus cardiopulmonary syndrome, a short course of high volume continuous hemofiltration may help differentiate patients who can be treated with conventional intensive care unit management from those who will require more complex therapies, such as extracorporeal membrane oxygenation. PMID:27410413

  2. Isolation and Characterization of a Hantavirus from Lemmus sibiricus: Evidence for Host Switch during Hantavirus Evolution

    PubMed Central

    Vapalahti, Olli; Lundkvist, Åke; Fedorov, Vadim; Conroy, Christopher J.; Hirvonen, Sirpa; Plyusnina, Angelina; Nemirov, Kirill; Fredga, Karl; Cook, Joseph A.; Niemimaa, Jukka; Kaikusalo, Asko; Henttonen, Heikki; Vaheri, Antti; Plyusnin, Alexander

    1999-01-01

    A novel hantavirus, first detected in Siberian lemmings (Lemmus sibiricus) collected near the Topografov River in the Taymyr Peninsula, Siberia (A. Plyusnin et al., Lancet 347:1835–1836, 1996), was isolated in Vero E6 cells and in laboratory-bred Norwegian lemmings (Lemmus lemmus). The virus, named Topografov virus (TOP), was most closely related to Khabarovsk virus (KBR) and Puumala viruses (PUU). In a cross focus reduction neutralization test, anti-TOP Lemmus antisera showed titers at least fourfold higher with TOP than with other hantaviruses; however, a rabbit anti-KBR antiserum neutralized TOP and KBR at the same titer. The TOP M segment showed 77% nucleotide and 88% amino acid identity with KBR and 76% nucleotide and 82% amino acid identity with PUU. However, the homology between TOP and the KBR S segment was disproportionately higher: 88% at the nucleotide level and 96% at the amino acid level. The 3′ noncoding regions of KBR and the TOP S and M segments were alignable except for 113- and 58-nucleotide deletions in KBR. The phylogenetic relationships of TOP, KBR, and PUU and their respective rodent carriers suggest that an exceptional host switch took place during the evolution of these viruses; while TOP and KBR are monophyletic, the respective rodent host species are only distantly related. PMID:10364307

  3. Experimental infection of Rio Mamore hantavirus in Sigmodontinae rodents.

    PubMed

    Souza, William Marciel de; Machado, Alex Martins; Figueiredo, Luiz Tadeu Moraes

    2016-05-24

    This study shows an experimental spillover infection of Sigmodontinae rodents with Rio Mamore hantavirus (RIOMV). Necromys lasiurus and Akodon sp were infected with 103 RNA copies of RIOMV by intraperitoneal administration. The viral genome was detected in heart, lung, and kidney tissues 18 days after infection (ai), and viral excretion in urine and faeces began at four and six ai, respectively. These results reveal that urine and faeces of infected rodents contain the virus for at least 18 days. It is possible that inhaled aerosols of these excreta could transmit hantavirus to humans and other animals. PMID:27223653

  4. Experimental infection of Rio Mamore hantavirus in Sigmodontinae rodents

    PubMed Central

    de Souza, William Marciel; Machado, Alex Martins; Figueiredo, Luiz Tadeu Moraes

    2016-01-01

    This study shows an experimental spillover infection ofSigmodontinae rodents with Rio Mamore hantavirus (RIOMV).Necromys lasiurus and Akodon sp were infected with 103 RNA copies of RIOMV by intraperitoneal administration. The viral genome was detected in heart, lung, and kidney tissues 18 days after infection (ai), and viral excretion in urine and faeces began at four and six ai, respectively. These results reveal that urine and faeces of infected rodents contain the virus for at least 18 days. It is possible that inhaled aerosols of these excreta could transmit hantavirus to humans and other animals. PMID:27223653

  5. Genetic characterization of hantaviruses associated with sigmodontine rodents in an endemic area for hantavirus pulmonary syndrome in southern Brazil.

    PubMed

    de Oliveira, Renata Carvalho; Padula, Paula J; Gomes, Raphael; Martinez, Valeria P; Bellomo, Carla; Bonvicino, Cibele R; Freire e Lima, Danúbia Inês; Bragagnolo, Camila; Caldas, Antônio C S; D'Andrea, Paulo S; de Lemos, Elba R S

    2011-03-01

    An ecological assessment of reservoir species was conducted in a rural area (Jaborá) in the mid-west of the state of Santa Catarina in southern Brazil, where hantavirus pulmonary syndrome is endemic, to evaluate the prevalence of hantavirus infection in wild rodents. Blood and tissue samples were collected from 507 rodents during seven field trips from March 2004 to April 2006. Some of the animals were karyotyped to confirm morphological identification. Phylogenetic reconstructions of rodent specimens, based on the mitochondrial DNA cytochrome b gene sequences, were also obtained. Hantavirus antibody was found in 22 (4.3%) of the 507 rodents: 5 Akodon montensis, 2 Akodon paranaensis, 14 Oligoryzomys nigripes, and 1 Sooretamys angouya. Viral RNAs detected in O. nigripes and A. montensis were amplified and sequenced. O. nigripes virus genome was 97.5% (nt) and 98.4% (nt) identical to sequences published for Araucaria (Juquitiba-like) virus based on N and G2 fragment sequences. Viral sequences from A. montensis strain showed 89% and 88% nucleotide identities in a 905-nt fragment of the nucleocapsid (N) protein-coding region of the S segment when it was compared with two other Akodontine rodent-associated viruses from Paraguay, A. montensis and Akodon cursor, respectively. Phylogenetic analysis showed the cocirculation of two genetic hantavirus lineages in the state of Santa Catarina, one from O. nigripes and the other from A. montensis, previously characterized in Brazil and Paraguay, respectively. The hantavirus associated with A. montensis, designed Jaborá virus, represents a distinct phylogenetic lineage among the Brazilian hantaviruses. PMID:21138380

  6. High genetic structuring of Tula hantavirus.

    PubMed

    Schmidt, Sabrina; Saxenhofer, Moritz; Drewes, Stephan; Schlegel, Mathias; Wanka, Konrad M; Frank, Raphael; Klimpel, Sven; von Blanckenhagen, Felix; Maaz, Denny; Herden, Christiane; Freise, Jona; Wolf, Ronny; Stubbe, Michael; Borkenhagen, Peter; Ansorge, Hermann; Eccard, Jana A; Lang, Johannes; Jourdain, Elsa; Jacob, Jens; Marianneau, Philippe; Heckel, Gerald; Ulrich, Rainer G

    2016-05-01

    Tula virus (TULV) is a vole-associated hantavirus with low or no pathogenicity to humans. In the present study, 686 common voles (Microtus arvalis), 249 field voles (Microtus agrestis) and 30 water voles (Arvicola spec.) were collected at 79 sites in Germany, Luxembourg and France and screened by RT-PCR and TULV-IgG ELISA. TULV-specific RNA and/or antibodies were detected at 43 of the sites, demonstrating a geographically widespread distribution of the virus in the studied area. The TULV prevalence in common voles (16.7 %) was higher than that in field voles (9.2 %) and water voles (10.0 %). Time series data at ten trapping sites showed evidence of a lasting presence of TULV RNA within common vole populations for up to 34 months, although usually at low prevalence. Phylogenetic analysis demonstrated a strong genetic structuring of TULV sequences according to geography and independent of the rodent species, confirming the common vole as the preferential host, with spillover infections to co-occurring field and water voles. TULV phylogenetic clades showed a general association with evolutionary lineages in the common vole as assessed by mitochondrial DNA sequences on a large geographical scale, but with local-scale discrepancies in the contact areas. PMID:26831932

  7. Evolutionary Insights from a Genetically Divergent Hantavirus Harbored by the European Common Mole (Talpa europaea)

    PubMed Central

    Kang, Hae Ji; Bennett, Shannon N.; Sumibcay, Laarni; Arai, Satoru; Hope, Andrew G.; Mocz, Gabor; Song, Jin-Won; Cook, Joseph A.; Yanagihara, Richard

    2009-01-01

    Background The discovery of genetically distinct hantaviruses in shrews (Order Soricomorpha, Family Soricidae) from widely separated geographic regions challenges the hypothesis that rodents (Order Rodentia, Family Muridae and Cricetidae) are the primordial reservoir hosts of hantaviruses and also predicts that other soricomorphs harbor hantaviruses. Recently, novel hantavirus genomes have been detected in moles of the Family Talpidae, including the Japanese shrew mole (Urotrichus talpoides) and American shrew mole (Neurotrichus gibbsii). We present new insights into the evolutionary history of hantaviruses gained from a highly divergent hantavirus, designated Nova virus (NVAV), identified in the European common mole (Talpa europaea) captured in Hungary. Methodology/Principal Findings Pair-wise alignment and comparison of the full-length S- and L-genomic segments indicated moderately low sequence similarity of 54–65% and 46–63% at the nucleotide and amino acid levels, respectively, between NVAV and representative rodent- and soricid-borne hantaviruses. Despite the high degree of sequence divergence, the predicted secondary structure of the NVAV nucleocapsid protein exhibited the characteristic coiled-coil domains at the amino-terminal end, and the L-segment motifs, typically found in hantaviruses, were well conserved. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that NVAV formed a distinct clade that was evolutionarily distant from all other hantaviruses. Conclusions Newly identified hantaviruses harbored by shrews and moles support long-standing virus-host relationships and suggest that ancestral soricomorphs, rather than rodents, may have been the early or original mammalian hosts. PMID:19582155

  8. Viral load of patients with hantavirus pulmonary syndrome in Argentina.

    PubMed

    Bellomo, Carla María; Pires-Marczeski, Fanny Clara; Padula, Paula Julieta

    2015-11-01

    Hantavirus causes severe illness including pneumonia, which leads to hospitalization and often death. At present, there is no specific treatment available. The hantavirus pathogenesis is not well understood, but most likely both virus-mediated and host-mediated mechanisms, are involved. The aim of this study was to correlate viral load in samples of hantavirus pulmonary syndrome cases and hantavirus infected individuals, with clinical epidemiological parameters and disease outcome. The variables that could potentially be related with viral load were analyzed. The retrospective study included 73 cases or household contacts, with different clinical evolution. Viral load was measured by reverse-transcription and real time polymerase chain reaction. There was no statistically significant association between blood viral RNA levels and severity of disease. However, viral load was inversely correlated with IgG response in a statistically significant manner. The level of viral RNA was significantly higher in patients infected with Andes virus South lineage, and was markedly low in persons infected with Laguna Negra virus. These results suggest that the infecting viral genotype is associated with disease severity, and that high viral load is associated with a low specific IgG response. Sex, age and disease severity were not related with viral load. Further investigations increasing strikingly the number of cases and also limiting the variables to be studied are necessary. PMID:26087934

  9. Reporting Hantavirus: A Study of Intercultural Environmental Journalism.

    ERIC Educational Resources Information Center

    Valenti, JoAnn M.

    A study examined media coverage of hantavirus in three Southwestern regional newspapers, including interviews with journalists and sources involved in the coverage, and implications of the media's portrayal of Navajo culture. Content review of regional coverage--67 articles in three regional newspapers were reviewed in the first year of a new…

  10. Population Ecology of Hantavirus Rodent Hosts in Southern Brazil

    PubMed Central

    Teixeira, Bernardo R.; Loureiro, Nathalie; Strecht, Liana; Gentile, Rosana; Oliveira, Renata C.; Guterres, Alexandro; Fernandes, Jorlan; Mattos, Luciana H. B. V.; Raboni, Sonia M.; Rubio, Giselia; Bonvicino, Cibele R.; Duarte dos Santos, Claudia N.; Lemos, Elba R. S.; D'Andrea, Paulo S.

    2014-01-01

    In this study we analyze population dynamics of hantavirus rodent hosts and prevalence of infection over a 2-year period in Southern Brazil, a region with a high incidence of hantavirus pulmonary syndrome. The 14 small mammal species captured were composed of 10 rodents and four marsupials, the six most abundant species being Akodon serrensis, Oxymycterus judex, Akodon montensis, Akodon paranaensis, Oligoryzomys nigripes, and Thaptomys nigrita. These species displayed a similar pattern with increasing population sizes in fall/winter caused by recruitment and both, increase in reproductive activity and higher hantavirus prevalence in spring/summer. Specific associations between A. montensis/Jaborá Virus (JABV) and O. nigripes/Juquitiba-like Virus (JUQV-like) and spillover infections between A. paranaensis/JABV, A. serrensis/JABV, and A. paranaensis/JUQV-like were observed. Spillover infection in secondary hosts seems to play an important role in maintaining JABV and JUQV-like in the hantavirus sylvatic cycle mainly during periods of low prevalence in primary hosts. PMID:24935954

  11. Hantaviruses in the Americas and Their Role as Emerging Pathogens

    PubMed Central

    Hjelle, Brian; Torres-Pérez, Fernando

    2010-01-01

    The continued emergence and re-emergence of pathogens represent an ongoing, sometimes major, threat to populations. Hantaviruses (family Bunyaviridae) and their associated human diseases were considered to be confined to Eurasia, but the occurrence of an outbreak in 1993–94 in the southwestern United States led to a great increase in their study among virologists worldwide. Well over 40 hantaviral genotypes have been described, the large majority since 1993, and nearly half of them pathogenic for humans. Hantaviruses cause persistent infections in their reservoir hosts, and in the Americas, human disease is manifest as a cardiopulmonary compromise, hantavirus cardiopulmonary syndrome (HCPS), with case-fatality ratios, for the most common viral serotypes, between 30% and 40%. Habitat disturbance and larger-scale ecological disturbances, perhaps including climate change, are among the factors that may have increased the human caseload of HCPS between 1993 and the present. We consider here the features that influence the structure of host population dynamics that may lead to viral outbreaks, as well as the macromolecular determinants of hantaviruses that have been regarded as having potential contribution to pathogenicity. PMID:21994631

  12. Hantavirus nephropathy as a pseudo-import pathology from Ecuador.

    PubMed

    Demeester, R; Bottieau, E; Van Esbroeck, M; Pourkarim, M R; Maes, P; Clement, J

    2010-01-01

    We report a case of hantavirus infection (nephropathia epidemica) diagnosed in a Belgian backpacker returning from a trekking expedition in Ecuador, after likely heavy exposure to rodents. Because of epidemiological inconsistency, molecular investigation was performed and revealed a Puumala infection acquired during very limited exposure in Belgium upon return. PMID:19821128

  13. Hantavirus Pulmonary Syndrome, Central Plateau, Southeastern, and Southern Brazil

    PubMed Central

    Moreli, Marcos L.; de Sousa, Ricardo L.M.; Borges, Alessandra A.; de Figueiredo, Glauciane G.; Machado, Alex M.; Bisordi, Ivani; Nagasse-Sugahara, Teresa K.; Suzuki, Akemi; Pereira, Luiz E.; de Souza, Renato P.; de Souza, Luiza T.M.; Braconi, Carla T.; Harsi, Charlotte M.; de Andrade Zanotto, Paolo M.

    2009-01-01

    Hantavirus pulmonary syndrome (HPS) is an increasing health problem in Brazil because of encroachment of sprawling urban, agricultural, and cattle-raising areas into habitats of subfamily Sigmodontinae rodents, which serve as hantavirus reservoirs. From 1993 through June 2007, a total of 884 cases of HPS were reported in Brazil (case-fatality rate 39%). To better understand this emerging disease, we collected 89 human serum samples and 68 rodent lung samples containing antibodies to hantavirus from a 2,500-km-wide area in Brazil. RNA was isolated from human samples and rodent tissues and subjected to reverse transcription–PCR. Partial sequences of nucleocapsid protein and glycoprotein genes from 22 human and 16 rodent sources indicated only Araraquara virus and Juquitiba virus lineages. The case-fatality rate of HPS was higher in the area with Araraquara virus. This virus, which may be the most virulent hantavirus in Brazil, was associated with areas that have had greater anthropogenic changes. PMID:19331732

  14. Hantavirus pulmonary syndrome, central plateau, southeastern, and southern Brazil.

    PubMed

    Figueiredo, Luiz T M; Moreli, Marcos L; de-Sousa, Ricardo L M; Borges, Alessandra A; de-Figueiredo, Glauciane G; Machado, Alex M; Bisordi, Ivani; Nagasse-Sugahara, Teresa K; Suzuki, Akemi; Pereira, Luiz E; de-Souza, Renato P; de-Souza, Luiza T M; Braconi, Carla T; Harsi, Charlotte M; de-Andrade-Zanotto, Paolo M

    2009-04-01

    Hantavirus pulmonary syndrome (HPS) is an increasing health problem in Brazil because of encroachment of sprawling urban, agricultural, and cattle-raising areas into habitats of subfamily Sigmodontinae rodents, which serve as hantavirus reservoirs. From 1993 through June 2007, a total of 884 cases of HPS were reported in Brazil (case-fatality rate 39%). To better understand this emerging disease, we collected 89 human serum samples and 68 rodent lung samples containing antibodies to hantavirus from a 2,500-km-wide area in Brazil. RNA was isolated from human samples and rodent tissues and subjected to reverse transcription-PCR. Partial sequences of nucleocapsid protein and glycoprotein genes from 22 human and 16 rodent sources indicated only Araraquara virus and Juquitiba virus lineages. The case-fatality rate of HPS was higher in the area with Araraquara virus. This virus, which may be the most virulent hantavirus in Brazil, was associated with areas that have had greater anthropogenic changes. PMID:19331732

  15. Rodent-borne hantaviruses in Cambodia, Lao PDR, and Thailand.

    PubMed

    Blasdell, Kim; Cosson, Jean François; Chaval, Yannick; Herbreteau, Vincent; Douangboupha, Bounneuang; Jittapalapong, Sathaporn; Lundqvist, Ake; Hugot, Jean-Pierre; Morand, Serge; Buchy, Philippe

    2011-12-01

    In order to evaluate the circulation of hantaviruses present in southeast Asia, a large scale survey of small mammal species was carried out at seven main sites in the region (Cambodia, Lao People's Democratic Republic, and Thailand). Small scale opportunistic trapping was also performed at an eighth site (Cambodia). Using a standard IFA test, IgG antibodies reacting to Hantaan virus antigens were detected at six sites. Antibody prevalence at each site varied from 0 to 5.6% with antibodies detected in several rodent species (Bandicota indica, B. savilei, Maxomys surifer, Mus caroli, M. cookii, Rattus exulans, R. nitidius, R. norvegicus, and R. tanezumi). When site seroprevalence was compared with site species richness, seropositive animals were found more frequently at sites with lower species richness. In order to confirm which hantavirus species were present, a subset of samples was also subjected to RT-PCR. Hantaviral RNA was detected at a single site from each country. Sequencing confirmed the presence of two hantavirus species, Thailand and Seoul viruses, including one sample (from Lao PDR) representing a highly divergent strain of Seoul virus. This is the first molecular evidence of hantavirus in Lao PDR and the first reported L segment sequence data for Thailand virus. PMID:22124701

  16. Structure of the Hantavirus Nucleoprotein Provides Insights into the Mechanism of RNA Encapsidation.

    PubMed

    Olal, Daniel; Daumke, Oliver

    2016-03-01

    Hantaviruses are etiological agents of life-threatening hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. The nucleoprotein (N) of hantavirus is essential for viral transcription and replication, thus representing an attractive target for therapeutic intervention. We have determined the crystal structure of hantavirus N to 3.2 Å resolution. The structure reveals a two-lobed, mostly α-helical structure that is distantly related to that of orthobunyavirus Ns. A basic RNA binding pocket is located at the intersection between the two lobes. We provide evidence that oligomerization is mediated by amino- and C-terminal arms that bind to the adjacent monomers. Based on these findings, we suggest a model for the oligomeric ribonucleoprotein (RNP) complex. Our structure provides mechanistic insights into RNA encapsidation in the genus Hantavirus and constitutes a template for drug discovery efforts aimed at combating hantavirus infections. PMID:26923588

  17. Immunoglobulin A responses to Puumala hantavirus.

    PubMed

    de Carvalho Nicacio, C; Björling, E; Lundkvist, A

    2000-06-01

    Puumala hantavirus (PUUV) causes nephropathia epidemica (NE), a form of haemorrhagic fever with renal syndrome that occurs in northern and central Europe. The immunoglobulin A (IgA) response in NE patients was studied. The levels of total serum IgA in acute-phase samples from NE patients were found to be significantly elevated when compared with the levels in healthy controls. ELISAs for detection of the IgA1 and IgA2 responses against each PUUV structural protein (N, G1 and G2) were developed and evaluated. Sequential sera from NE patients (acute, convalescent, 2-year) and 10-20 year NE-convalescent sera were examined. Most patients developed detectable levels of IgA1 against N and G2, while the G1 responses were low or undetectable. Seven of nine 10-20 year sera contained virus-specific IgA1, which may indicate the prolonged presence of viral antigens after the initial infection. PEPSCAN analysis revealed several IgA-reactive antigenic regions in the N protein. Serum IgA and IgG was purified by affinity chromatography and examined by a virus-neutralization assay. Three of five sera from acute-phase NE patients contained neutralizing IgA1. The diagnostic potential of the PUUV-specific IgA1 response was evaluated. The N and G2 assays showed specificities of 100% with sensitivities of 91 and 84%, respectively, compared with an IgM mu-capture ELISA. Several NE patients, clinically diagnosed for acute PUUV infection, with borderline or undetectable levels of PUUV-specific IgM, were found to be highly positive for the presence of PUUV N-specific serum IgA1, proving the diagnostic value of IgA analysis as a complement to detection of IgM. PMID:10811929

  18. Characterization of human antibody responses to four corners hantavirus infections among patients with hantavirus pulmonary syndrome.

    PubMed Central

    Jenison, S; Yamada, T; Morris, C; Anderson, B; Torrez-Martinez, N; Keller, N; Hjelle, B

    1994-01-01

    Hantavirus pulmonary syndrome (HPS) is a human disease caused by a newly identified hantavirus, which we will refer to as Four Corners virus (FCV). FCV is related most closely to Puumala virus (PUU) and to Prospect Hill virus (PHV). Twenty-five acute HPS serum samples were tested for immunoglobulin G (IgG) and IgM antibody reactivities to FCV-encoded recombinant proteins in Western blot (immunoblot) assays. All HPS serum samples contained both IgG and IgM antibodies to the FCV nucleocapsid (N) protein. FCV N antibodies cross-reacted with PUU N and PHV N proteins. A dominant FCV N epitope was mapped to the segment between amino acids 17 and 59 (QLVTARQKLKDAERAVELDPDDVNKSTLQSRRAAVSALETKLG). All HPS serum samples contained IgG antibodies to the FCV glycoprotein-1 (G1) protein, and 21 of 25 serum samples contained FCV G1 IgM antibodies. The FCV G1 antibodies did not cross-react with PUU G1 and PHV G1 proteins. The FCV G1 type-specific antibody reactivity mapped to a segment between amino acids 59 and 89 (LKIESSCNFDLHVPATTTQKYNQVDWTKKSS). One hundred twenty-eight control serum samples were tested for IgG reactivities to the FCV N and G1 proteins. Nine (7.0%) contained FCV N reactivities, 3 (2.3%) contained FCV G1 reactivities, and one (0.8%) contained both FCV N and FCV G1 reactivities. The epitopes recognized by antibodies present in control serum samples were different from the epitopes recognized by HPS antibodies, suggesting that the control antibody reactivities were unrelated to FCV infections. These reagents constitute a type-specific assay for FCV antibodies. Images PMID:7512156

  19. Cytokine expression during early and late phase of acute Puumala hantavirus infection

    PubMed Central

    2011-01-01

    Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection

  20. An unusual hantavirus outbreak in southern Argentina: person-to-person transmission? Hantavirus Pulmonary Syndrome Study Group for Patagonia.

    PubMed Central

    Wells, R. M.; Sosa Estani, S.; Yadon, Z. E.; Enria, D.; Padula, P.; Pini, N.; Mills, J. N.; Peters, C. J.; Segura, E. L.

    1997-01-01

    Hantavirus pulmonary syndrome is a rodent-borne zoonosis first recognized in the United States in 1993. Person-to-person transmission has not been reported; however, in the outbreak of 20 cases reported here, epidemiologic evidence strongly suggests this route of transmission. PMID:9204298

  1. What Do We Know about How Hantaviruses Interact with Their Different Hosts?

    PubMed Central

    Ermonval, Myriam; Baychelier, Florence; Tordo, Noël

    2016-01-01

    Hantaviruses, like other members of the Bunyaviridae family, are emerging viruses that are able to cause hemorrhagic fevers. Occasional transmission to humans is due to inhalation of contaminated aerosolized excreta from infected rodents. Hantaviruses are asymptomatic in their rodent or insectivore natural hosts with which they have co-evolved for millions of years. In contrast, hantaviruses cause different pathologies in humans with varying mortality rates, depending on the hantavirus species and its geographic origin. Cases of hemorrhagic fever with renal syndrome (HFRS) have been reported in Europe and Asia, while hantavirus cardiopulmonary syndromes (HCPS) are observed in the Americas. In some cases, diseases caused by Old World hantaviruses exhibit HCPS-like symptoms. Although the etiologic agents of HFRS were identified in the early 1980s, the way hantaviruses interact with their different hosts still remains elusive. What are the entry receptors? How do hantaviruses propagate in the organism and how do they cope with the immune system? This review summarizes recent data documenting interactions established by pathogenic and nonpathogenic hantaviruses with their natural or human hosts that could highlight their different outcomes. PMID:27529272

  2. Phylogeny and Origins of Hantaviruses Harbored by Bats, Insectivores, and Rodents

    PubMed Central

    Zhou, Run-Hong; Wang, Jian-Bo; Li, Ming-Hui; Xu, Jianguo; Holmes, Edward C.; Zhang, Yong-Zhen

    2013-01-01

    Hantaviruses are among the most important zoonotic pathogens of humans and the subject of heightened global attention. Despite the importance of hantaviruses for public health, there is no consensus on their evolutionary history and especially the frequency of virus-host co-divergence versus cross-species virus transmission. Documenting the extent of hantavirus biodiversity, and particularly their range of mammalian hosts, is critical to resolving this issue. Here, we describe four novel hantaviruses (Huangpi virus, Lianghe virus, Longquan virus, and Yakeshi virus) sampled from bats and shrews in China, and which are distinct from other known hantaviruses. Huangpi virus was found in Pipistrellus abramus, Lianghe virus in Anourosorex squamipes, Longquan virus in Rhinolophus affinis, Rhinolophus sinicus, and Rhinolophus monoceros, and Yakeshi virus in Sorex isodon, respectively. A phylogenetic analysis of the available diversity of hantaviruses reveals the existence of four phylogroups that infect a range of mammalian hosts, as well as the occurrence of ancient reassortment events between the phylogroups. Notably, the phylogenetic histories of the viruses are not always congruent with those of their hosts, suggesting that cross-species transmission has played a major role during hantavirus evolution and at all taxonomic levels, although we also noted some evidence for virus-host co-divergence. Our phylogenetic analysis also suggests that hantaviruses might have first appeared in Chiroptera (bats) or Soricomorpha (moles and shrews), before emerging in rodent species. Overall, these data indicate that bats are likely to be important natural reservoir hosts of hantaviruses. PMID:23408889

  3. Haploid Genetic Screen Reveals a Profound and Direct Dependence on Cholesterol for Hantavirus Membrane Fusion

    PubMed Central

    Kleinfelter, Lara M.; Jangra, Rohit K.; Jae, Lucas T.; Herbert, Andrew S.; Mittler, Eva; Stiles, Katie M.; Wirchnianski, Ariel S.; Kielian, Margaret; Brummelkamp, Thijn R.

    2015-01-01

    ABSTRACT Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and a highly fatal hantavirus cardiopulmonary syndrome (HCPS) in the New World. No vaccines or antiviral therapies are currently available to prevent or treat hantavirus disease, and gaps in our understanding of how hantaviruses enter cells challenge the search for therapeutics. We performed a haploid genetic screen in human cells to identify host factors required for entry by Andes virus, a highly virulent New World hantavirus. We found that multiple genes involved in cholesterol sensing, regulation, and biosynthesis, including key components of the sterol response element-binding protein (SREBP) pathway, are critical for Andes virus entry. Genetic or pharmacological disruption of the membrane-bound transcription factor peptidase/site-1 protease (MBTPS1/S1P), an SREBP control element, dramatically reduced infection by virulent hantaviruses of both the Old World and New World clades but not by rhabdoviruses or alphaviruses, indicating that this pathway is broadly, but selectively, required by hantaviruses. These results could be fully explained as arising from the modest depletion of cellular membrane cholesterol that accompanied S1P disruption. Mechanistic studies of cells and with protein-free liposomes suggested that high levels of cholesterol are specifically needed for hantavirus membrane fusion. Taken together, our results indicate that the profound dependence on target membrane cholesterol is a fundamental, and unusual, biophysical property of hantavirus glycoprotein-membrane interactions during entry. PMID:26126854

  4. Novel Camelid Antibody Fragments Targeting Recombinant Nucleoprotein of Araucaria hantavirus: A Prototype for an Early Diagnosis of Hantavirus Pulmonary Syndrome

    PubMed Central

    Pereira, Soraya S.; Moreira-Dill, Leandro S.; Morais, Michelle S. S.; Prado, Nidiane D. R.; Barros, Marcos L.; Koishi, Andrea C.; Mazarrotto, Giovanny A. C. A.; Gonçalves, Giselle M.; Zuliani, Juliana P.; Calderon, Leonardo A.; Soares, Andreimar M.; Pereira da Silva, Luiz H.; Duarte dos Santos, Claudia N.; Fernandes, Carla F. C.; Stabeli, Rodrigo G.

    2014-01-01

    In addition to conventional antibodies, camelids produce immunoglobulins G composed exclusively of heavy chains in which the antigen binding site is formed only by single domains called VHH. Their particular characteristics make VHHs interesting tools for drug-delivery, passive immunotherapy and high-throughput diagnosis. Hantaviruses are rodent-borne viruses of the Bunyaviridae family. Two clinical forms of the infection are known. Hemorrhagic Fever with Renal Syndrome (HFRS) is present in the Old World, while Hantavirus Pulmonary Syndrome (HPS) is found on the American continent. There is no specific treatment for HPS and its diagnosis is carried out by molecular or serological techniques, using mainly monoclonal antibodies or hantavirus nucleoprotein (N) to detect IgM and IgG in patient serum. This study proposes the use of camelid VHHs to develop alternative methods for diagnosing and confirming HPS. Phage display technology was employed to obtain VHHs. After immunizing one Lama glama against the recombinant N protein (prNΔ85) of a Brazilian hantavirus strain, VHH regions were isolated to construct an immune library. VHHs were displayed fused to the M13KO7 phage coat protein III and the selection steps were performed on immobilized prNΔ85. After selection, eighty clones recognized specifically the N protein. These were sequenced, grouped based mainly on the CDRs, and five clones were analyzed by western blot (WB), surface plasmon resonance (SPR) device, and ELISA. Besides the ability to recognize prNΔ85 by WB, all selected clones showed affinity constants in the nanomolar range. Additionaly, the clone KC329705 is able to detect prNΔ85 in solution, as well as the native viral antigen. Findings support the hypothesis that selected VHHs could be a powerful tool in the development of rapid and accurate HPS diagnostic assays, which are essential to provide supportive care to patients and reduce the high mortality rate associated with hantavirus infections. PMID

  5. [Hantavirus infection: two case reports from a province in the Eastern Black Sea Region, Turkey].

    PubMed

    Kaya, Selçuk; Yılmaz, Gürdal; Erensoy, Sükrü; Yağçı Çağlayık, Dilek; Uyar, Yavuz; Köksal, Iftihar

    2010-07-01

    Hantaviruses which are the members of Bunyaviridae, differ from other members of this family since they are transmitted to humans by rodents. More than 200.000 cases of hantavirus infections are reported annually worldwide. Hantaviruses can lead to two different types of infection in humans, namely, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is the most common type of hantavirus infection in Europe and Asia and the most common virus types are Dobrava, Puumala, Hantaan and Seoul. A total of 25 hantavirus suspected cases have been reported from the Western Black Sea region of Turkey and 12 of these were confirmed serologically as "Puumala" subtype. Serological tests such as indirect immunofluorescence assay (IFA), are used for diagnosis and typing of the hantaviruses, however, since cross-reactions are common between the subtypes, the results of these tests should be confirmed by other methods. In this report two cases with hantavirus infection defined serologically were presented. Two male patients, 55 and 50 years old, respectively, living in Giresun province of Eastern Black Sea region, Turkey, were admitted to the State Hospital with the complaints of fever, sweating and diarrhoea without blood or mucus. Since thrombocytopenia and renal failure were detected in these two cases, they were transferred to the University Hospital. Presence of fever, thrombocytopenia and renal failure, with no laboratory findings of a bacterial infection and no growth of microoorganisms in the clinical specimens, admittance of the patients during summer and history of being present in the fields, necessitated to rule out leptospirosis, Crimean Kongo hemorrhagic fever and hantavirus infection which were all endemic in our area. Further investigation of the serum samples at the National Reference Virology Laboratory by IFA (Hantavirus Mosaic-1, Euroimmun, Germany) revealed hantavirus IgM and IgG antibodies ≥ 1:100 titer and the results

  6. A Global Perspective on Hantavirus Ecology, Epidemiology, and Disease

    PubMed Central

    Jonsson, Colleen B.; Figueiredo, Luiz Tadeu Moraes; Vapalahti, Olli

    2010-01-01

    Summary: Hantaviruses are enzootic viruses that maintain persistent infections in their rodent hosts without apparent disease symptoms. The spillover of these viruses to humans can lead to one of two serious illnesses, hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. In recent years, there has been an improved understanding of the epidemiology, pathogenesis, and natural history of these viruses following an increase in the number of outbreaks in the Americas. In this review, current concepts regarding the ecology of and disease associated with these serious human pathogens are presented. Priorities for future research suggest an integration of the ecology and evolution of these and other host-virus ecosystems through modeling and hypothesis-driven research with the risk of emergence, host switching/spillover, and disease transmission to humans. PMID:20375360

  7. An outbreak of hantavirus pulmonary syndrome, Chile, 1997.

    PubMed Central

    Toro, J.; Vega, J. D.; Khan, A. S.; Mills, J. N.; Padula, P.; Terry, W.; Yadón, Z.; Valderrama, R.; Ellis, B. A.; Pavletic, C.; Cerda, R.; Zaki, S.; Shieh, W. J.; Meyer, R.; Tapia, M.; Mansilla, C.; Baro, M.; Vergara, J. A.; Concha, M.; Calderon, G.; Enria, D.; Peters, C. J.; Ksiazek, T. G.

    1998-01-01

    An outbreak of 25 cases of Andes virus-associated hantavirus pulmonary syndrome (HPS) was recognized in southern Chile from July 1997 through January 1998. In addition to the HPS patients, three persons with mild hantaviral disease and one person with asymptomatic acute infection were identified. Epidemiologic studies suggested person-to-person transmission in two of three family clusters. Ecologic studies showed very high densities of several species of sigmodontine rodents in the area. PMID:9866751

  8. Antagonism of type I interferon responses by new world hantaviruses.

    PubMed

    Levine, Jessica R; Prescott, Joseph; Brown, Kyle S; Best, Sonja M; Ebihara, Hideki; Feldmann, Heinz

    2010-11-01

    Evasion of interferon (IFN)-mediated antiviral signaling is a common defense strategy for pathogenic RNA viruses. To date, research on IFN antagonism by hantaviruses is limited and has focused on only a subset of the numerous recognized hantavirus species. The host IFN response has two phases, an initiation phase, resulting in the induction of alpha/beta IFN (IFN-α/β), and an amplification phase, whereby IFN-α/β signals through the Jak/STAT pathway, resulting in the establishment of the cellular antiviral state. We examined interactions between these critical host responses and the New World hantaviruses. We observed delayed cellular responses in both Andes virus (ANDV)- and Sin Nombre virus (SNV)-infected A549 and Huh7-TLR3 cells. We found that IFN-β induction is inhibited by coexpression of ANDV nucleocapsid protein (NP) and glycoprotein precursor (GPC) and is robustly inhibited by SNV GPC alone. Downstream amplification by Jak/STAT signaling is also inhibited by SNV GPC and by either NP or GPC of ANDV. Therefore, ANDV- and SNV-encoded proteins have the potential for inhibiting both IFN-β induction and signaling, with SNV exhibiting the more potent antagonism ability. Herein we identify ANDV NP, a previously unrecognized inhibitor of Jak/STAT signaling, and show that IFN antagonism by ANDV relies on expression of both the glycoproteins and NP, whereas the glycoproteins appear to be sufficient for antagonism by SNV. These data suggest that IFN antagonism strategies by hantaviruses are quite variable, even between species with similar disease phenotypes, and may help to better elucidate species-specific pathogenesis. PMID:20844031

  9. Hantavirus pulmonary syndrome: Report of four Alberta cases

    PubMed Central

    Singh, Ameeta E; Werker, Denise H; Boychuk, Lesia R; Miedzinski, Lilly J

    1995-01-01

    Four Alberta cases of hantavirus pulmonary syndrome are reported. Three cases required intensive care, with one experiencing a fulminant course resulting in death. A fourth case with milder illness was identified after epidemiological investigations. Ribavirin was used in one patient who experienced a successful outcome. A recent open label trial has not supported the efficacy of this drug. The epidemiology of Peromyscus maniculatus, the primary rodent host, and the clinical features of this syndrome are summarized. PMID:22514394

  10. Hantavirus Reservoirs: Current Status with an Emphasis on Data from Brazil

    PubMed Central

    Carvalho de Oliveira, Renata; Guterres, Alexandro; Fernandes, Jorlan; D’Andrea, Paulo Sérgio; Bonvicino, Cibele Rodrigues; de Lemos, Elba Regina Sampaio

    2014-01-01

    Since the recognition of hantavirus as the agent responsible for haemorrhagic fever in Eurasia in the 1970s and, 20 years later, the descovery of hantavirus pulmonary syndrome in the Americas, the genus Hantavirus has been continually described throughout the World in a variety of wild animals. The diversity of wild animals infected with hantaviruses has only recently come into focus as a result of expanded wildlife studies. The known reservoirs are more than 80, belonging to 51 species of rodents, 7 bats (order Chiroptera) and 20 shrews and moles (order Soricomorpha). More than 80genetically related viruses have been classified within Hantavirus genus; 25 recognized as human pathogens responsible for a large spectrum of diseases in the Old and New World. In Brazil, where the diversity of mammals and especially rodents is considered one of the largest in the world, 9 hantavirus genotypes have been identified in 12 rodent species belonging to the genus Akodon, Calomys, Holochilus, Oligoryzomys, Oxymycterus, Necromys and Rattus. Considering the increasing number of animals that have been implicated as reservoirs of different hantaviruses, the understanding of this diversity is important for evaluating the risk of distinct hantavirus species as human pathogens. PMID:24784571

  11. Hantavirus pulmonary syndrome and rodent reservoirs in the savanna-like biome of Brazil's southeastern region.

    PubMed

    Limongi, J E; Oliveira, R C; Guterres, A; Costa Neto, S F; Fernandes, J; Vicente, L H B; Coelho, M G; Ramos, V N; Ferreira, M S; Bonvicino, C R; D'Andrea, P S; Lemos, E R S

    2016-04-01

    This paper describes the diversity of rodent fauna in an area endemic for hantavirus cardiopulmonary syndrome (HCPS) in Brazil, the population dynamics and the relationship of rodents with hantavirus in the Cerrado (savanna-like) biome. Additionally, an analysis is made of the partial S segment sequences of the hantaviruses obtained from serologically confirmed human HCPS cases and from rodent specimens. Rodents were collected during four campaigns. Human serum samples were collected from suspected cases of HCPS at hospitals in the state of Minas Gerais. The samples antibody-reactive by ELISA were processed by RT-PCR. The PCR product was amplified and sequenced. Hantavirus was detected only in Necromys lasiurus, the wild rodent species most prevalent in the Cerrado biome (min-max: 50-83·7%). All the six human serum samples were hantavirus seropositive and five showed amplified PCR products. The analysis of the nucleotide sequences showed the circulation of a single genotype, the Araraquara hantavirus. The environmental changes that have occurred in the Cerrado biome in recent decades have favoured N. lasiurus in interspecific competition of habitats, thus increasing the risk of contact between humans and rodent species infected with hantavirus. Our data corroborate the definition of N. lasiurus as the main hantavirus reservoir in the Cerrado biome. PMID:26541807

  12. Whole-Genome Sequence of a Novel Hantavirus Isolated from the European Mole (Talpa europaea).

    PubMed

    Gu, Se Hun; Hejduk, Janusz; Markowski, Janusz; Markowski, Marcin; Liberski, Paweł P; Yanagihara, Richard

    2015-01-01

    The complete genome sequence of Nova virus, a novel hantavirus isolated from a European mole (Talpa europaea) captured in central Poland, was determined. The availability of this sequence will facilitate the search for other mole-borne hantaviruses and will accelerate the acquisition of new knowledge about their phylogeography and evolutionary origin. PMID:26021917

  13. Hantavirus-infection Confers Resistance to Cytotoxic Lymphocyte-Mediated Apoptosis

    PubMed Central

    Gupta, Shawon; Braun, Monika; Tischler, Nicole D.; Stoltz, Malin; Sundström, Karin B.; Björkström, Niklas K.; Ljunggren, Hans-Gustaf; Klingström, Jonas

    2013-01-01

    Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardio-pulmonary syndrome (HCPS; also called hantavirus pulmonary syndrome (HPS)), both human diseases with high case-fatality rates. Endothelial cells are the main targets for hantaviruses. An intriguing observation in patients with HFRS and HCPS is that on one hand the virus infection leads to strong activation of CD8 T cells and NK cells, on the other hand no obvious destruction of infected endothelial cells is observed. Here, we provide an explanation for this dichotomy by showing that hantavirus-infected endothelial cells are protected from cytotoxic lymphocyte-mediated induction of apoptosis. When dissecting potential mechanisms behind this phenomenon, we discovered that the hantavirus nucleocapsid protein inhibits the enzymatic activity of both granzyme B and caspase 3. This provides a tentative explanation for the hantavirus-mediated block of cytotoxic granule-mediated apoptosis-induction, and hence the protection of infected cells from cytotoxic lymphocytes. These findings may explain why infected endothelial cells in hantavirus-infected patients are not destroyed by the strong cytotoxic lymphocyte response. PMID:23555267

  14. Hantavirus testing in small mammal populations of northcentral New Mexico

    SciTech Connect

    Biggs, J.; Bennett, K.; Foxx, T.

    1995-07-01

    In 1993, an outbreak of a new strain of hantavirus in the southwestern US indicated that deer mice (Peromyscus maniculatus) was the primary carrier of the virus. In 1993 and 1994, the Ecological Studies Team (EST) at Los Alamos National Laboratory surveyed small mammal populations in Los Alamos County, New Mexico, primarily for ecological risk assessment (ecorisk) studies. At the request of the Centers for Disease Control (CDC) and the School of Medicine at the University of New Mexico, EST also collected blood samples from captured animals for use in determining seroprevalence of hantavirus in this region due to the recent outbreak of this virus in the four-comers region of the Southwest. The deer mouse was the most commonly captured species during the tripping sessions. Other species sampled included harvest mice (Reithrodontomys megalotis), least chipmunk (Eutamias minimus), long-tailed vole (Microtus longicaudus), Mexican woodrat (Neotoma mexicana), and brush mouse (Peromyscus boylii). The team collected blood samples from tripped animals following CDC`s suggested guidelines. Results of the 1993 and 1994 hantavirus testing identified a total overall seroprevalence of approximately 5.5% and 4.2%, respectively. The highest seroprevalence rates were found in deer mice seri (3--6%), but results on several species were inconclusive; further studies will be necessary, to quantify seroprevalence rates in those species. Seroprevalence rates for Los Alamos County were much lower than elsewhere in the region.

  15. The Role of Mites in the Transmission and Maintenance of Hantaan Virus (Hantavirus: Bunyaviridae)

    PubMed Central

    Yu, Xue-jie; Tesh, Robert B.

    2014-01-01

    This review examines the evidence indicating a role for parasitic mites in the transmission and maintenance of Hantaan virus in nature. The available data, much of it from recent studies in China, indicate that both trombiculid and gamasid mites are naturally infected with Hantaan virus and that infected mites can transmit the virus by bite to laboratory mice and transovarially (vertically) through eggs to their offspring. Collectively, these findings challenge the current paradigm of hantavirus transmission, namely, that rodents serve as the reservoir of human pathogenic hantaviruses in nature and that humans are infected with these viruses by inhalation of aerosols of infectious rodent excreta. Further research is needed to confirm the mite-hantavirus association and to determine if parasitic mites are in fact the major source and principal vectors of human pathogenic hantaviruses, such as Hantaan. If the mite hypothesis is correct, then it will significantly alter current concepts about the epidemiology, prevention, and control of human hantavirus infection. PMID:24958909

  16. Discovery of hantavirus circulating among Rattus rattus in French Mayotte island, Indian Ocean.

    PubMed

    Filippone, Claudia; Castel, Guillaume; Murri, Séverine; Beaulieux, Frédérik; Ermonval, Myriam; Jallet, Corinne; Wise, Emma L; Ellis, Richard J; Marston, Denise A; McElhinney, Lorraine M; Fooks, Anthony R; Desvars, Amélie; Halos, Lénaı G; Vourc'h, Gwenaël; Marianneau, Philippe; Tordo, Noël

    2016-05-01

    Hantaviruses are emerging zoonotic viruses that cause human diseases. In this study, sera from 642 mammals from La Réunion and Mayotte islands (Indian Ocean) were screened for the presence of hantaviruses by molecular analysis. None of the mammals from La Réunion island was positive, but hantavirus genomic RNA was discovered in 29/160 (18 %) Rattus rattus from Mayotte island. The nucleoprotein coding region was sequenced from the liver and spleen of all positive individuals allowing epidemiological and intra-strain variability analyses. Phylogenetic analysis based on complete coding genomic sequences showed that this Murinae-associated hantavirus is a new variant of Thailand virus. Further studies are needed to investigate hantaviruses in rodent hosts and in Haemorrhagic Fever with Renal Syndrome (HFRS) human cases. PMID:26932442

  17. Hantavirus Infection Suppresses Thrombospondin-1 Expression in Cultured Endothelial Cells in a Strain-Specific Manner

    PubMed Central

    Khaiboullina, Svetlana F.; Morzunov, Sergey P.; St. Jeor, Stephen C.; Rizvanov, Albert A.; Lombardi, Vincent C.

    2016-01-01

    Hantavirus infection is associated with two frequently fatal diseases in humans: Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The pathogenesis of hantavirus infection is complex and not fully understood; however, it is believed to involve virus-induced hyperinflammatory immune responses. Thrombospondin-1 (THBS1) is a large homotrimeric protein that plays a putative role in regulating blood homeostasis. Hyperresponsiveness to inflammatory stimuli has also been associated with defects in the THBS1 gene. Our data suggest that hantavirus infection of human umbilical cord vein endothelial cells (HUVEC) suppress the accumulation of THBS1 in the extracellular matrix. Additionally, this suppression is dependent on virus replication, implying a direct mechanism of action. Our data also imply that the pathogenic Andes and Hantaan strains inhibit THBS1 expression while the non-pathogenic Prospect Hill strain showed little inhibition. These observations suggest that a dysregulation of THBS1 may contribute to the pathogenesis of hantavirus infection. PMID:27486439

  18. Hantavirus Infection Suppresses Thrombospondin-1 Expression in Cultured Endothelial Cells in a Strain-Specific Manner.

    PubMed

    Khaiboullina, Svetlana F; Morzunov, Sergey P; St Jeor, Stephen C; Rizvanov, Albert A; Lombardi, Vincent C

    2016-01-01

    Hantavirus infection is associated with two frequently fatal diseases in humans: Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The pathogenesis of hantavirus infection is complex and not fully understood; however, it is believed to involve virus-induced hyperinflammatory immune responses. Thrombospondin-1 (THBS1) is a large homotrimeric protein that plays a putative role in regulating blood homeostasis. Hyperresponsiveness to inflammatory stimuli has also been associated with defects in the THBS1 gene. Our data suggest that hantavirus infection of human umbilical cord vein endothelial cells (HUVEC) suppress the accumulation of THBS1 in the extracellular matrix. Additionally, this suppression is dependent on virus replication, implying a direct mechanism of action. Our data also imply that the pathogenic Andes and Hantaan strains inhibit THBS1 expression while the non-pathogenic Prospect Hill strain showed little inhibition. These observations suggest that a dysregulation of THBS1 may contribute to the pathogenesis of hantavirus infection. PMID:27486439

  19. Puumala hantavirus outbreak among U.S. military health care beneficiaries, Stuttgart, Germany--2012.

    PubMed

    McCormic, Zachary D; Balihe, Michele N; Havas, Karyn A; Baty, Steven A

    2013-12-01

    Hantaviruses are viruses of the family Bunyaviridae that are transmitted to humans via inhalation of the aerosolized excrement of rodents. The geographic distribution of hantavirus includes the Americas, Asia, and Europe. An outbreak of Puumala hantavirus infections among U.S. military health care beneficiaries was identified by the U.S. Army Public Health Command Region-Europe at U.S. Army installations in Stuttgart, Germany, during 2012. Overall, five cases (one probable and four confirmed) were identified in three service members, one U.S. civilian employee, and one dependent family member. Four cases were hospitalized, one of whom required dialysis. The outbreak investigation revealed that all cases exercised in forested areas and most were active smokers (4 out of 5). This report reviews the types of hantaviruses found worldwide and suggests that health care providers should suspect and consider possible hantavirus infections when evaluating patients with histories and clinical presentations consistent with such infections. PMID:24428538

  20. Surveillance of anti-hantavirus antibodies among certain high-risk groups in Taiwan.

    PubMed

    Chen, H L; Yang, J Y; Chen, H Y; Lin, T H; Wang, G R; Horng, C B

    1998-01-01

    Hemorrhagic fever with renal syndrome is a serious health concern in neighboring countries of Taiwan, such as mainland China and Korea. In Taiwan, only two suspected cases were recorded before 1994. The first confirmed case was reported in 1995, but this proved to be imported. To study hantavirus infection in Taiwan, we tested blood collected from garbage collectors, animal handlers, patients with febrile illness of unknown origin, and field rats, the host of hantavirus, for the presence of antibody against hantavirus using an indirect immunofluorescent antibody technique. The positive rates were 1.55% (3/193), 3.45% (1/29), 1.42% (3/211), and 5.56% (9/162), respectively. The subtypes of hantavirus involved were either Hantaan-like or Seoul-like. These results showed that hantavirus may have already invaded Taiwan without our knowledge and physicians should be aware of this. PMID:9481070

  1. Divergent lineage of a novel hantavirus in the banana pipistrelle (Neoromicia nanus) in Côte d'Ivoire

    PubMed Central

    2012-01-01

    Recently identified hantaviruses harbored by shrews and moles (order Soricomorpha) suggest that other mammals having shared ancestry may serve as reservoirs. To investigate this possibility, archival tissues from 213 insectivorous bats (order Chiroptera) were analyzed for hantavirus RNA by RT-PCR. Following numerous failed attempts, hantavirus RNA was detected in ethanol-fixed liver tissue from two banana pipistrelles (Neoromicia nanus), captured near Mouyassué village in Côte d'Ivoire, West Africa, in June 2011. Phylogenetic analysis of partial L-segment sequences using maximum-likelihood and Bayesian methods revealed that the newfound hantavirus, designated Mouyassué virus (MOUV), was highly divergent and basal to all other rodent- and soricomorph-borne hantaviruses, except for Nova virus in the European common mole (Talpa europaea). Full genome sequencing of MOUV and further surveys of other bat species for hantaviruses, now underway, will provide critical insights into the evolution and diversification of hantaviruses. PMID:22281072

  2. Hantavirus infection among children hospitalized for febrile illness suspected to be dengue in Barbados.

    PubMed

    Kumar, Alok; Krishnamurthy, Kandamaran; Nielsen, Anders L

    2016-01-01

    Emerging picture of hantavirus infection in the South America is characterized by greater proportion of childhood infection and wider spectrum of disease from mild asymptomatic to lethal cardiopulmonary disease. Barbados is endemic for dengue and leptospirosis, both of which share clinical features with hantavirus infection and in many cases neither of these diagnosis could be confirmed. We investigate whether some of the children hospitalized with suspected dengue could indeed have been hantavirus infections. In this prospective study children hospitalized with suspected dengue were tested for hantavirus infection using ELISA for the IgM antibodies. Thirty-eight children tested positive for hantavirus infection. They presented with fever, headache and mild respiratory and gastrointestinal symptoms and signs. None of them had features suggestive of hantavirus cardiopulmonary syndrome. Blood count values ranged from low to normal to high for their age. There were no deaths. Hantavirus infection is prevalent in this Caribbean country. It predominantly presents with milder disease and is responsible for some of the nonspecific febrile illnesses in children. PMID:26153080

  3. [Hantavirus pulmonary syndrome in Buenos Aires, 2009-2014].

    PubMed

    Iglesias, Ayelén A; Bellomo, Carla M; Martínez, Valeria P

    2016-01-01

    Andes virus is the causative agent of hantavirus pulmonary syndrome (HPS) in Argentina and neighboring countries. In our country four different areas are affected: Northwest, Southwest, Central and Northeast, where distinct Andes virus genotypes were characterized. Three genotypes were described in Buenos Aires province (Central area): AND-Buenos Aires, AND-Lechiguanas and AND-Plata. In this work, we considered all HPS cases confirmed by ELISA and real time RT-PCR during the period 2009-2014 in Buenos Aires province. The annual distribution, fatality rate and geographic distribution were analyzed. We also analyzed the genotypes involved by RT-PCR and nucleotide sequencing. Finally we evaluated epidemiological data in order to establish the route of transmission. We analyzed 1386 suspect cases of hantavirus infection from Buenos Aires province and we confirmed 88 cases of Hantavirus Pulmonary Syndrome during 2009-2014. The overall average was 14.3 cases per year. The occurrence of a HPS outbreak was confirmed in Buenos Aires province during 2013, showing a 3 fold increase in case number compared to the annual average between 2009 and 2012, tending to normalize during 2014. The overall lethality was 25.6%, with a maximum value of 45.5% in 2011. Genotype analysis was performed in 30.7% of confirmed cases, AND-BsAs show the highest incidence, it was characterized in 72% of the studied cases. Epidemiological data and results of viral genome comparison strongly suggest person-to-person transmission in the three clusters of two cases described in our study. PMID:26826986

  4. [EXPERIMENTAL RESEARCH OF THE HANTAVIRUS SURVIVAL IN COMPLEXES WITH ENVIRONMENTAL SUBSTRATES].

    PubMed

    Iunikhina, O V; Kompanets, G G

    2016-01-01

    Survival of viruses in the environment is a very important problem in epidemiology, especially for infections with indirect transmission. This work describes the results of the experimental study of adsorption and survival of the hantavirus on different environmental substrates (natural organic and inorganic sorbents). Bovine serum albumin (BSA) solution (5-10%) was effective in the hantavirus elution and phosphate-buffer saline (PBS) pH- 7,2 was optimal for elution of specific RNA. Potential survival of the infectious hantavirus on environmental substrates was observed within up to 14 days at +4°C. PMID:27145598

  5. Short report: prevalence of hantavirus infection in rodents associated with two fatal human infections in California.

    PubMed

    Turell, M J; Korch, G W; Rossi, C A; Sesline, D; Enge, B A; Dondero, D V; Jay, M; Ludwig, G V; Li, D; Schmaljohn, C S

    1995-02-01

    Rodents living near two fatal human cases of hantavirus pulmonary syndrome in California were surveyed for evidence of hantavirus infection. Seventeen (15%) (14 Peromyscus maniculatus and one each of P. truei, Eutamias minimus, and Microtus californicus) of 114 rodents tested had evidence (enzyme-linked immunosorbent assay or polymerase chain reaction) of hantavirus infection. This suggests that Peromyscus mice, and P. maniculatus in particular, may be the reservoir for the virus causing this newly recognized disease in California, as previously reported for New Mexico and Arizona. PMID:7872450

  6. Effects of internal fluctuations on the spreading of Hantavirus.

    PubMed

    Escudero, C; Buceta, J; de la Rubia, F J; Lindenberg, Katja

    2004-12-01

    We study the spread of Hantavirus over a host population of deer mice using a population dynamics model. We show that taking into account the internal fluctuations in the mouse population due to its discrete character strongly alters the behavior of the system. In addition to the familiar transition present in the deterministic model, the inclusion of internal fluctuations leads to the emergence of an additional deterministically hidden transition. We determine parameter values that lead to maximal propagation of the disease and discuss some implications for disease prevention policies. PMID:15697402

  7. Effects of internal fluctuations on the spreading of Hantavirus

    NASA Astrophysics Data System (ADS)

    Escudero, C.; Buceta, J.; de La Rubia, F. J.; Lindenberg, Katja

    2004-12-01

    We study the spread of Hantavirus over a host population of deer mice using a population dynamics model. We show that taking into account the internal fluctuations in the mouse population due to its discrete character strongly alters the behavior of the system. In addition to the familiar transition present in the deterministic model, the inclusion of internal fluctuations leads to the emergence of an additional deterministically hidden transition. We determine parameter values that lead to maximal propagation of the disease and discuss some implications for disease prevention policies.

  8. Development and optimization of a PCR assay for detection of Dobrava and Puumala hantaviruses in Bosnia and Herzegovina.

    PubMed

    Smajlović, Lejla; Davoren, Jon; Heyman, Paul; Cochez, Christel; Haas, Cordula; Maake, Caroline; Hukić, Mirsada

    2012-06-01

    Hantavirus-specific serology tests are the main diagnostic technique for detection of hantavirus infection in Bosnia and Herzegovina. In order to enhance hantavirus infections monitoring a sensitive PCR based assay was developed to detect Dobrava (DOBV) and Puumala (PUUV) hantaviruses. Nested primer sets were designed within three different regions of the viral RNA (S and M segment of DOBV and M segment of PUUV) based on highly similar regions from a number of different European hantavirus strains. Assay conditions were optimized using cell cultures infected with DOBV Slovenia, PUUV Sotkamo and PUUV CG 18-20. This sensitive and specific assay has proven to be useful for detection of both Puumala and Dobrava hantaviruses. PMID:22433513

  9. Twenty-Year Summary of Surveillance for Human Hantavirus Infections, United States

    PubMed Central

    Rollin, Pierre E.

    2013-01-01

    In the past 20 years of surveillance for hantavirus in humans in the United States, 624 cases of hantavirus pulmonary syndrome (HPS) have been reported, 96% of which occurred in states west of the Mississippi River. Most hantavirus infections are caused by Sin Nombre virus, but cases of HPS caused by Bayou, Black Creek Canal, Monongahela, and New York viruses have been reported, and cases of domestically acquired hemorrhagic fever and renal syndrome caused by Seoul virus have also occurred. Rarely, hantavirus infections result in mild illness that does not progress to HPS. Continued testing and surveillance of clinical cases in humans will improve our understanding of the etiologic agents involved and the spectrum of diseases. PMID:24274585

  10. Hantavirus infections among overnight visitors to Yosemite National Park, California, USA, 2012.

    PubMed

    Núñez, Jonathan J; Fritz, Curtis L; Knust, Barbara; Buttke, Danielle; Enge, Barryett; Novak, Mark G; Kramer, Vicki; Osadebe, Lynda; Messenger, Sharon; Albariño, César G; Ströher, Ute; Niemela, Michael; Amman, Brian R; Wong, David; Manning, Craig R; Nichol, Stuart T; Rollin, Pierre E; Xia, Dongxiang; Watt, James P; Vugia, Duc J

    2014-03-01

    In summer 2012, an outbreak of hantavirus infections occurred among overnight visitors to Yosemite National Park in California, USA. An investigation encompassing clinical, epidemiologic, laboratory, and environmental factors identified 10 cases among residents of 3 states. Eight case-patients experienced hantavirus pulmonary syndrome, of whom 5 required intensive care with ventilatory support and 3 died. Staying overnight in a signature tent cabin (9 case-patients) was significantly associated with becoming infected with hantavirus (p<0.001). Rodent nests and tunnels were observed in the foam insulation of the cabin walls. Rodent trapping in the implicated area resulted in high trap success rate (51%), and antibodies reactive to Sin Nombre virus were detected in 10 (14%) of 73 captured deer mice. All signature tent cabins were closed and subsequently dismantled. Continuous public awareness and rodent control and exclusion are key measures in minimizing the risk for hantavirus infection in areas inhabited by deer mice. PMID:24565589

  11. Serological Survey of Hantavirus in Inhabitants from Tropical and Subtropical Areas of Brazil.

    PubMed

    Alves Morais, Felipe; Pereira, Alexandre; Santo Pietro Pereira, Aparecida; Lazaro Moreli, Marcos; Marcelo Aranha Camargo, Luís; Schiavo Nardi, Marcello; Farah Tófoli, Cristina; Araujo, Jansen; Mara Dutra, Lilia; Lopes Ometto, Tatiana; Hurtado, Renata; Carmona de Jesus Maués, Fábio; Zingano Hinke, Tiene; Jaber Mahmud, Sati; Correia Lima, Monica; Tadeu Moraes Figueiredo, Luiz; Luiz Durigon, Edison

    2016-01-01

    Brazil has reported more than 1,600 cases of hantavirus cardiopulmonary syndrome (HPS) since 1993, with a 39% rate of reported fatalities. Using a recombinant nucleocapsid protein of Araraquara virus, we performed ELISA to detect IgG antibodies against hantavirus in human sera. The aim of this study was to analyze hantavirus antibody levels in inhabitants from a tropical area (Amazon region) in Rondônia state and a subtropical (Atlantic Rain Forest) region in São Paulo state, Brazil. A total of 1,310 serum samples were obtained between 2003 and 2008 and tested by IgG-ELISA, and 82 samples (6.2%), of which 62 were from the tropical area (5.8%) and 20 from the subtropical area (8.3%), tested positive. Higher levels of hantavirus antibody were observed in inhabitants of the populous subtropical areas compared with those from the tropical areas in Brazil. PMID:27034670

  12. Clinical survey of hantavirus in southern Brazil and the development of specific molecular diagnosis tools.

    PubMed

    Raboni, Sonia M; Rubio, Gisélia; DE Borba, Luana; Zeferino, Aurélio; Skraba, Irene; Goldenberg, Samuel; Dos Santos, Claudia N Duarte

    2005-06-01

    Hantavirus pulmonary syndrome (HPS) is an emerging disease caused by an increasing number of distinct hantavirus serotypes found worldwide. It is also a very severe immune disease. It progresses quickly and is associated with a high mortality rate. At the prodrome phase, hantavirosis symptoms can resemble those of other infectious diseases such as leptospirosis and influenza. Thus, prognosis could be improved by developing a rapid and sensitive diagnostic test for hantavirus infection, and by improving knowledge about clinical aspects of this disease. This study describes clinical features and laboratory parameters throughout the course of HPS in 98 patients. We report the seasonality and regional distribution of this disease in Paraná State, Brazil during the last seven years. In addition, we evaluated a specific molecular diagnostic test based on a nested reverse transcriptase-polymerase chain reaction for the detection of hantaviruses circulating in Brazil. PMID:15964966

  13. A small-scale survey of hantavirus in mammals from Indiana.

    PubMed

    Dietrich, N; Pruden, S; Ksiazek, T G; Morzunov, S P; Camp, J W

    1997-10-01

    In order to determine if hantaviruses were present in mice and other small mammals in Indiana (USA), small mammals were trapped in Brown, LaPorte, Tippecanoe and Whitley counties. Sixty-seven small mammals were trapped during August and September 1994. Sixty-three Peromyscus leucopus, one Microtus pennsylvanicus, one Zapus hudsonius and two Blarina brevicauda were captured and tested for hantaviruses. Six P. leucopus were found to have antibody to Sin Nombre virus (SN) by IgG ELISA, and a 139 bp fragment of SN-like hantavirus was amplified from five of them. All six of the positive P. leucopus were from LaPorte County. No other small mammals had evidence of infection with SN virus. This study presents the first report of Sin Nombre-like hantavirus in P. leucopus from Indiana. PMID:9391967

  14. Serological Survey of Hantavirus in Inhabitants from Tropical and Subtropical Areas of Brazil

    PubMed Central

    Pereira, Alexandre; Santo Pietro Pereira, Aparecida; Lazaro Moreli, Marcos; Marcelo Aranha Camargo, Luís; Schiavo Nardi, Marcello; Farah Tófoli, Cristina; Araujo, Jansen; Mara Dutra, Lilia; Lopes Ometto, Tatiana; Hurtado, Renata; Carmona de Jesus Maués, Fábio; Zingano Hinke, Tiene; Jaber Mahmud, Sati; Correia Lima, Monica; Tadeu Moraes Figueiredo, Luiz; Luiz Durigon, Edison

    2016-01-01

    Brazil has reported more than 1,600 cases of hantavirus cardiopulmonary syndrome (HPS) since 1993, with a 39% rate of reported fatalities. Using a recombinant nucleocapsid protein of Araraquara virus, we performed ELISA to detect IgG antibodies against hantavirus in human sera. The aim of this study was to analyze hantavirus antibody levels in inhabitants from a tropical area (Amazon region) in Rondônia state and a subtropical (Atlantic Rain Forest) region in São Paulo state, Brazil. A total of 1,310 serum samples were obtained between 2003 and 2008 and tested by IgG-ELISA, and 82 samples (6.2%), of which 62 were from the tropical area (5.8%) and 20 from the subtropical area (8.3%), tested positive. Higher levels of hantavirus antibody were observed in inhabitants of the populous subtropical areas compared with those from the tropical areas in Brazil. PMID:27034670

  15. Hantavirus Infections among Overnight Visitors to Yosemite National Park, California, USA, 2012

    PubMed Central

    Núñez, Jonathan J.; Fritz, Curtis L.; Knust, Barbara; Buttke, Danielle; Enge, Barryett; Novak, Mark G.; Kramer, Vicki; Osadebe, Lynda; Messenger, Sharon; Albariño, César G.; Ströher, Ute; Niemela, Michael; Amman, Brian R.; Wong, David; Manning, Craig R.; Nichol, Stuart T.; Rollin, Pierre E.; Xia, Dongxiang; Watt, James P.

    2014-01-01

    In summer 2012, an outbreak of hantavirus infections occurred among overnight visitors to Yosemite National Park in California, USA. An investigation encompassing clinical, epidemiologic, laboratory, and environmental factors identified 10 cases among residents of 3 states. Eight case-patients experienced hantavirus pulmonary syndrome, of whom 5 required intensive care with ventilatory support and 3 died. Staying overnight in a signature tent cabin (9 case-patients) was significantly associated with becoming infected with hantavirus (p<0.001). Rodent nests and tunnels were observed in the foam insulation of the cabin walls. Rodent trapping in the implicated area resulted in high trap success rate (51%), and antibodies reactive to Sin Nombre virus were detected in 10 (14%) of 73 captured deer mice. All signature tent cabins were closed and subsequently dismantled. Continuous public awareness and rodent control and exclusion are key measures in minimizing the risk for hantavirus infection in areas inhabited by deer mice. PMID:24565589

  16. Twenty-year summary of surveillance for human hantavirus infections, United States.

    PubMed

    Knust, Barbara; Rollin, Pierre E

    2013-12-01

    In the past 20 years of surveillance for hantavirus in humans in the United States, 624 cases of hantavirus pulmonary syndrome (HPS) have been reported, 96% of which occurred in states west of the Mississippi River. Most hantavirus infections are caused by Sin Nombre virus, but cases of HPS caused by Bayou, Black Creek Canal, Monongahela, and New York viruses have been reported, and cases of domestically acquired hemorrhagic fever and renal syndrome caused by Seoul virus have also occurred. Rarely, hantavirus infections result in mild illness that does not progress to HPS. Continued testing and surveillance of clinical cases in humans will improve our understanding of the etiologic agents involved and the spectrum of diseases. PMID:24274585

  17. Hantavirus-induced disruption of the endothelial barrier: neutrophils are on the payroll.

    PubMed

    Schönrich, Günther; Krüger, Detlev H; Raftery, Martin J

    2015-01-01

    Viral hemorrhagic fever caused by hantaviruses is an emerging infectious disease for which suitable treatments are not available. In order to improve this situation a better understanding of hantaviral pathogenesis is urgently required. Hantaviruses infect endothelial cell layers in vitro without causing any cytopathogenic effect and without increasing permeability. This implies that the mechanisms underlying vascular hyperpermeability in hantavirus-associated disease are more complex and that immune mechanisms play an important role. In this review we highlight the latest developments in hantavirus-induced immunopathogenesis. A possible contribution of neutrophils has been neglected so far. For this reason, we place special emphasis on the pathogenic role of neutrophils in disrupting the endothelial barrier. PMID:25859243

  18. Hantavirus pulmonary syndrome in a highly endemic area of Brazil.

    PubMed

    Oliveira, R C; Sant'ana, M M; Guterres, A; Fernandes, J; Hillesheim, N L F K; Lucini, C; Gomes, R; Lamas, C; Bochner, R; Zeccer, S; DE Lemos, E R S

    2016-04-01

    Hantavirus pulmonary syndrome (HPS) is the most frequently reported fatal rodent-borne disease in Brazil, with the majority of cases occurring in Santa Catarina. We analysed the clinical, laboratory and epidemiological data of the 251 confirmed cases of HPS in Santa Catarina in 1999-2011. The number of cases ranged from 10 to 47 per year, with the highest incidences in 2004-2006. Gastrointestinal tract manifestations were found in >60% of the cases, potentially confounding diagnosis and leading to inappropriate therapy. Dyspnoea, acute respiratory failure, renal failure, increased serum creatinine and urea levels, increased haematocrits and the presence of pulmonary interstitial infiltrate were significantly more common in HPS patients who died. In addition, we demonstrated that the six cases from the midwest region of the state were associated with Juquitiba virus genotype. The case-fatality rate in this region, 19·2%, was lower than that recorded for other mesoregions. In the multivariate analysis increase of serum creatinine and urea was associated with death by HPS. Our findings help elucidate the epidemiology of HPS in Brazil, where mast seeding of bamboo can trigger rodent population eruptions and subsequent human HPS outbreaks. We also emphasize the need for molecular confirmation of the hantavirus genotype of human cases for a better understanding of the mortality-related factors associated with HPS cases in Brazil. PMID:26464248

  19. The hantaviruses of Europe: from the bedside to the bench.

    PubMed Central

    Clement, J.; Heyman, P.; McKenna, P.; Colson, P.; Avsic-Zupanc, T.

    1997-01-01

    In Europe, hantavirus disease can hardly be called an emerging zoonosis; it is rather a rediscovered disease. Since 1934 an epidemic condition with primarily renal involvement has been described in Sweden. Nowadays, hundreds to thousands of cases per year are registered in Fennoscandia, fluctuating with the numbers of the specific Arvicoline-rodent reservoir, the red bank vole, which carries the main European serotype, Puumala (PUU). In the early 1980s, the rat-transmitted serotype, Seoul (SEO), caused laboratory outbreaks throughout Europe, and recent reports also suggest sporadic, wild rat-spread hantavirus disease. In the Balkans, at least four serotypes are present simultaneously: PUU, SEO, the "Korean" prototype Hantaan (HTN) or HTN-like types, and Dobrava, the latter causing a mortality rate of up to 20%. Moreover, recent genotyping studies have disclosed several PUU-like genotypes spread in Europe and/or Russia by other genera of the Arvicoline-rodent subfamily: Tula, Tobetsu, Khabarovsk, and Topografov. Their importance for human pathogenicity is still unclear, but serologic cross-reactions with PUU antigen might have caused their misdiagnosis as PUU-infections in the past. PMID:9204306

  20. Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques

    PubMed Central

    Safronetz, David; Prescott, Joseph; Feldmann, Friederike; Haddock, Elaine; Rosenke, Rebecca; Okumura, Atsushi; Brining, Douglas; Dahlstrom, Eric; Porcella, Stephen F.; Ebihara, Hideki; Scott, Dana P.; Hjelle, Brian; Feldmann, Heinz

    2014-01-01

    The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases. PMID:24778254

  1. Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques.

    PubMed

    Safronetz, David; Prescott, Joseph; Feldmann, Friederike; Haddock, Elaine; Rosenke, Rebecca; Okumura, Atsushi; Brining, Douglas; Dahlstrom, Eric; Porcella, Stephen F; Ebihara, Hideki; Scott, Dana P; Hjelle, Brian; Feldmann, Heinz

    2014-05-13

    The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases. PMID:24778254

  2. Old World Hantaviruses in Rodents in New Orleans, Louisiana

    PubMed Central

    Cross, Robert W.; Waffa, Bradley; Freeman, Ashley; Riegel, Claudia; Moses, Lina M.; Bennett, Andrew; Safronetz, David; Fischer, Elizabeth R.; Feldmann, Heinz; Voss, Thomas G.; Bausch, Daniel G.

    2014-01-01

    Seoul virus, an Old World hantavirus, is maintained in brown rats and causes a mild form of hemorrhagic fever with renal syndrome (HFRS) in humans. We captured rodents in New Orleans, Louisiana and tested them for the presence of Old World hantaviruses by reverse transcription polymerase chain reaction (RT-PCR) with sequencing, cell culture, and electron microscopy; 6 (3.4%) of 178 rodents captured—all brown rats—were positive for a Seoul virus variant previously coined Tchoupitoulas virus, which was noted in rodents in New Orleans in the 1980s. The finding of Tchoupitoulas virus in New Orleans over 25 years since its first discovery suggests stable endemicity in the city. Although the degree to which this virus causes human infection and disease remains unknown, repeated demonstration of Seoul virus in rodent populations, recent cases of laboratory-confirmed HFRS in some US cities, and a possible link with hypertensive renal disease warrant additional investigation in both rodents and humans. PMID:24639295

  3. [En route in Switzerland - tick-borne and hantavirus infections].

    PubMed

    Schmid, Sabine; Aliyev, Eldar; Engler, Olivier; Mütsch, Margot

    2013-06-01

    Tick-borne infections are endemic in Switzerland with borreliosis being the most frequent one, followed by the vaccine-preventable tick-borne encephalitis and more rarely by anaplasmosis, rickettsioses and babesiosis. Short characteristics of these infections are presented. The main preventive measures for stays in endemic regions include not leaving forest tracks and wearing closely fitted clothes and shoes, impregnated with an insecticide. Following at-risk activities, clothes as well as the body should be searched for ticks and they have to be removed using a tick removing tool. The body area of the tick bite has to be observed and a physician visit is strongly urged in case of rising fever and/or of erythema migrans. Hantavirus infections: Nephropathia epidemica is a zoonosis caused by the Puumala type of hantavirus and transmission occurs by inhaling aerolized excretions of the bank vole. There is no known human to human transmission. The incidence of this infection varies in a cyclic fashion and typical clinical symptoms include sudden onset of fever, headache, abdominal and back pain and transient renal impairment with initial oliguria and later polyuria. At-risk activities include camping and cleaning of rodent infestations. In these cases, face masks should be worn and the excretions be moistened before cleaning is started. In Germany, 2 - 3 years-cycles of outbreaks were observed between 2005 and 2012 with regional clusters approaching Switzerland. Therefore, disease awareness of physicians and infection surveillance are essential. PMID:23732453

  4. Preferential host switching and its relation with Hantavirus diversification in South America.

    PubMed

    Rivera, Paula C; González-Ittig, Raul E; Gardenal, Cristina N

    2015-09-01

    In recent years, the notion of co-speciation between Hantavirus species and their hosts was discarded in favour of a more likely explanation: preferential host switching. However, the relative importance of this last process in shaping the evolutionary history of hantaviruses remains uncertain, given the present limited knowledge not only of virus-host relationships but also of the pathogen and reservoir phylogenies. In South America, more than 25 hantavirus genotypes were detected; several of them act as aetiological agents of hantavirus pulmonary syndrome (HPS). An understanding of the diversity of hantaviruses and of the processes underlying host switching is critical since human cases of HPS are almost exclusively the result of human-host interactions. In this study, we tested if preferential host switching is the main process driving hantavirus diversification in South America, by performing a co-phylogenetic analysis of the viruses and their primary hosts. We also suggest a new level of amino acid divergence to define virus species in the group. Our results indicate that preferential host switching would not be the main process driving virus diversification. The historical geographical proximity among rodent hosts emerges as an alternative hypothesis to be tested. PMID:26048884

  5. Hantavirus Pulmonary Syndrome , Southern Chile, 1995–2012

    PubMed Central

    Riquelme, Raúl; Rioseco, María Luisa; Bastidas, Lorena; Trincado, Daniela; Riquelme, Mauricio; Loyola, Hugo; Valdivieso, Francisca

    2015-01-01

    Hantavirus is endemic to the Region de Los Lagos in southern Chile; its incidence is 8.5 times higher in the communes of the Andean area than in the rest of the region. We analyzed the epidemiologic aspects of the 103 cases diagnosed by serology and the clinical aspects of 80 hospitalized patients during 1995–2012. Cases in this region clearly predominated during winter, whereas in the rest of the country, they occur mostly during summer. Mild, moderate, and severe disease was observed, and the case-fatality rate was 32%. Shock caused death in 75% of those cases; high respiratory frequency and elevated creatinine plasma level were independent factors associated with death. Early clinical suspicion, especially in rural areas, should prompt urgent transfer to a hospital with an intensive care unit and might help decrease the high case-fatality rate. PMID:25816116

  6. Seroepidemiologic studies of hantavirus infection among wild rodents in California.

    PubMed Central

    Jay, M.; Ascher, M. S.; Chomel, B. B.; Madon, M.; Sesline, D.; Enge, B. A.; Hjelle, B.; Ksiazek, T. G.; Rollin, P. E.; Kass, P. H.; Reilly, K.

    1997-01-01

    A total of 4,626 mammals were serologically tested for antibodies to Sin Nombre virus. All nonrodent species were antibody negative. Among wild rodents, antibody prevalence was 8.5% in murids, 1.4% in heteromyids, and < 0.1% in sciurids. Of 1,921 Peromyscus maniculatus (deer mice), 226 (11.8%) were antibody positive, including one collected in 1975. The highest antibody prevalence (71.4% of 35) was found among P. maniculatus on Santa Cruz Island, off the southern California coast. Prevalence of antibodies among deer mice trapped near sites of human cases (26.8% of 164) was significantly higher than that of mice from other sites (odds ratio = 4.5; 95% confidence interval = 1.7, 11.6). Antibody prevalence increased with rising elevation (> 1,200 meters) and correlated with a spatial cluster of hantavirus pulmonary syndrome cases in the Sierra Nevada. PMID:9204301

  7. In Search for Factors that Drive Hantavirus Epidemics

    PubMed Central

    Heyman, Paul; Thoma, Bryan R.; Marié, Jean-Lou; Cochez, Christel; Essbauer, Sandra Simone

    2012-01-01

    In Europe, hantaviruses (Bunyaviridae) are small mammal-associated zoonotic and emerging pathogens that can cause hemorrhagic fever with renal syndrome (HFRS). Puumala virus, the main etiological agent carried by the bank vole Myodes glareolus is responsible for a mild form of HFRS while Dobrava virus induces less frequent but more severe cases of HFRS. Since 2000 in Europe, more than 3000 cases of HFRS have been recorded, in average, each year, which is nearly double compared to the previous decade. In addition to this upside long-term trend, significant oscillations occur. Epidemic years appear, usually every 2–4 years, with an increased incidence, generally in localized hot spots. Moreover, the virus has been identified in new areas in the recent years. A great number of surveys have been carried out in order to assess the prevalence of the infection in the reservoir host and to identify links with different biotic and abiotic factors. The factors that drive the infections are related to the density and diversity of bank vole populations, prevalence of infection in the reservoir host, viral excretion in the environment, survival of the virus outside its host, and human behavior, which affect the main transmission virus route through inhalation of infected rodent excreta. At the scale of a rodent population, the prevalence of the infection increases with the age of the individuals but also other parameters, such as sex and genetic variability, interfere. The contamination of the environment may be correlated to the number of newly infected rodents, which heavily excrete the virus. The interactions between these different parameters add to the complexity of the situation and explain the absence of reliable tools to predict epidemics. In this review, the factors that drive the epidemics of hantaviruses in Middle Europe are discussed through a panorama of the epidemiological situation in Belgium, France, and Germany. PMID:22934002

  8. Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc

    PubMed Central

    Barriga, Gonzalo P.; Villalón-Letelier, Fernando; Márquez, Chantal L.; Bignon, Eduardo A.; Acuña, Rodrigo; Ross, Breyan H.; Monasterio, Octavio; Mardones, Gonzalo A.; Vidal, Simon E.; Tischler, Nicole D.

    2016-01-01

    Hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. Previously, we have shown that the Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins. The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region. Such fragments are thought to interact with the core of the fusion protein trimer during the transition from its pre-fusion to its post-fusion conformation. Based on our previous homology model structure for Gc from Andes hantavirus (ANDV), here we predicted and generated recombinant DIII and stem peptides to test whether these fragments inhibit hantavirus membrane fusion and cell entry. Recombinant ANDV DIII was soluble, presented disulfide bridges and beta-sheet secondary structure, supporting the in silico model. Using DIII and the C-terminal part of the stem region, the infection of cells by ANDV was blocked up to 60% when fusion of ANDV occurred within the endosomal route, and up to 95% when fusion occurred with the plasma membrane. Furthermore, the fragments impaired ANDV glycoprotein-mediated cell-cell fusion, and cross-inhibited the fusion mediated by the glycoproteins from Puumala virus (PUUV). The Gc fragments interfered in ANDV cell entry by preventing membrane hemifusion and pore formation, retaining Gc in a non-resistant homotrimer stage, as described for DIII and stem peptide inhibitors of class II fusion proteins. Collectively, our results demonstrate that hantavirus Gc shares not only structural, but also mechanistic similarity with class II viral fusion proteins, and will hopefully help in developing novel therapeutic strategies against hantaviruses

  9. Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc.

    PubMed

    Barriga, Gonzalo P; Villalón-Letelier, Fernando; Márquez, Chantal L; Bignon, Eduardo A; Acuña, Rodrigo; Ross, Breyan H; Monasterio, Octavio; Mardones, Gonzalo A; Vidal, Simon E; Tischler, Nicole D

    2016-07-01

    Hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. Previously, we have shown that the Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins. The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region. Such fragments are thought to interact with the core of the fusion protein trimer during the transition from its pre-fusion to its post-fusion conformation. Based on our previous homology model structure for Gc from Andes hantavirus (ANDV), here we predicted and generated recombinant DIII and stem peptides to test whether these fragments inhibit hantavirus membrane fusion and cell entry. Recombinant ANDV DIII was soluble, presented disulfide bridges and beta-sheet secondary structure, supporting the in silico model. Using DIII and the C-terminal part of the stem region, the infection of cells by ANDV was blocked up to 60% when fusion of ANDV occurred within the endosomal route, and up to 95% when fusion occurred with the plasma membrane. Furthermore, the fragments impaired ANDV glycoprotein-mediated cell-cell fusion, and cross-inhibited the fusion mediated by the glycoproteins from Puumala virus (PUUV). The Gc fragments interfered in ANDV cell entry by preventing membrane hemifusion and pore formation, retaining Gc in a non-resistant homotrimer stage, as described for DIII and stem peptide inhibitors of class II fusion proteins. Collectively, our results demonstrate that hantavirus Gc shares not only structural, but also mechanistic similarity with class II viral fusion proteins, and will hopefully help in developing novel therapeutic strategies against hantaviruses

  10. Second external quality assurance study for the serological diagnosis of hantaviruses in Europe.

    PubMed

    Escadafal, Camille; Avšič-Županc, Tatjana; Vapalahti, Olli; Niklasson, Bo; Teichmann, Anette; Niedrig, Matthias; Donoso-Mantke, Oliver

    2012-01-01

    Hantaviruses are endemic throughout the world and hosted by rodents and insectivores. Two human zoonoses, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), are caused by hantaviruses and case fatality rates have reached 12% for HFRS and 50% for HPS in some outbreaks. Symptomatic hantavirus infections in Europe are summarised as HFRS mainly due to Puumala, Dobrava-Belgrade and Saaremaa virus. While HFRS has an overall low incidence in Europe, the number of cases varies from 100 per year in all Eastern and Southern Europe up to 1,000 per year only in Finland. To assess the quality of hantavirus diagnostics, the European Network for the Diagnostics of "Imported" Viral Diseases (ENIVD) organised a first external quality assurance (EQA) in 2002. The purpose of this second EQA study is to collect updated information on the efficiency and accurateness of hantavirus serological methods applied by expert laboratories. A serum panel of 14 samples was sent to 28 participants in Europe of which 27 sent results. Performance in hantavirus diagnosis varied not only on the method used but also on the laboratories and the subclass of antibodies tested. Commercial and in-house assays performed almost equally. Enzyme immunoassays were mainly used but did not show the best performances while immunoblot assays were the less employed and showed overall better performances. IgM antibodies were not detected in 61% of the positive IgM samples and IgM detection was not performed by 7% of the laboratories indicating a risk of overlooking acute infections in patients. Uneven performances using the same method is indicating that there is still a need for improving testing conditions and standardizing protocols. PMID:22509420

  11. Does proficiency testing improve the quality of hantavirus serodiagnostics? Experiences with INSTAND EQA schemes.

    PubMed

    Hofmann, Jörg; Grunert, Hans-Peter; Donoso-Mantke, Oliver; Zeichhardt, Heinz; Kruger, Detlev H

    2015-10-01

    Hantavirus infections in Germany appear periodically with peak numbers every 2-3 years. The reported cases in the years 2007, 2010 and 2012 exceeded many times over those in the years in-between. In order to reveal faults of certain in vitro diagnostic assays (IVDs), to harmonize the performances of the individual assays and to improve the users' competence in interpreting the results, the National Consiliary Laboratory for Hantaviruses and INSTAND e.V. (Society for Promoting Quality Assurance in Medical Laboratories e.V.) established an external quality assessment (EQA) scheme for proficiency testing of hantavirus serodiagnostics. The first EQA scheme (pilot study) started in March 2009 with 58 participating laboratories from Germany and neighboring countries. Twice a year four serum samples were sent out to the participants to investigate whether the sample reflects an acute or past infection and to distinguish between infections with the hantavirus types Puumala virus (PUUV) and Dobrava-Belgrade virus (DOBV), both endemic in Central Europe. In addition, samples negative for anti-hantavirus antibodies were tested in order to examine the specificity of the IVDs applied in the participating laboratories. An increasing number of laboratories participated, with a maximum of 92 in March 2014. When summarizing in total 2592 test results, the laboratories reached an overall specificity of 96.7% and a sensitivity of 95% in their detection of a hantavirus infection. A correct distinction between acute and past infections was forwarded in 90-96% of replies of laboratories. Exact serotyping (PUUV vs. DOBV) of the infection was reported in 81-96% of replies with the lowest accuracy for past DOBV infections; cross-reactivities between diagnostic antigens of the two viruses as well as persistent IgM titers in humans may interfere with exact testing. The EQAs revealed acceptable results for the serodiagnostic of hantavirus infection including serotyping but further improvement

  12. Accidentes en plantas nucleares de electricidad y el riesgo de cáncer

    Cancer.gov

    Hoja informativa acerca de los riesgos del cáncer asociados con accidentes en plantas nucleares de electricidad. Incluye información para pacientes con cáncer que viven en una zona que puede haber sido afectada por un accidente en una planta nuclear.

  13. Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein Reveals the Mechanism for Ribonucleoprotein Complex Formation

    PubMed Central

    Guo, Yu; Wang, Wenming; Sun, Yuna; Ma, Chao; Wang, Xu; Wang, Xin; Liu, Pi; Shen, Shu; Li, Baobin; Lin, Jianping; Deng, Fei

    2015-01-01

    ABSTRACT Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae, infect mammals, including humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal structure of the core domains of NP (NPcore) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV), which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV NPcore exclude the N- and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in RNA binding and virus replication. We further demonstrated that the C-terminal helix and the linker region connecting the N-terminal coiled-coil domain and NPcore are essential for hantavirus NP oligomerization through contacts made with two adjacent protomers. Moreover, electron microscopy (EM) visualization of native RNPs extracted from the virions revealed that a monomer-sized NP-RNA complex is the building block of viral RNP. This work provides insight into the formation of hantavirus RNP and provides an understanding of the evolutionary connections that exist among bunyaviruses. IMPORTANCE Hantaviruses are distributed across a wide and increasing range of host reservoirs throughout the world. In particular, hantaviruses can be transmitted via aerosols of rodent excreta to humans or from human to human and cause HFRS and HCPS, with mortalities of 15% and 50%, respectively. Hantavirus is therefore listed as a category C pathogen. Hantavirus encodes an NP that plays essential roles both in RNP formation and

  14. Hantavirus seropositivity in rodents in relation to habitat heterogeneity in human-shaped landscapes of Southeast Asia.

    PubMed

    Blasdell, Kim; Morand, Serge; Henttonen, Heikki; Tran, Annelise; Buchy, Philippe

    2016-05-01

    To establish how the conversion of natural habitats for agricultural purposes may impact the distribution of hantaviruses in Southeast Asia, we tested how habitat structure affects hantavirus infection prevalence of common murine rodents that inhabit human-dominated landscapes in this region. For this, we used geo-referenced data of rodents analysed for hantavirus infection and land cover maps produced for the seven study sites in Thailand, Cambodia and Lao PDR where they were collected. Rodents were tested by serological methods that detect several hantaviruses, including pathogenic ones. Rodents with a seropositive status were more likely to be found near to agriculture on steep land, and also in environments with a high proportion of agriculture on steep land. These results suggest that in Southeast Asia, hantaviruses, which are often associated with generalist rodent species with a preference for agricultural land, may benefit from land conversion to agriculture. PMID:27246270

  15. Development and validation of a point-of-care test for detecting hantavirus antibodies in human and rodent samples.

    PubMed

    Koishi, Andrea Cristine; Aoki, Mateus Nóbrega; Jorge, Taissa Ricciardi; Suzukawa, Andréia Akemi; Zanluca, Camila; Levis, Silvana; Duarte Dos Santos, Claudia Nunes

    2016-07-01

    Hantaviruses are etiologic agents of a zoonotic disease transmitted mainly from wild rodents to humans, causing Hemorrhagic Fever with Renal Syndrome in Eurasia and the Hantavirus Cardiopulmonary Syndrome in the Americas (HCPS), reaching a lethality rate of 40% in Brazil. Hantavirus diagnostic and seroprevalence are often based on the presence of IgM and IgG antibodies against the virus. Here we propose a rapid test assay able to identify hantavirus antibodies with sensibility and specificity similar to ELISA assays. We analyzed five groups of samples, including healthy human population and small mammals of endemic areas, suspected cases of HCPS, patients with non-related infections and a serum panel from a different geographical region. The test presented good rates of sensibility (87-100%) and specificity (97-100%) for all groups, being a promising tool suitable for both rodent and human hantavirus epidemiological surveys. PMID:27155935

  16. Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters

    PubMed Central

    Hammerbeck, Christopher D.; Brocato, Rebecca L.; Bell, Todd M.; Schellhase, Christopher W.; Mraz, Steven R.; Queen, Laurie A.

    2016-01-01

    ABSTRACT Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, dysregulation of components of the immune response is often suggested as a possible cause. Alveolar macrophages are found in the alveoli of the lung and represent the first line of defense to many airborne pathogens. To determine whether alveolar macrophages play a role in HPS pathogenesis, alveolar macrophages were depleted in an adult rodent model of HPS that closely resembles human HPS. Syrian hamsters were treated, intratracheally, with clodronate-encapsulated liposomes or control liposomes and were then challenged with ANDV. Treatment with clodronate-encapsulated liposomes resulted in significant reduction in alveolar macrophages, but depletion did not prevent pathogenesis or prolong disease. Depletion also did not significantly reduce the amount of virus in the lung of ANDV-infected hamsters but altered neutrophil recruitment, MIP-1α and MIP-2 chemokine expression, and vascular endothelial growth factor (VEGF) levels in hamster bronchoalveolar lavage (BAL) fluid early after intranasal challenge. These data demonstrate that alveolar macrophages may play a limited protective role early after exposure to aerosolized ANDV but do not directly contribute to hantavirus disease pathogenesis in the hamster model of HPS. IMPORTANCE Hantaviruses continue to cause disease worldwide for which there are no FDA-licensed vaccines, effective postexposure prophylactics, or therapeutics. Much of this can be attributed to a poor understanding of the mechanism of hantavirus disease pathogenesis. Hantavirus disease has long been considered an immune-mediated disease; however, by directly manipulating the Syrian hamster model, we continue to eliminate individual immune cell types. As the most numerous immune cells present in the respiratory tract

  17. Clinical course and long-term outcome of hantavirus-associated nephropathia epidemica, Germany.

    PubMed

    Latus, Joerg; Schwab, Matthias; Tacconelli, Evelina; Pieper, Friedrich-Michael; Wegener, Daniel; Dippon, Juergen; Müller, Simon; Zakim, David; Segerer, Stephan; Kitterer, Daniel; Priwitzer, Martin; Mezger, Barbara; Walter-Frank, Birgit; Corea, Angela; Wiedenmann, Albrecht; Brockmann, Stefan; Pöhlmann, Christoph; Alscher, M Dominik; Braun, Niko

    2015-01-01

    Human infection with Puumala virus (PUUV), the most common hantavirus in Central Europe, causes nephropathia epidemica (NE), a disease characterized by acute kidney injury and thrombocytopenia. To determine the clinical phenotype of hantavirus-infected patients and their long-term outcome and humoral immunity to PUUV, we conducted a cross-sectional prospective survey of 456 patients in Germany with clinically and serologically confirmed hantavirus-associated NE during 2001-2012. Prominent clinical findings during acute NE were fever and back/limb pain, and 88% of the patients had acute kidney injury. At follow-up (7-35 mo), all patients had detectable hantavirus-specific IgG; 8.5% had persistent IgM; 25% had hematuria; 23% had hypertension (new diagnosis for 67%); and 7% had proteinuria. NE-associated hypertension and proteinuria do not appear to have long-term consequences, but NE-associated hematuria may. All patients in this study had hantavirus-specific IgG up to years after the infection. PMID:25533268

  18. Clinical Course and Long-Term Outcome of Hantavirus-Associated Nephropathia Epidemica, Germany

    PubMed Central

    Latus, Joerg; Schwab, Matthias; Tacconelli, Evelina; Pieper, Friedrich-Michael; Wegener, Daniel; Dippon, Juergen; Müller, Simon; Zakim, David; Segerer, Stephan; Kitterer, Daniel; Priwitzer, Martin; Mezger, Barbara; Walter-Frank, Birgit; Corea, Angela; Wiedenmann, Albrecht; Brockmann, Stefan; Pöhlmann, Christoph; Alscher, M. Dominik

    2015-01-01

    Human infection with Puumala virus (PUUV), the most common hantavirus in Central Europe, causes nephropathia epidemica (NE), a disease characterized by acute kidney injury and thrombocytopenia. To determine the clinical phenotype of hantavirus-infected patients and their long-term outcome and humoral immunity to PUUV, we conducted a cross-sectional prospective survey of 456 patients in Germany with clinically and serologically confirmed hantavirus-associated NE during 2001–2012. Prominent clinical findings during acute NE were fever and back/limb pain, and 88% of the patients had acute kidney injury. At follow-up (7–35 mo), all patients had detectable hantavirus-specific IgG; 8.5% had persistent IgM; 25% had hematuria; 23% had hypertension (new diagnosis for 67%); and 7% had proteinuria. NE-associated hypertension and proteinuria do not appear to have long-term consequences, but NE-associated hematuria may. All patients in this study had hantavirus-specific IgG up to years after the infection. PMID:25533268

  19. Equilibrium and Kinetics of Sin Nombre Hantavirus Binding at DAF/CD55 Functionalized Bead Surfaces

    PubMed Central

    Buranda, Tione; Swanson, Scarlett; Bondu, Virginie; Schaefer, Leah; Maclean, James; Mo, Zhenzhen; Wycoff, Keith; Belle, Archana; Hjelle, Brian

    2014-01-01

    Decay accelerating factor (DAF/CD55) is targeted by many pathogens for cell entry. It has been implicated as a co-receptor for hantaviruses. To examine the binding of hantaviruses to DAF, we describe the use of Protein G beads for binding human IgG Fc domain-functionalized DAF ((DAF)2-Fc). When mixed with Protein G beads the resulting DAF beads can be used as a generalizable platform for measuring kinetic and equilibrium binding constants of DAF binding targets. The hantavirus interaction has high affinity (24–30 nM; kon ~ 105 M−1s−1, koff ~ 0.0045 s−1). The bivalent (DAF)2-Fc/SNV data agree with hantavirus binding to DAF expressed on Tanoue B cells (Kd = 14.0 nM). Monovalent affinity interaction between SNV and recombinant DAF of 58.0 nM is determined from competition binding. This study serves a dual purpose of presenting a convenient and quantitative approach of measuring binding affinities between DAF and the many cognate viral and bacterial ligands and providing new data on the binding constant of DAF and Sin Nombre hantavirus. Knowledge of the equilibrium binding constant allows for the determination of the relative fractions of bound and free virus particles in cell entry assays. This is important for drug discovery assays for cell entry inhibitors. PMID:24618810

  20. The adaptive immune response does not influence hantavirus disease or persistence in the Syrian hamster.

    PubMed

    Prescott, Joseph; Safronetz, David; Haddock, Elaine; Robertson, Shelly; Scott, Dana; Feldmann, Heinz

    2013-10-01

    Pathogenic New World hantaviruses cause severe disease in humans characterized by a vascular leak syndrome, leading to pulmonary oedema and respiratory distress with case fatality rates approaching 40%. Hantaviruses infect microvascular endothelial cells without conspicuous cytopathic effects, indicating that destruction of the endothelium is not a mechanism of disease. In humans, high levels of inflammatory cytokines are present in the lungs of patients that succumb to infection. This, along with other observations, suggests that disease has an immunopathogenic component. Currently the only animal model available to study hantavirus disease is the Syrian hamster, where infection with Andes virus (ANDV), the primary agent of disease in South America, results in disease that closely mimics that seen in humans. Conversely, inoculation of hamsters with a passaged Sin Nombre virus (SNV), the virus responsible for most cases of disease in North America, results in persistent infection with high levels of viral replication. We found that ANDV elicited a stronger innate immune response, whereas SNV elicited a more robust adaptive response in the lung. Additionally, ANDV infection resulted in significant changes in the blood lymphocyte populations. To determine whether the adaptive immune response influences infection outcome, we depleted hamsters of CD4(+) and CD8(+) T cells before infection with hantaviruses. Depletion resulted in inhibition of virus-specific antibody responses, although the pathogenesis and replication of these viruses were unaltered. These data show that neither hantavirus replication, nor pathogenesis caused by these viruses, is influenced by the adaptive immune response in the Syrian hamster. PMID:23600567

  1. Serological diagnosis of hantavirus pulmonary syndrome in a febrile patient in Colombia.

    PubMed

    Mattar, Salim; Garzon, Denisse; Tadeu, Luis; Faccini-Martínez, Alvaro A; Mills, James N

    2014-08-01

    Hantavirus pulmonary syndrome (HPS) is an often fatal rodent-borne zoonosis caused by any of at least 20 hantavirus genotypes distributed throughout the Americas. Although HPS has been documented in several bordering countries, it has not been reported in Colombia. Here we report seroconversion to a hantavirus in paired samples from a hospitalized patient with symptoms compatible with HPS from Montería, Córdoba Department, north-western Colombia. Tests for regionally endemic agents including Plasmodium, Leptospira, Salmonella, dengue virus, Brucella, Rickettsia, human immunodeficiency virus and hepatitis viruses were negative. Because the patient was enrolled in a clinical trial for hemorrhagic fevers conducted by the University of Córdoba, serum samples were collected on admission and at discharge. Testing using Sin Nombre virus ELISA showed IgG and IgM seroconversion between samples. The eventual finding of this first clinical case of hantavirus infection in Colombia is consistent with the high prevalence of hantavirus antibodies in humans in the region and the likely exposure of the patient to rodents. The clinical presentation was similar to that found in neighbouring Panama. PMID:24970702

  2. Coexistence of several novel hantaviruses in rodents indigenous to North America.

    PubMed

    Rowe, J E; St Jeor, S C; Riolo, J; Otteson, E W; Monroe, M C; Henderson, W W; Ksiazek, T G; Rollin, P E; Nichol, S T

    1995-10-20

    Three genetically distinct members of the Hantavirus genus have been detected in Nevada rodents by RT-PCR and nucleotide sequence analysis. These include Sin Nombre (SN), El Moro Canyon (ELMC), and Prospect Hill (PH)-like viruses which are primarily associated with Peromyscus maniculatus (deer mouse), Reithrodontomys megalotis (western harvest mouse), and Microtus spp. (voles), respectively. Although this region of the United States is ecologically diverse, rodents infected with different hantaviruses appear to coexist in several different geographical and ecological zones. In two widely separated states, Nevada and North Dakota, PH-like viruses are present in three different species of vole. In addition, ELMC-like virus has been detected in both R. megalotis and M. montanus (mountain vole). SN virus is a cause of hantavirus pulmonary syndrome throughout much of the United States. SN virus RNA is found in 12.5% of P. maniculatus in Nevada and eastern California. Two lineages of SN virus coexist in this region and differ from SN viruses originally found in infected rodents in New Mexico, Arizona, and Colorado. These data show the complexity of hantavirus maintenance in rodents. Distinct hantaviruses or virus lineages can coexist either in different or the same rodent species and in either different or the same geographic or ecological zones. PMID:7483255

  3. Phylogenetic and Geographical relationships of Hantavirus Strains in Eastern and Western Paraguay

    PubMed Central

    Chu, Yong-Kyu; Milligan, Brook; Owen, Robert D.; Goodin, Douglas G.; Jonsson, Colleen B.

    2009-01-01

    Recently, we reported the discovery of several potential rodent reservoirs of hantaviruses in western (Holochilus chacarius) and eastern Paraguay (Akodon montensis, Oligoryzomys chacoensis, and O. nigripes). Comparisons of the hantavirus S- and M-segments amplified from these four rodents revealed significant differences from each another and from other South American hantaviruses. The ALP strain from the semiarid Chaco ecoregion clustered with Leguna Negra and Rio Mamore (LN/RM), whereas the BMJ-ÑEB strain from the more humid lower Chaco ecoregion formed a clade with Oran and Bermejo. The other two strains, AAI and IP37/38, were distinct from known hantaviruses. With respect to the S-segment sequence, AAI from eastern Paraguay formed a clade with ALP/LN/RM, but its M-segment clustered with Pergamino and Maciel, suggesting a possible reassortment. AAI was found in areas experiencing rapid land cover fragmentation and change within the Interior Atlantic Forest. IP37/38 did not show any strong association with any of the known hantavirus strains. PMID:17172380

  4. The use of chimeric virus-like particles harbouring a segment of hantavirus Gc glycoprotein to generate a broadly-reactive hantavirus-specific monoclonal antibody.

    PubMed

    Zvirbliene, Aurelija; Kucinskaite-Kodze, Indre; Razanskiene, Ausra; Petraityte-Burneikiene, Rasa; Klempa, Boris; Ulrich, Rainer G; Gedvilaite, Alma

    2014-02-01

    Monoclonal antibodies (MAbs) against viral glycoproteins have important diagnostic and therapeutic applications. In most cases, the MAbs specific to viral glycoproteins are raised against intact virus particles. The biosynthesis of viral glycoproteins in heterologous expression systems such as bacteria, yeast, insect or mammalian cells is often problematic due to their low expression level, improper folding and limited stability. To generate MAbs against hantavirus glycoprotein Gc, we have used initially a recombinant yeast-expressed full-length Puumala virus (PUUV) Gc protein. However, this approach was unsuccessful. As an alternative recombinant antigen, chimeric virus-like particles (VLPs) harboring a segment of PUUV Gc glycoprotein were generated in yeast Saccharomyces cerevisiae. A 99 amino acid (aa)-long segment of Gc protein was inserted into the major capsid protein VP1 of hamster polyomavirus at previously defined positions: either site #1 (aa 80-89) or site #4 (aa 280-289). The chimeric proteins were found to self-assemble to VLPs as evidenced by electron microscopy. Chimeric VLPs induced an efficient insert-specific antibody response in immunized mice. Monoclonal antibody (clone #10B8) of IgG isotype specific to hantavirus Gc glycoprotein was generated. It recognized recombinant full-length PUUV Gc glycoprotein both in ELISA and Western blot assay and reacted specifically with hantavirus-infected cells in immunofluorescence assay. Epitope mapping studies revealed the N-terminally located epitope highly conserved among different hantavirus strains. In conclusion, our approach to use chimeric VLPs was proven useful for the generation of virus-reactive MAb against hantavirus Gc glycoprotein. The generated broadly-reactive MAb #10B8 might be useful for various diagnostic applications. PMID:24513568

  5. The Use of Chimeric Virus-like Particles Harbouring a Segment of Hantavirus Gc Glycoprotein to Generate a Broadly-Reactive Hantavirus-Specific Monoclonal Antibody

    PubMed Central

    Zvirbliene, Aurelija; Kucinskaite-Kodze, Indre; Razanskiene, Ausra; Petraityte-Burneikiene, Rasa; Klempa, Boris; Ulrich, Rainer G.; Gedvilaite, Alma

    2014-01-01

    Monoclonal antibodies (MAbs) against viral glycoproteins have important diagnostic and therapeutic applications. In most cases, the MAbs specific to viral glycoproteins are raised against intact virus particles. The biosynthesis of viral glycoproteins in heterologous expression systems such as bacteria, yeast, insect or mammalian cells is often problematic due to their low expression level, improper folding and limited stability. To generate MAbs against hantavirus glycoprotein Gc, we have used initially a recombinant yeast-expressed full-length Puumala virus (PUUV) Gc protein. However, this approach was unsuccessful. As an alternative recombinant antigen, chimeric virus-like particles (VLPs) harboring a segment of PUUV Gc glycoprotein were generated in yeast Saccharomyces cerevisiae. A 99 amino acid (aa)-long segment of Gc protein was inserted into the major capsid protein VP1 of hamster polyomavirus at previously defined positions: either site #1 (aa 80–89) or site #4 (aa 280–289). The chimeric proteins were found to self-assemble to VLPs as evidenced by electron microscopy. Chimeric VLPs induced an efficient insert-specific antibody response in immunized mice. Monoclonal antibody (clone #10B8) of IgG isotype specific to hantavirus Gc glycoprotein was generated. It recognized recombinant full-length PUUV Gc glycoprotein both in ELISA and Western blot assay and reacted specifically with hantavirus-infected cells in immunofluorescence assay. Epitope mapping studies revealed the N-terminally located epitope highly conserved among different hantavirus strains. In conclusion, our approach to use chimeric VLPs was proven useful for the generation of virus-reactive MAb against hantavirus Gc glycoprotein. The generated broadly-reactive MAb #10B8 might be useful for various diagnostic applications. PMID:24513568

  6. Distribution and abundance of sigmodontine rodents in relation to hantavirus in Neuquén, Argentina.

    PubMed

    Piudo, Luciana; Monteverde, Martín; González Capria, Silvana; Padula, Paula; Carmanchahi, Pablo

    2005-06-01

    In order to estimate spatial distribution, temporal variation, and prevalence of Andes hantavirus antibody in the rodent community, and especially in Oligoryzomys longicaudatus populations, four different ecosystems were trapped seasonally between spring 2001 and winter 2002 in Neuquen, northwestern Argentinean Patagonia. Five peridomestic settings were sampled within the same period. The rodent O. longicaudatus had the widest distribution in Neuquen, as it was the only species captured at every sample site except for the High Andean steppe, and it was also the most common species captured. Rodents of 13 species were tested for hantavirus antibody prevalence, but O. longicaudatus and Abrothrix longipilis were the only seropositive species. Seropositive individuals were captured during spring and summer in the Subantarctic forest and in winter 2001 in a peridomestic setting in the Patagonian steppe. The dominant presence of O. longicaudatus throughout Neuquen must be incorporated into strategies to prevent human exposure to hantavirus. PMID:16007965

  7. Tula virus: a newly detected hantavirus carried by European common voles.

    PubMed Central

    Plyusnin, A; Vapalahti, O; Lankinen, H; Lehväslaiho, H; Apekina, N; Myasnikov, Y; Kallio-Kokko, H; Henttonen, H; Lundkvist, A; Brummer-Korvenkontio, M

    1994-01-01

    A novel hantavirus has been discovered in European common voles, Microtus arvalis and Microtus rossiaemeridionalis. According to sequencing data for the genomic RNA S segment and nucleocapsid protein and data obtained by immunoblotting with a panel of monoclonal antibodies, the virus, designated Tula virus, is a distinct novel member of the genus Hantavirus. Phylogenetic analyses of Tula virus indicate that it is most closely related to Prospect Hill, Puumala, and Muerto Canyon viruses. The results support the view that the evolution of hantaviruses follows that of their primary carriers. Comparison of strains circulating within a local rodent population revealed a genetic drift via accumulation of base substitutions and deletions or insertions. The Tula virus population from individual animals is represented by quasispecies, indicating the potential for rapid evolution of the agent. Images PMID:7966573

  8. Isla Vista virus: a genetically novel hantavirus of the California vole Microtus californicus.

    PubMed

    Song, W; Torrez-Martinez, N; Irwin, W; Harrison, F J; Davis, R; Ascher, M; Jay, M; Hjelle, B

    1995-12-01

    Prospect Hill virus (PH) was isolated from a meadow vole (Microtus pennsylvanicus) in 1982, and much of its genome has been sequenced. Hantaviruses of other New World microtine rodents have not been genetically characterized. We show that another Microtus species (the California vole M. californicus) from the United States is host to a genetically distinct PH-like hantavirus, Isla Vista virus (ILV). The nucleocapsid protein of ILV differs from that of PH by 11.1% and a portion of the G2 glycoprotein differs from that of PH by 19.6%. ILV antibodies were identified in five of 33 specimens of M. californicus collected in 1975 and 1994-1995. Enzymatic amplification studies showed that 1975 and 1994-1995 ILV genomes were highly similar. Secondary infection of Peromyscus californicus was identified in Santa Barbara County, California. A long-standing enzootic of a genetically distinct hantavirus lineage is present in California voles. PMID:8847529

  9. Anjozorobe Hantavirus, a New Genetic Variant of Thailand Virus Detected in Rodents from Madagascar

    PubMed Central

    Razafindralambo, Nadia Kaloina; Lacoste, Vincent; Olive, Marie-Marie; Barivelo, Tony Andrianaivo; Soarimalala, Voahangy; Heraud, Jean-Michel; Lavergne, Anne

    2014-01-01

    Abstract Until now, there was only serological evidence that hantaviruses were circulating in rodents and infecting humans from Madagascar. To assess the presence of a hantavirus on the island, between October, 2008, and March, 2010, we sampled 585 rodents belonging to seven species in the Anjozorobe-Angavo forest corridor, 70 km north from the capital city Antananarivo. A hantavirus was detected from organs of the ubiquist roof rat (Rattus rattus) and of the endemic Major's tufted-tailed rat (Eliurus majori). Amazingly, sequence analysis of the S (small), M (medium), and L (large) coding DNA sequence of this virus showed that the Anjozorobe strain (proposed name) was a new genetic variant of Thailand virus (THAIV) that comprises other variants found in Southeast Asia. Because THAIV is suspected of causing hemorrhagic fever with renal syndrome in humans, ongoing studies are addressing the risk of infection by this new variant in the Malagasy population. PMID:24575755

  10. Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection.

    PubMed

    Rasmuson, J; Pourazar, J; Mohamed, N; Lejon, K; Evander, M; Blomberg, A; Ahlm, C

    2016-04-01

    Hantavirus infections may cause severe and sometime life-threatening lung failure. The pathogenesis is not fully known and there is an urgent need for effective treatment. We aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. Bronchoscopy with sampling of bronchoalveolar lavage (BAL) fluid was performed in 17 patients with acute Puumala hantavirus infection and 16 healthy volunteers acting as controls. Lymphocyte subsets, granzyme concentrations, and viral load were determined by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Analyses of BAL fluid revealed significantly higher numbers of activated CD8(+) T cells and natural killer (NK) cells, as well as higher concentrations of the cytotoxins granzymes A and B in hantavirus-infected patients, compared to controls. In patients, Puumala hantavirus RNA was detected in 88 % of BAL cell samples and correlated inversely to the T cell response. The magnitude of the pulmonary cytotoxic lymphocyte response correlated to the severity of disease and systemic organ dysfunction, in terms of need for supplemental oxygen treatment, hypotension, and laboratory data indicating renal failure, cardiac dysfunction, vascular leakage, and cell damage. Regulatory T cell numbers were significantly lower in patients compared to controls, and may reflect inadequate immune regulation during hantavirus infection. Hantavirus infection elicits a pronounced cytotoxic lymphocyte response in the lungs. The magnitude of the immune response was associated with disease severity. These results give insights into the pathogenesis and possibilities for new treatments. PMID:26873376

  11. Effect of Vandetanib on Andes virus survival in the hamster model of Hantavirus pulmonary syndrome.

    PubMed

    Bird, Brian H; Shrivastava-Ranjan, Punya; Dodd, Kimberly A; Erickson, Bobbie R; Spiropoulou, Christina F

    2016-08-01

    Hantavirus pulmonary syndrome (HPS) is a severe disease caused by hantavirus infection of pulmonary microvascular endothelial cells leading to microvascular leakage, pulmonary edema, pleural effusion and high case fatality. Previously, we demonstrated that Andes virus (ANDV) infection caused up-regulation of vascular endothelial growth factor (VEGF) and concomitant downregulation of the cellular adhesion molecule VE-cadherin leading to increased permeability. Analyses of human HPS-patient sera have further demonstrated increased circulating levels of VEGF. Here we investigate the impact of a small molecule antagonist of the VEGF receptor 2 (VEGFR-2) activation in vitro, and overall impact on survival in the Syrian hamster model of HPS. PMID:27233645

  12. The Experimental Research (In Vitro) of Carrageenans and Fucoidans to Decrease Activity of Hantavirus.

    PubMed

    Pavliga, Stanislav N; Kompanets, Galina G; Tsygankov, Vasiliy Yu

    2016-06-01

    The effect of carrageenans and fucoidans on the activity of Hantavirus is studied. It has been found that among carrageenans a significant antiviral effect is exerted by the ι-type, which decreases the viral titer by 2.5 log focus forming units per mL; among fucoidans, by a preparation from Laminaria cichorioides, which reduces the number of infected cells from 27.0 to 5.3 after pretreatment of both the macrophage culture and Hantavirus. The antiviral effect of fucoidan from Laminaria japonica is shown to grow in direct proportion to the increase of dose of the preparation. PMID:26943130

  13. Extinction of refugia of hantavirus infection in a spatially heterogeneous environment

    NASA Astrophysics Data System (ADS)

    Kumar, Niraj; Parmenter, R. R.; Kenkre, V. M.

    2010-07-01

    We predict an abrupt observable transition, on the basis of numerical studies, of hantavirus infection in terrain characterized by spatially dependent environmental resources. The underlying framework of the analysis is that of Fisher equations with an internal degree of freedom, the state of infection. The unexpected prediction is of the sudden disappearance of refugia of infection in spite of the existence of supercritical (favorable) food resources, brought about by reduction of their spatial extent. Numerical results are presented and a theoretical explanation is provided on analytic grounds on the basis of the competition of diffusion of rodents carrying the hantavirus and nonlinearity present in the resource interactions.

  14. Dahonggou Creek virus, a divergent lineage of hantavirus harbored by the long-tailed mole (Scaptonyx fusicaudus).

    PubMed

    Kang, Hae Ji; Gu, Se Hun; Cook, Joseph A; Yanagihara, Richard

    2016-01-01

    Novel hantaviruses, recently detected in moles (order Eulipotyphla, family Talpidae) from Europe, Asia, and North America would predict a broader host range and wider ecological diversity. Employing RT-PCR, archival frozen tissues from the Chinese shrew mole (Uropsilus soricipes), broad-footed mole (Scapanus latimanus), coast mole (Scapanus orarius), Townsend's mole (Scapanus townsendii), and long-tailed mole (Scaptonyx fusicaudus) were analyzed for hantavirus RNA. Following multiple attempts, a previously unrecognized hantavirus, designated Dahonggou Creek virus (DHCV), was detected in a long-tailed mole, captured in Shimian County, Sichuan Province, People's Republic of China, in August 1989. Analyses of a 1058-nucleotide region of the RNA-dependent RNA polymerase-encoding L segment indicated that DHCV was genetically distinct from other rodent-, shrew-, mole-, and bat-borne hantaviruses. Phylogenetic trees, using maximum likelihood and Bayesian methods, showed that DHCV represented a divergent lineage comprising crocidurine and myosoricine shrew-borne hantaviruses. Although efforts to obtain the S- and M-genomic segments failed, the L-segment sequence analysis, reported here, expands the genetic database of non-rodent-borne hantaviruses. Also, by further mining natural history collections of archival specimens, the genetic diversity of hantaviruses will elucidate their evolutionary origins. PMID:27433135

  15. NK Cell Activation in Human Hantavirus Infection Explained by Virus-Induced IL-15/IL15Rα Expression

    PubMed Central

    Braun, Monika; Björkström, Niklas K.; Gupta, Shawon; Sundström, Karin; Ahlm, Clas; Klingström, Jonas; Ljunggren, Hans-Gustaf

    2014-01-01

    Clinical infection with hantaviruses cause two severe acute diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These diseases are characterized by strong immune activation, increased vascular permeability, and up to 50% case-fatality rates. One prominent feature observed in clinical hantavirus infection is rapid expansion of natural killer (NK) cells in peripheral blood of affected individuals. We here describe an unusually high state of activation of such expanding NK cells in the acute phase of clinical Puumala hantavirus infection. Expanding NK cells expressed markedly increased levels of activating NK cell receptors and cytotoxic effector molecules. In search for possible mechanisms behind this NK cell activation, we observed virus-induced IL-15 and IL-15Rα on infected endothelial and epithelial cells. Hantavirus-infected cells were shown to strongly activate NK cells in a cell-cell contact-dependent way, and this response was blocked with anti-IL-15 antibodies. Surprisingly, the strength of the IL-15-dependent NK cell response was such that it led to killing of uninfected endothelial cells despite expression of normal levels of HLA class I. In contrast, hantavirus-infected cells were resistant to NK cell lysis, due to a combination of virus-induced increase in HLA class I expression levels and hantavirus-mediated inhibition of apoptosis induction. In summary, we here describe a possible mechanism explaining the massive NK cell activation and proliferation observed in HFRS patients caused by Puumala hantavirus infection. The results add further insights into mechanisms behind the immunopathogenesis of hantavirus infections in humans and identify new possible targets for intervention. PMID:25412359

  16. Sin Nombre hantavirus decreases survival of male deer mice.

    PubMed

    Luis, Angela D; Douglass, Richard J; Hudson, Peter J; Mills, James N; Bjørnstad, Ottar N

    2012-06-01

    How pathogens affect their hosts is a key question in infectious disease ecology, and it can have important influences on the spread and persistence of the pathogen. Sin Nombre virus (SNV) is the etiological agent of hantavirus pulmonary syndrome (HPS) in humans. A better understanding of SNV in its reservoir host, the deer mouse, could lead to improved predictions of the circulation and persistence of the virus in the mouse reservoir, and could help identify the factors that lead to increased human risk of HPS. Using mark-recapture statistical modeling on longitudinal data collected over 15 years, we found a 13.4% decrease in the survival of male deer mice with antibodies to SNV compared to uninfected mice (both male and female). There was also an additive effect of breeding condition, with a 21.3% decrease in survival for infected mice in breeding condition compared to uninfected, non-breeding mice. The data identified that transmission was consistent with density-dependent transmission, implying that there may be a critical host density below which SNV cannot persist. The notion of a critical host density coupled with the previously overlooked disease-induced mortality reported here contribute to a better understanding of why SNV often goes extinct locally and only seems to persist at the metapopulation scale, and why human spillover is episodic and hard to predict. PMID:22218940

  17. Competitive Homogeneous Immunoassay for Rapid Serodiagnosis of Hantavirus Disease

    PubMed Central

    Rusanen, Juuso; Hepojoki, Jussi; Nurmi, Visa; Vaheri, Antti; Lundkvist, Åke; Hedman, Klaus; Vapalahti, Olli

    2015-01-01

    In this study, we describe a competitive homogeneous immunoassay that makes use of Förster resonance energy transfer (FRET) in rapid detection of pathogen-specific antibodies. The assay principle is based on competition between a monoclonal antibody (MAb) and serum antibodies to a given antigen. In the assay, named competitive FRET immunoassay (CFRET-IA), the FRET signal is induced if MAb carrying a donor label binds to an acceptor-labeled antigen. Specific antibodies in serum compete for antigen binding, resulting in reduced FRET signal. The proof-of-principle for the assay was obtained using donor-labeled Puumala virus nucleocapsid protein (PUUV-N) and acceptor-labeled anti-PUUV-N MAb. The assay was evaluated by analyzing 329 clinical samples comprising 101 from individuals with acute PUUV infection, 42 from individuals with past infection, and 186 from individuals with PUUV-seronegative sera, and the results were compared to those of reference tests. The rapid serodiagnostic test we introduced herein performed with 100% sensitivity and 99% specificity for diagnosing acute hantavirus disease. PMID:25972427

  18. Characterization of Puumala hantavirus in bank voles from two regions in the Netherlands where human cases occurred.

    PubMed

    de Vries, A; Vennema, H; Bekker, D L; Maas, M; Adema, J; Opsteegh, M; van der Giessen, J W B; Reusken, C B E M

    2016-07-01

    Puumala hantavirus (PUUV) is the most common and widespread hantavirus in Europe and is associated with a mild form of haemorrhagic fever with renal syndrome in humans, called nephropathia epidemica. This study presents the molecular characterization of PUUV circulating in bank voles in two regions of the Netherlands. Most human cases of hantavirus infection are from these two regions. Phylogenetic analysis of the (partial) S, M and L-segments indicated that the Dutch strains belong to the CE lineage, which includes PUUV strains from France, Germany and Belgium. We have identified two distinct groups of PUUV, corresponding with their geographic origin and with adjoining regions in neighbouring countries. PMID:27075118

  19. New ecological aspects of hantavirus infection: a change of a paradigm and a challenge of prevention--a review.

    PubMed

    Zeier, Martin; Handermann, Michaela; Bahr, Udo; Rensch, Baldur; Müller, Sandra; Kehm, Roland; Muranyi, Walter; Darai, Gholamreza

    2005-03-01

    In the last decades a significant number of so far unknown or underestimated pathogens have emerged as fundamental health hazards of the human population despite intensive research and exceptional efforts of modern medicine to embank and eradicate infectious diseases. Almost all incidents caused by such emerging pathogens could be ascribed to agents that are zoonotic or expanded their host range and crossed species barriers. Many different factors influence the status of a pathogen to remain unnoticed or evolves into a worldwide threat. The ability of an infectious agent to adapt to changing environmental conditions and variations in human behavior, population development, nutrition, education, social, and health status are relevant factors affecting the correlation between pathogen and host. Hantaviruses belong to the emerging pathogens having gained more and more attention in the last decades. These viruses are members of the family Bunyaviridae and are grouped into a separate genus known as Hantavirus. The serotypes Hantaan (HTN), Seoul (SEO), Puumala (PUU), and Dobrava (DOB) virus predominantly cause hemorrhagic fever with renal syndrome (HFRS), a disease characterized by renal failure, hemorrhages, and shock. In the recent past, many hantavirus isolates have been identified and classified in hitherto unaffected geographic regions in the New World (North, Middle, and South America) with characteristic features affecting the lungs of infected individuals and causing an acute pulmonary syndrome. Hantavirus outbreaks in the United States of America at the beginning of the 10th decade of the last century fundamentally changed our knowledge about the appearance of the hantavirus specific clinical picture, mortality, origin, and transmission route in human beings. The hantavirus pulmonary syndrome (HPS) was first recognized in 1993 in the Four Corners Region of the United States and had a lethality of more than 50%. Although the causative virus was first termed in

  20. Characterization of cross-reactive and serotype-specific epitopes on the nucleocapsid proteins of hantaviruses.

    PubMed

    Tischler, Nicole D; Rosemblatt, Mario; Valenzuela, Pablo D T

    2008-07-01

    The hantavirus nucleocapsid (N) protein fulfills several key roles in virus replication and assembly and is the major antigen in humoral immune responses in humans and mice. Here we report on epitopes involved in serotype-specific and cross-reactive recognition of the N proteins of hantaviruses using monoclonal antibodies (mAbs) against the N proteins of Andes virus (ANDV) and Sin Nombre virus (SNV). The mAbs define at least twelve different epitopic patterns which span eight sequences, including amino acids 17-59, 66-78, 79-91, 157-169, 222-234, 244-263, 274-286 and 326-338 on the SNV and ANDV N proteins. Studies on the cross-reactivity of these mAbs with different hantavirus N proteins indicated that epitopes located within amino acids 244-286 are related to serotype specificity. We analyzed further the location of epitopes with available three-dimensional structure information including the N-terminal coiled-coil and derived exposed and hidden residues of these epitopes. The generated recombinant N proteins and the characterized mAbs are functional tools being now available for hantavirus diagnostics and replication studies. PMID:18342973

  1. A Cluster of Three Cases of Hantavirus Pulmonary Syndrome among Canadian Military Personnel.

    PubMed

    Parkes, Leighanne O; Nguyen, Trong Tien; Longtin, Jean; Beaudoin, Marie-Claude; Bestman-Smith, Julie; Vinh, Donald C; Boivin, Guy; Loo, Vivian G

    2016-01-01

    Hantavirus pulmonary syndrome (HPS) is a rare illness in eastern Canada. We present three cases of HPS among military personnel in Quebec. The three cases shared a common exposure to mouse excreta while engaged in military training in Alberta, a western province of Canada. PMID:27366160

  2. Isolation of sochi virus from a fatal case of hantavirus disease with fulminant clinical course.

    PubMed

    Dzagurova, Tamara K; Witkowski, Peter T; Tkachenko, Evgeniy A; Klempa, Boris; Morozov, Vyacheslav G; Auste, Brita; Zavora, Dmitriy L; Iunicheva, Iulia V; Mutnih, Elena S; Kruger, Detlev H

    2012-01-01

    Sochi virus, a novel genetic variant of Dobrava-Belgrade virus, was isolated in cell culture from a fulminant lethal case of hantavirus disease presenting with shock and combined kidney and lung failure. Sochi virus is transmitted to humans from host reservoir Apodemus ponticus and must be considered a life-threatening emerging agent. PMID:22042875

  3. Molecular method for the detection of Andes hantavirus infection: validation for clinical diagnostics.

    PubMed

    Vial, Cecilia; Martinez-Valdebenito, Constanza; Rios, Susana; Martinez, Jessica; Vial, Pablo A; Ferres, Marcela; Rivera, Juan C; Perez, Ruth; Valdivieso, Francisca

    2016-01-01

    Hantavirus cardiopulmonary syndrome is a severe disease caused by exposure to New World hantaviruses. Early diagnosis is difficult due to the lack of specific initial symptoms. Antihantavirus antibodies are usually negative until late in the febrile prodrome or the beginning of cardiopulmonary phase, while Andes hantavirus (ANDV) RNA genome can be detected before symptoms onset. We analyzed the effectiveness of quantitative reverse transcription polymerase chain reaction (RT-qPCR) as a diagnostic tool detecting ANDV-Sout genome in peripheral blood cells from 78 confirmed hantavirus patients and 166 negative controls. Our results indicate that RT-qPCR had a low detection limit (~10 copies), with a specificity of 100% and a sensitivity of 94.9%. This suggests the potential for establishing RT-qPCR as the assay of choice for early diagnosis, promoting early effective care of patients, and improving other important aspects of ANDV infection management, such as compliance of biosafety recommendations for health personnel in order to avoid nosocomial transmission. PMID:26508102

  4. Successful treatment of severe hantavirus nephritis with corticosteroids: a case report and literature review.

    PubMed

    Martinuč Bergoč, Maja; Lindič, Jelka; Kovač, Damjan; Ferluga, Dušan; Pajek, Jernej

    2013-08-01

    Hantaviruses can be associated with severe form of hemorrhagic fever with renal syndrome although there are only a few cases reporting chronic kidney disease after hantavirus infection. We report a severe nonresolving chronic renal failure after protracted Dobrava hantavirus infection successfully treated with corticosteroids. Ten days after working in a basement a 33-year-old man fell seriously ill, with high fever, chills, diffuse myalgia, headache and abdominal pain. After hospital admission a diagnosis of hemorrhagic fever with renal syndrome caused by Dobrava hantavirus was made. Acute oliguric kidney injury developed in the first 3 days after admission, in a few days diuresis restored and he became polyuric. Nevertheless renal failure persisted and he needed hemodialysis. Because of nonresolving kidney failure, nephrogenic diabetes insipidus and renoparenchymal arterial hypertension persisting 2 months after onset of symptoms, a kidney biopsy was performed, showing severe necrotizing tubulointerstitial nephritis. High dose methylprednisolone therapy was started and his renal function significantly improved. Two months later a second renal biopsy showed persisting elements of active necrotizing tubulointerstitial nephritis. We decided to stop corticosteroid treatment and introduced aldosterone antagonist eplerenon as anti-fibrotic agent, and his renal function further improved and remained stable. Nine months later his serum creatinine concentration was 227 μmol/L, proteinuria 0.156 g/day and well controlled nephrogenic diabetes insipidus. PMID:23931879

  5. A Cluster of Three Cases of Hantavirus Pulmonary Syndrome among Canadian Military Personnel

    PubMed Central

    Parkes, Leighanne O.; Nguyen, Trong Tien; Longtin, Jean; Beaudoin, Marie-Claude; Bestman-Smith, Julie; Vinh, Donald C.; Boivin, Guy; Loo, Vivian G.

    2016-01-01

    Hantavirus pulmonary syndrome (HPS) is a rare illness in eastern Canada. We present three cases of HPS among military personnel in Quebec. The three cases shared a common exposure to mouse excreta while engaged in military training in Alberta, a western province of Canada. PMID:27366160

  6. Circulation of hantaviruses in the influence area of the Cuiabá-Santarém Highway.

    PubMed

    Medeiros, Daniele B A; da Rosa, Elizabeth S Travassos; Marques, Aparecido A R; Simith, Darlene B; Carneiro, Adriana R; Chiang, Jannifer O; Prazeres, Ivy T E; Vasconcelos, Pedro F C; Nunes, Márcio R T

    2010-08-01

    We describe evidence of circulation of hantaviruses in the influence area of the Santarém-Cuiabá Highway (BR-163) in the Brazilian Amazon through the prevalence of specific antibodies against hantaviruses in inhabitants living in four municipalities of this area: Novo Progresso (2.16%) and Trairão (4.37%), in state of Pará (PA), and Gua-rantã do Norte (4.74%) and Marcelândia (9.43%), in state of Mato Grosso. We also demonstrate the ongoing association between Castelo dos Sonhos virus (CASV) and hantavirus pulmonary syndrome (HPS) cases in the Castelo dos Sonhos district (municipality of Altamira, PA) and the first report of CASV in the municipalities of Novo Progresso and Guarantã do Norte. The results of this work highlight the risk for a possible increase in the number of HPS cases and the emergence of new hantavirus lineages associated with deforestation in this Amazonian area after the conclusion of paving works on BR-163 Highway. PMID:20835614

  7. Genetic Diversity of Thottapalayam Virus, a Hantavirus Harbored by the Asian House Shrew (Suncus murinus) in Nepal

    PubMed Central

    Kang, Hae Ji; Kosoy, Michael Y.; Shrestha, Sanjaya K.; Shrestha, Mrigendra P.; Pavlin, Julie A.; Gibbons, Robert V.; Yanagihara, Richard

    2011-01-01

    Despite the recent discovery of genetically divergent hantaviruses in shrews of multiple species in widely separated geographic regions, data are unavailable about the genetic diversity and phylogeography of Thottapalayam virus (TPMV), a hantavirus originally isolated from an Asian house shrew (Suncus murinus) captured in southern India more than four decades ago. To bridge this knowledge gap, the S, M, and L segments of hantavirus RNA were amplified by reverse transcription polymerase chain reaction from archival lung tissues of Asian house shrews captured in Nepal from January to September 1996. Pair-wise alignment and comparison revealed approximately 80% nucleotide and > 94% amino acid sequence similarity to prototype TPMV. Phylogenetic analyses, generated by maximum likelihood and Bayesian methods, showed geographic-specific clustering of TPMV, similar to that observed for rodent- and soricid-borne hantaviruses. These findings confirm that the Asian house shrew is the natural reservoir of TPMV and suggest a long-standing virus–host relationship. PMID:21896819

  8. Development of an immunochromatography strip test based on truncated nucleocapsid antigens of three representative hantaviruses

    PubMed Central

    2014-01-01

    Background Hantaviruses are causative agents of hemorrhagic fever with renal syndrome (HFRS) and nephropathia epidemica (NE) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. There is a need for time-saving diagnostic methods. In the present study, recombinant N antigens were used as antigens in an immunochromatography strip (ICG) test to detect specific IgG antibodies. Methods The N-terminal 103 amino acids (aa) of Hantaan virus (HTNV), Puumala virus (PUUV) and Andes virus (ANDV) nucleocapsid (N) protein were expressed in E. coli as representative antigens of three groups (HFRS, NE and HPS-causing viruses) of hantavirus. Five different types of ICG test strips, one antigen line on one strip for each of the three selected hantaviruses (HTNV, PUUV and ANDV), three antigen lines on one strip and a mixed antigen line on one strip, were developed and sensitivities were compared. Results A total of 87 convalescent-phase patient sera, including sera from 35 HFRS patients, 36 NE patients and 16 HPS patients, and 25 sera from healthy seronegative people as negative controls were used to evaluate the ICG test. Sensitivities of the three-line strip and mixed-line strip were similar to those of the single antigen strip (97.2 to 100%). On the other hand, all of the ICG test strips showed high specificities to healthy donors. Conclusion These results indicated that the ICG test with the three representative antigens is an effective serodiagnostic tool for screening and typing of hantavirus infection in humans. PMID:24885901

  9. Cross-Protection against Challenge with Puumala Virus after Immunization with Nucleocapsid Proteins from Different Hantaviruses

    PubMed Central

    de Carvalho Nicacio, Cristina; Gonzalez Della Valle, Marcelo; Padula, Paula; Björling, Ewa; Plyusnin, Alexander; Lundkvist, Åke

    2002-01-01

    Hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome in humans. The nucleocapsid protein (N) is relatively conserved among hantaviruses and highly immunogenic in both laboratory animals and humans, and it has been shown to induce efficient protective immunity in animal models. To investigate the ability of recombinant N (rN) from different hantaviruses to elicit cross-protection, we immunized bank voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized with PUUV and TOPV rN were completely protected. In the group immunized with DOBV rN, 7 of 10 animals were protected, while only 3 of 8 animals were protected in the group immunized with ANDV rN, which is more closely related to PUUV rN than DOBV rN. Humoral and cellular immune responses after rN immunization were also investigated. The highest cross-reactive humoral responses against PUUV antigen were detected in sera from ANDV rN-immunized animals, followed by those from TOPV rN-immunized animals, and only very low antibody cross-reactivity was observed in sera from DOBV rN-immunized animals. In proliferation assays, T lymphocytes from animals immunized with all heterologous rNs were as efficiently recalled in vitro by PUUV rN as were T lymphocytes from animals immunized with homologous protein. In summary, this study has shown that hantavirus N can elicit cross-protective immune responses against PUUV, and the results suggest a more important role for the cellular arm of the immune response than for the humoral arm in cross-protection elicited by rN. PMID:12050380

  10. Two clinical cases of renal syndrome caused by Dobrava/Saaremaa hantaviruses imported to the Netherlands from Poland and Belarus, 2012–2014

    PubMed Central

    GeurtsvanKessel, Corine H.; Goeijenbier, Marco; Verner-Carlsson, Jenny; Litjens, Eline; Bos, Willem-Jan; Pas, Suzan D.; Medonça Melo, Mariana; Koopmans, Marion; Lundkvist, Åke; Reusken, Chantal B. E. M.

    2016-01-01

    We report the rare event of two imported cases in the Netherlands presenting with renal syndrome caused by Dobrava (DOBV)/Saaremaa (SAAV) hantaviruses. DOBV/SAAV hantaviruses are not circulating in the Netherlands and their clinical manifestation is typically more severe than that of the endemic Puumala virus (PUUV). This report aims to increase awareness among healthcare professionals and diagnostic laboratories to consider different hantaviruses as a cause of renal failure. PMID:26818411

  11. Two clinical cases of renal syndrome caused by Dobrava/Saaremaa hantaviruses imported to the Netherlands from Poland and Belarus, 2012-2014.

    PubMed

    GeurtsvanKessel, Corine H; Goeijenbier, Marco; Verner-Carlsson, Jenny; Litjens, Eline; Bos, Willem-Jan; Pas, Suzan D; Melo, Mariana Medonça; Koopmans, Marion; Lundkvist, Åke; Reusken, Chantal B E M

    2016-01-01

    We report the rare event of two imported cases in the Netherlands presenting with renal syndrome caused by Dobrava (DOBV)/Saaremaa (SAAV) hantaviruses. DOBV/SAAV hantaviruses are not circulating in the Netherlands and their clinical manifestation is typically more severe than that of the endemic Puumala virus (PUUV). This report aims to increase awareness among healthcare professionals and diagnostic laboratories to consider different hantaviruses as a cause of renal failure. PMID:26818411

  12. Beneficios y riesgos de la terapia estrogénica en la menopausia varían por edad, de acuerdo con el e

    Cancer.gov

    Los datos de seguimiento a largo plazo del estudio Iniciativa para la Salud de la Mujer (WHI) proporcionan información nueva e importante sobre los posibles riesgos y beneficios de la terapia hormonal para tratar síntomas relacionadas con la menopausia.

  13. Resultado negativo de prueba del VPH es mejor predictor de riesgo bajo de cáncer de cuello uterino

    Cancer.gov

    De acuerdo con un estudio en el que participaron más de un millón de mujeres, los investigadores del NCI han determinado que el resultado negativo de una prueba para la detección del VPH proporciona mayor certeza o seguridad frente a riesgos futuros de cá

  14. Hantavirus (Bunyaviridae) infections in rodents from Orange and San Diego counties, California.

    PubMed

    Bennett, S G; Webb, J P; Madon, M B; Childs, J E; Ksiazek, T G; Torrez-Martinez, N; Hjelle, B

    1999-01-01

    During a screening program to determine the extent of hantavirus activity in Orange and San Diego Counties, California, serum samples from 2,365 rodents representing nine genera and 15 species were tested for hantavirus antibodies. A reverse transcription-polymerase chain reaction on selected seropositive rodents was used to identify the specific hantavirus. Rodents positive for Sin Nombre virus (SNV) antibodies by Western blot included 86 (9.1%) of 948 deer mice (Peromyscus maniculatus), four (1.5%) of 275 California mice (Peromyscus californicus), one (0.5%) of 196 cactus mice (Peromyscus eremicus), 51 (12.2%) of 417 harvest mice (Reithrodontomys megalotis), and five (12.5%) of 40 California voles (Microtus californicus). All other specimens tested were negative for hantavirus antibodies. There was a correlation between age and sex of the reservoir host and prevalence of SNV antibody, especially among male deer mice and harvest mice. Few seasonal trends in antibody prevalence were observed and continued maintenance of SNV and El Moro Canyon virus was found at several foci over a 4-5-year period. Isla Vista virus was also found in voles and represents the first recorded in Orange County. Microhabitat selection on the part of these rodents based on plant density, plant height, and availability of food plants may explain, to some extent, all of the hantavirus-positive foci throughout the study area over a broad geographic range and the lack of antibody-positive rodents in dense chaparral, woodland, and riparian areas. The majority of rodents positive for SNV was identified from localities along coastal bluffs and the foothills of the Santa Ana Mountains, where trap success was high and P. maniculatus represented 43% of all rodents collected. Several residential, commercial, and industrial sites exist in these areas and the potential health risk should not be overlooked. This study represents an in-depth analysis of the prevalence, host distribution, and

  15. Molecular evolution of Azagny virus, a newfound hantavirus harbored by the West African pygmy shrew (Crocidura obscurior) in Côte d'Ivoire

    PubMed Central

    2011-01-01

    Background Tanganya virus (TGNV), the only shrew-associated hantavirus reported to date from sub-Saharan Africa, is harbored by the Therese's shrew (Crocidura theresae), and is phylogenetically distinct from Thottapalayam virus (TPMV) in the Asian house shrew (Suncus murinus) and Imjin virus (MJNV) in the Ussuri white-toothed shrew (Crocidura lasiura). The existence of myriad soricid-borne hantaviruses in Eurasia and North America would predict the presence of additional hantaviruses in sub-Saharan Africa, where multiple shrew lineages have evolved and diversified. Methods Lung tissues, collected in RNAlater®, from 39 Buettikofer's shrews (Crocidura buettikoferi), 5 Jouvenet's shrews (Crocidura jouvenetae), 9 West African pygmy shrews (Crocidura obscurior) and 21 African giant shrews (Crocidura olivieri) captured in Côte d'Ivoire during 2009, were systematically examined for hantavirus RNA by RT-PCR. Results A genetically distinct hantavirus, designated Azagny virus (AZGV), was detected in the West African pygmy shrew. Phylogenetic analysis of the S, M and L segments, using maximum-likelihood and Bayesian methods, under the GTR+I+Γ model of evolution, showed that AZGV shared a common ancestry with TGNV and was more closely related to hantaviruses harbored by soricine shrews than to TPMV and MJNV. That is, AZGV in the West African pygmy shrew, like TGNV in the Therese's shrew, did not form a monophyletic group with TPMV and MJNV, which were deeply divergent and basal to other rodent- and soricomorph-borne hantaviruses. Ancestral distributions of each hantavirus lineage, reconstructed using Mesquite 2.74, suggested that the common ancestor of all hantaviruses was most likely of Eurasian, not African, origin. Conclusions Genome-wide analysis of many more hantaviruses from sub-Saharan Africa are required to better understand how the biogeographic origin and radiation of African shrews might have contributed to, or have resulted from, the evolution of hantaviruses

  16. Human seroprevalence indicating hantavirus infections in tropical rainforests of Côte d’Ivoire and Democratic Republic of Congo

    PubMed Central

    Witkowski, Peter T.; Leendertz, Siv A. J.; Auste, Brita; Akoua-Koffi, Chantal; Schubert, Grit; Klempa, Boris; Muyembe-Tamfum, Jean-Jacques; Karhemere, Stomy; Leendertz, Fabian H.; Krüger, Detlev H.

    2015-01-01

    Hantaviruses are members of the Bunyaviridae family carried by small mammals and causing human hemorrhagic fevers worldwide. In Western Africa, where a variety of hemorrhagic fever viruses occurs, indigenous hantaviruses have been molecularly found in animal reservoirs such as rodents, shrews, and bats since 2006. To investigate the human contact to hantaviruses carried by these hosts and to assess the public health relevance of hantaviruses for humans living in the tropical rainforest regions of Western and Central Africa, we performed a cross-sectional seroprevalence study in the region of Taï National Park in Côte d’Ivoire and the Bandundu region near the Salonga National Park in the Democratic Republic (DR) of Congo. Serum samples were initially screened with enzyme-linked immunosorbent assays using nucleoproteins of several hantaviruses as diagnostic antigens. Positive results were confirmed by Western blotting and immunofluorescence testing. Seroprevalence rates of 3.9% (27/687) and 2.4% (7/295), respectively, were found in the investigated regions in Côte d’Ivoire and the DR Congo. In Côte d’Ivoire, this value was significantly higher than the seroprevalence rates previously reported from the neighboring country Guinea as well as from South Africa. Our study indicates an exposure of humans to hantaviruses in West and Central African tropical rainforest areas. In order to pinpoint the possible existence and frequency of clinical disease caused by hantaviruses in this region of the world, systematic investigations of patients with fever and renal or respiratory symptoms are required. PMID:26052326

  17. New Genetic Lineage of Tula Hantavirus in Microtus arvalis obscurus in Eastern Kazakhstan

    PubMed Central

    Plyusnina, Angelina; Laakkonen, Juha; Niemimaa, Jukka; Henttonen, Heikki; Plyusnin, Alexander

    2008-01-01

    Genomic sequences of Tula (TULV) hantavirus were recovered from tissue samples of European common voles Microtus arvalis (subspecies obscurus) captured in Kazakhstan, Central Asia. Phylogenetic analysis of the S genomic segment of Kazakh TULV strains showed that they form distinct, well supported genetic lineage and share a more ancient common ancestor with two Russian lineages of TULV. The deduced sequence of the nucleocapsid (N) protein of Kazakh TULV strains carried specific amino acid signature: T274Q276T281. The Microtus arvalis group includes several sibling species and/or subspecies in Eurasia, indicating recent and ongoing evolutionary radiation. Our data on TULV lineages in Central Asia, the region not studied for hantaviruses earlier, highlight the diversity of both Microtus host and the virus and also their co-evolution. PMID:19440462

  18. Divergent ancestral lineages of newfound hantaviruses harbored by phylogenetically related crocidurine shrew species in Korea

    PubMed Central

    Arai, Satoru; Gu, Se Hun; Baek, Luck Ju; Tabara, Kenji; Bennett, Shannon; Oh, Hong-Shik; Takada, Nobuhiro; Kang, Hae Ji; Tanaka-Taya, Keiko; Morikawa, Shigeru; Okabe, Nobuhiko; Yanagihara, Richard; Song, Jin-Won

    2012-01-01

    Spurred by the recent isolation of a novel hantavirus, named Imjin virus (MJNV), from the Ussuri white-toothed shrew (Crocidura lasiura), targeted trapping was conducted for the phylogenetically related Asian lesser white-toothed shrew (Crocidura shantungensis). Pair-wise alignment and comparison of the S, M and L segments of a newfound hantavirus, designated Jeju virus (JJUV), indicated remarkably low nucleotide and amino acid sequence similarity with MJNV. Phylogenetic analyses, using maximum likelihood and Bayesian methods, showed divergent ancestral lineages for JJUV and MJNV, despite the close phylogenetic relationship of their reservoir soricid hosts. Also, no evidence of host switching was apparent in tanglegrams, generated by TreeMap 2.0β. PMID:22230701

  19. Were the English sweating sickness and the Picardy sweat caused by hantaviruses?

    PubMed

    Heyman, Paul; Simons, Leopold; Cochez, Christel

    2014-01-01

    The English sweating sickness caused five devastating epidemics between 1485 and 1551, England was hit hardest, but on one occasion also mainland Europe, with mortality rates between 30% and 50%. The Picardy sweat emerged about 150 years after the English sweat disappeared, in 1718, in France. It caused 196 localized outbreaks and apparently in its turn disappeared in 1861. Both diseases have been the subject of numerous attempts to define their origin, but so far all efforts were in vain. Although both diseases occurred in different time frames and were geographically not overlapping, a common denominator could be what we know today as hantavirus infections. This review aims to shed light on the characteristics of both diseases from contemporary as well as current knowledge and suggests hantavirus infection as the most likely cause for the English sweating sickness as well as for the Picardy sweat. PMID:24402305

  20. Were the English Sweating Sickness and the Picardy Sweat Caused by Hantaviruses?

    PubMed Central

    Heyman, Paul; Simons, Leopold; Cochez, Christel

    2014-01-01

    The English sweating sickness caused five devastating epidemics between 1485 and 1551, England was hit hardest, but on one occasion also mainland Europe, with mortality rates between 30% and 50%. The Picardy sweat emerged about 150 years after the English sweat disappeared, in 1718, in France. It caused 196 localized outbreaks and apparently in its turn disappeared in 1861. Both diseases have been the subject of numerous attempts to define their origin, but so far all efforts were in vain. Although both diseases occurred in different time frames and were geographically not overlapping, a common denominator could be what we know today as hantavirus infections. This review aims to shed light on the characteristics of both diseases from contemporary as well as current knowledge and suggests hantavirus infection as the most likely cause for the English sweating sickness as well as for the Picardy sweat. PMID:24402305

  1. Stage-dependent model for Hantavirus infection: The effect of the initial infection-free period

    NASA Astrophysics Data System (ADS)

    Reinoso, José A.; de la Rubia, F. Javier

    2013-04-01

    We propose a stage-dependent model with constant delay to study the effect of the initial infection-free period on the spread of Hantavirus infection in rodents. We analyze the model under various extreme weather conditions, in the context of the El Niño-La Niña Southern Oscillation phenomenon, and show how these variations determine the evolution of the system significantly. When the scenario corresponds to El Niño, the system presents a demographic explosion and a delayed outbreak of Hantavirus infection, whereas if the scenario is the opposite there is a rapid decline of the population, but with a possible persistence period that may imply a considerable risk for public health, a fact that is in agreement with available field data. We use the model to simulate a historical evolution that resembles the processes that occurred in the 1990s.

  2. Stage-dependent model for Hantavirus infection: the effect of the initial infection-free period.

    PubMed

    Reinoso, José A; de la Rubia, F Javier

    2013-04-01

    We propose a stage-dependent model with constant delay to study the effect of the initial infection-free period on the spread of Hantavirus infection in rodents. We analyze the model under various extreme weather conditions, in the context of the El Niño-La Niña Southern Oscillation phenomenon, and show how these variations determine the evolution of the system significantly. When the scenario corresponds to El Niño, the system presents a demographic explosion and a delayed outbreak of Hantavirus infection, whereas if the scenario is the opposite there is a rapid decline of the population, but with a possible persistence period that may imply a considerable risk for public health, a fact that is in agreement with available field data. We use the model to simulate a historical evolution that resembles the processes that occurred in the 1990s. PMID:23679449

  3. Life-long shedding of Puumala hantavirus in wild bank voles (Myodes glareolus).

    PubMed

    Voutilainen, Liina; Sironen, Tarja; Tonteri, Elina; Bäck, Anne Tuiskunen; Razzauti, Maria; Karlsson, Malin; Wahlström, Maria; Niemimaa, Jukka; Henttonen, Heikki; Lundkvist, Åke

    2015-06-01

    The knowledge of viral shedding patterns and viraemia in the reservoir host species is a key factor in assessing the human risk of zoonotic viruses. The shedding of hantaviruses (family Bunyaviridae) by their host rodents has widely been studied experimentally, but rarely in natural settings. Here we present the dynamics of Puumala hantavirus (PUUV) shedding and viraemia in naturally infected wild bank voles (Myodes glareolus). In a monthly capture-mark-recapture study, we analysed 18 bank voles for the presence and relative quantity of PUUV RNA in the excreta and blood from 2 months before up to 8 months after seroconversion. The proportion of animals shedding PUUV RNA in saliva, urine and faeces peaked during the first month after seroconversion, but continued throughout the study period with only a slight decline. The quantity of shed PUUV in reverse transcription quantitative PCR (RT-qPCR) positive excreta was constant over time. In blood, PUUV RNA was present for up to 7 months but both the probability of viraemia and the virus load declined with time. Our findings contradict the current view of a decline in virus shedding after the acute phase and a short viraemic period in hantavirus infection - an assumption widely adopted in current epidemiological models. We suggest the life-long shedding as a means of hantaviruses to survive over host population bottlenecks, and to disperse in fragmented habitats where local host and/or virus populations face temporary extinctions. Our results indicate that the kinetics of pathogens in wild hosts may differ considerably from those observed in laboratory settings. PMID:25701819

  4. Co-circulation of Soricid- and Talpid-borne Hantaviruses in Poland

    PubMed Central

    Gu, Se Hun; Hejduk, Janusz; Markowski, Janusz; Kang, Hae Ji; Markowski, Marcin; Połatyńska, Małgorzata; Sikorska, Beata; Liberski, Paweł P.; Yanagihara, Richard

    2014-01-01

    Previously, we reported the discovery of a genetically distinct hantavirus, designated Boginia virus (BOGV), in the Eurasian water shrew (Neomys fodiens), as well as the detection of Seewis virus (SWSV) in the Eurasian common shrew (Sorex araneus), in central Poland. In this expanded study of 133 shrews and 69 moles captured during 2010–2013 in central and southeastern Poland, we demonstrate the co-circulation of BOGV in the Eurasian water shrew and SWSV in the Eurasian common shrew, Eurasian pygmy shrew (Sorex minutus) and Mediterranean water shrew (Neomys anomalus). In addition, we found high prevalence of Nova virus (NVAV) infection in the European mole (Talpa europaea), with evidence of NVAV RNA in heart, lung, liver, kidney, spleen and intestine. The nucleotide and amino acid sequence variation of the L segment among the SWSV strains was 0–18.8% and 0–5.4%, respectively. And for the 38 NVAV strains from European moles captured in Huta Dłutowska, the L-segment genetic similarity ranged from 94.1–100% at the nucleotide level and 96.3–100% at the amino acid level. Phylogenetic analyses showed geographic-specific lineages of SWSV and NVAV in Poland, not unlike that of rodent-borne hantaviruses, suggesting long-standing host-specific adaptation. The co-circulation and distribution of BOGV, SWSV and NVAV in Poland parallels findings of multiple hantavirus species coexisting in their respective rodent reservoir species elsewhere in Europe. Also, the detection of SWSV in three syntopic shrew species resembles spill over events observed among some rodent-borne hantaviruses. PMID:25445646

  5. Pathophysiology of a severe case of Puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant.

    PubMed

    Vaheri, Antti; Strandin, Tomas; Jääskeläinen, Anne J; Vapalahti, Olli; Jarva, Hanna; Lokki, Marja-Liisa; Antonen, Jaakko; Leppänen, Ilona; Mäkelä, Satu; Meri, Seppo; Mustonen, Jukka

    2014-11-01

    We recently described a patient with very severe Puumala hantavirus infection manifested by capillary leakage syndrome and shock. He was successfully treated with the bradykinin receptor antagonist, icatibant (Antonen et al., 2013). Here we report analysis of the pathophysiology which indicated pronounced complement activation, prolonged leukocytosis, extensive fibrinolysis, circulating histones, and defects in liver function. The patient had an uncommon HLA-phenotype, which may have contributed to the severe course of the disease. PMID:25194993

  6. A multistage differential transformation method for approximate solution of Hantavirus infection model

    NASA Astrophysics Data System (ADS)

    Gökdoğan, Ahmet; Merdan, Mehmet; Yildirim, Ahmet

    2012-01-01

    The goal of this study is presented a reliable algorithm based on the standard differential transformation method (DTM), which is called the multi-stage differential transformation method (MsDTM) for solving Hantavirus infection model. The results obtanied by using MsDTM are compared to those obtained by using the Runge-Kutta method (R-K-method). The proposed technique is a hopeful tool to solving for a long time intervals in this kind of systems.

  7. Person-to-Person Household and Nosocomial Transmission of Andes Hantavirus, Southern Chile, 2011

    PubMed Central

    Martinez-Valdebenito, Constanza; Calvo, Mario; Vial, Cecilia; Mansilla, Rita; Marco, Claudia; Palma, R. Eduardo; Vial, Pablo A.; Valdivieso, Francisca; Mertz, Gregory

    2014-01-01

    Andes hantavirus (ANDV) causes hantavirus cardiopulmonary syndrome in Chile and is the only hantavirus for which person-to-person transmission has been proven. We describe an outbreak of 5 human cases of ANDV infection in which symptoms developed in 2 household contacts and 2 health care workers after exposure to the index case-patient. Results of an epidemiologic investigation and sequence analysis of the virus isolates support person-to-person transmission of ANDV for the 4 secondary case-patients, including nosocomial transmission for the 2 health care workers. Health care personnel who have direct contact with ANDV case-patients or their body fluids should take precautions to prevent transmission of the virus. In addition, because the incubation period of ANDV after environmental exposure is longer than that for person-to-person exposure, all persons exposed to a confirmed ANDV case-patient or with possible environmental exposure to the virus should be monitored for 42 days for clinical symptoms. PMID:25272189

  8. Climate Variability and the Occurrence of Human Puumala Hantavirus Infections in Europe: A Systematic Review.

    PubMed

    Roda Gracia, J; Schumann, B; Seidler, A

    2015-09-01

    Hantaviruses are distributed worldwide and are transmitted by rodents. In Europe, the infection usually manifests as a mild form of haemorrhagic fever with renal syndrome (HFRS) known as nephropathia epidemica (NE), which is triggered by the virus species Puumala. Its host is the bank vole (Myodes glareolus). In the context of climate change, interest in the role of climatic factors for the disease has increased. A systematic review was conducted to investigate the association between climate variability and the occurrence of human Puumala hantavirus infections in Europe. We performed a literature search in the databases MEDLINE, EMBASE and Web of Science. Studies that investigated Puumala virus infection and climatic factors in any European country with a minimum collection period of 2 years were included. The selection of abstracts and the evaluation of included studies were performed by two independent reviewers. A total of 434 titles were identified in the databases, of which nine studies fulfilled the inclusion criteria. The majority of studies were conducted in central Europe (Belgium, France and Germany), while only two came from the north (Sweden) and one from the south (Bosnia). Strong evidence was found for a positive association between temperature and NE incidence in central Europe, while the evidence for northern Europe so far appears insufficient. Results regarding precipitation were contradictory. Overall, the complex relationships between climate and hantavirus infections need further exploration to identify specific health risks and initiate appropriate intervention measures in the context of climate change. PMID:25557350

  9. Selective predation on hantavirus-infected voles by owls and confounding effects from landscape properties.

    PubMed

    Khalil, Hussein; Ecke, Frauke; Evander, Magnus; Hörnfeldt, Birger

    2016-06-01

    It has been suggested that predators may protect human health through reducing disease-host densities or selectively preying on infected individuals from the population. However, this has not been tested empirically. We hypothesized that Tengmalm's owl (Aegolius funereus) selectively preys on hantavirus-infected individuals of its staple prey, the bank vole (Myodes glareolus). Bank voles are hosts of Puumala hantavirus, which causes a form of hemorrhagic fever in humans. Selective predation by owls on infected voles may reduce human disease risk. We compared the prevalence of anti-Puumala hantavirus antibodies (seroprevalence), in bank voles cached by owls in nest boxes to seroprevalence in voles trapped in closed-canopy forest around each nest box. We found no general difference in seroprevalence. Forest landscape structure could partly account for the observed patterns in seroprevalence. Only in more connected forest patches was seroprevalence in bank voles cached in nest boxes higher than seroprevalence in trapped voles. This effect disappeared with increasing forest patch isolation, as seroprevalence in trapped voles increased with forest patch isolation, but did not in cached voles. Our results suggest a complex relationship between zoonotic disease prevalence in hosts, their predators, and landscape structure. Some mechanisms that may have caused the seroprevalence patterns in our results include higher bank vole density in isolated forest patches. This study offers future research potential to shed further light on the contribution of predators and landscape properties to human health. PMID:26873607

  10. Multiplex Analysis of Serum Cytokines in Humans with Hantavirus Pulmonary Syndrome

    PubMed Central

    Morzunov, Sergey P.; Khaiboullina, Svetlana F.; St. Jeor, Stephen; Rizvanov, Albert A.; Lombardi, Vincent C.

    2015-01-01

    Hantavirus pulmonary syndrome (HPS) is an acute zoonotic disease transmitted primarily through inhalation of virus-contaminated aerosols. Hantavirus infection of endothelial cells leads to increased vascular permeability without a visible cytopathic effect. For this reason, it has been suggested that the pathogenesis of HPS is indirect with immune responses, such as cytokine production, playing a dominant role. In order to investigate their potential contribution to HPS pathogenesis, we analyzed the serum of hantavirus-infected subjects and healthy controls for 68 different cytokines, chemokines, angiogenic, and growth factors. Our analysis identified differential expression of cytokines that promote tissue migration of mononuclear cells including T lymphocytes, natural killer cells, and dendritic cells. Additionally, we observed a significant upregulation of cytokines known to regulate leukocyte migration and subsequent repair of lung tissue, as well as cytokines known to increase endothelial monolayer permeability and facilitate leukocyte transendothelial migration. Conversely, we observed a downregulation of cytokines associated with platelet numbers and function, consistent with the thrombocytopenia observed in subjects with HPS. This study corroborates clinical findings and extends our current knowledge regarding immunological and laboratory findings in subjects with HPS. PMID:26379668

  11. Multiplex Analysis of Serum Cytokines in Humans with Hantavirus Pulmonary Syndrome.

    PubMed

    Morzunov, Sergey P; Khaiboullina, Svetlana F; St Jeor, Stephen; Rizvanov, Albert A; Lombardi, Vincent C

    2015-01-01

    Hantavirus pulmonary syndrome (HPS) is an acute zoonotic disease transmitted primarily through inhalation of virus-contaminated aerosols. Hantavirus infection of endothelial cells leads to increased vascular permeability without a visible cytopathic effect. For this reason, it has been suggested that the pathogenesis of HPS is indirect with immune responses, such as cytokine production, playing a dominant role. In order to investigate their potential contribution to HPS pathogenesis, we analyzed the serum of hantavirus-infected subjects and healthy controls for 68 different cytokines, chemokines, angiogenic, and growth factors. Our analysis identified differential expression of cytokines that promote tissue migration of mononuclear cells including T lymphocytes, natural killer cells, and dendritic cells. Additionally, we observed a significant upregulation of cytokines known to regulate leukocyte migration and subsequent repair of lung tissue, as well as cytokines known to increase endothelial monolayer permeability and facilitate leukocyte transendothelial migration. Conversely, we observed a downregulation of cytokines associated with platelet numbers and function, consistent with the thrombocytopenia observed in subjects with HPS. This study corroborates clinical findings and extends our current knowledge regarding immunological and laboratory findings in subjects with HPS. PMID:26379668

  12. New York 1 and Sin Nombre Viruses Are Serotypically Distinct Viruses Associated with Hantavirus Pulmonary Syndrome

    PubMed Central

    Gavrilovskaya, Irina; LaMonica, Rachel; Fay, Mary-Ellen; Hjelle, Brian; Schmaljohn, Connie; Shaw, Robert; Mackow, Erich R.

    1999-01-01

    New York 1 virus (NY-1) and Sin Nombre virus (SN) are associated with hantavirus pulmonary syndrome (HPS). NY-1 and SN are derived from unique mammalian hosts and geographic locations but have similar G1 and G2 surface proteins (93 and 97% identical, respectively). Focus reduction neutralization assays were used to define the serotypic relationship between NY-1 and SN. Sera from NY-1-positive Peromyscus leucopus neutralized NY-1 and SN at titers of ≥1/3,200 and ≤1/400, respectively (n = 12). Conversely, SN-specific rodent sera neutralized NY-1 and SN at titers of <1/400 and 1/6,400, respectively (n = 13). Acute-phase serum from a New York HPS patient neutralized NY-1 (1/640) but not SN (<1/20), while sera from HPS patients from the southwestern United States had 4- to >16-fold-lower neutralizing titers to NY-1 than to SN. Reference sera to Hantaan, Seoul, and Prospect Hill viruses also failed to neutralize NY-1. These results indicate that SN and NY-1 define unique hantavirus serotypes and implicate the presence of additional HPS-associated hantavirus serotypes in the Americas. PMID:9854075

  13. A Habitat-Based Model for the Spread of Hantavirus Between Reservoir and Spillover Species

    PubMed Central

    Allen, Linda J. S.; Wesley, Curtis L.; Owen, Robert D.; Goodin, Douglas G.; Koch, David; Jonsson, Colleen B.; Chu, Yong-Kyu; Shawn Hutchinson, J. M.; Paige, Robert L.

    2009-01-01

    New habitat-based models for spread of hantavirus are developed which account for interspecies interaction. Existing habitat-based models do not consider interspecies pathogen transmission, a primary route for emergence of new infectious diseases and reservoirs in wildlife and man. The modeling of interspecies transmission has the potential to provide more accurate predictions of disease persistence and emergence dynamics. The new models are motivated by our recent work on hantavirus in rodent communities in Paraguay. Our Paraguayan data illustrate the spatial and temporal overlap among rodent species, one of which is the reservoir species for Jabora virus and others which are spillover species. Disease transmission occurs when their habitats overlap. Two mathematical models, a system of ordinary differential equations (ODE) and a continuous-time Markov chain (CTMC) model, are developed for spread of hantavirus between a reservoir and a spillover species. Analysis of a special case of the ODE model provides an explicit expression for the basic reproduction number, ℛ0, such that if ℛ0 < 1, then the pathogen does not persist in either population but if ℛ0 > 1, pathogen outbreaks or persistence may occur. Numerical simulations of the CTMC model display sporadic disease incidence, a new behavior of our habitat-based model, not present in other models, but which is a prominent feature of the seroprevalence data from Paraguay. Environmental changes that result in greater habitat overlap result in more encounters among various species that may lead to pathogen outbreaks and pathogen establishment in a new host. PMID:19616014

  14. Laguna Negra Virus Infection Causes Hantavirus Pulmonary Syndrome in Turkish Hamsters (Mesocricetus brandti).

    PubMed

    Hardcastle, K; Scott, D; Safronetz, D; Brining, D L; Ebihara, H; Feldmann, H; LaCasse, R A

    2016-01-01

    Laguna Negra virus (LNV) is a New World hantavirus associated with severe and often fatal cardiopulmonary disease in humans, known as hantavirus pulmonary syndrome (HPS). Five hamster species were evaluated for clinical and serologic responses following inoculation with 4 hantaviruses. Of the 5 hamster species, only Turkish hamsters infected with LNV demonstrated signs consistent with HPS and a fatality rate of 43%. Clinical manifestations in infected animals that succumbed to disease included severe and rapid onset of dyspnea, weight loss, leukopenia, and reduced thrombocyte numbers as compared to uninfected controls. Histopathologic examination revealed lung lesions that resemble the hallmarks of HPS in humans, including interstitial pneumonia and pulmonary edema, as well as generalized infection of endothelial cells and macrophages in major organ tissues. Histologic lesions corresponded to the presence of viral antigen in affected tissues. To date, there have been no small animal models available to study LNV infection and pathogenesis. The Turkish hamster model of LNV infection may be important in the study of LNV-induced HPS pathogenesis and development of disease treatment and prevention strategies. PMID:25722219

  15. Maripa Hantavirus in French Guiana: Phylogenetic Position and Predicted Spatial Distribution of Rodent Hosts

    PubMed Central

    de Thoisy, Benoît; Matheus, Séverine; Catzeflis, François; Clément, Luc; Barrioz, Sébastien; Guidez, Amandine; Donato, Damien; Cornu, Jean-François; Brunaux, Olivier; Guitet, Stéphane; Lacoste, Vincent; Lavergne, Anne

    2014-01-01

    A molecular screening of wild-caught rodents was conducted in French Guiana, South America to identify hosts of the hantavirus Maripa described in 2008 in a hantavirus pulmonary syndrome (HPS) case. Over a 9-year period, 418 echimyids and murids were captured. Viral RNA was detected in two sigmodontine rodents, Oligoryzomys fulvescens and Zygodontomys brevicauda, trapped close to the house of a second HPS case that occurred in 2009 and an O. fulvescens close to the fourth HPS case identified in 2013. Sequences from the rodents had 96% and 97% nucleotide identity (fragment of S and M segments, respectively) with the sequence of the first human HPS case. Phylogenetic reconstructions based on the complete sequence of the S segment show that Maripa virus is closely related to Rio Mamore hantavirus. Using environmental descriptors of trapping sites, including vegetation, landscape units, rain, and human disturbance, a maximal entropy-based species distribution model allowed for identification of areas of higher predicted occurrence of the two rodents, where emergence risks of Maripa virus are expected to be higher. PMID:24752689

  16. Human puumala and dobrava hantavirus infections in the Black Sea region of Turkey: a cross-sectional study.

    PubMed

    Gozalan, Aysegul; Kalaycioglu, Handan; Uyar, Yavuz; Sevindi, Demet Furkan; Turkyilmaz, Bedia; Çakir, Vedat; Cindemir, Cengiz; Unal, Belgin; Yağçi-Çağlayik, Dilek; Korukluoglu, Gulay; Ertek, Mustafa; Heyman, Paul; Lundkvist, Åke

    2013-02-01

    This study was carried out to better understand the epidemiology of hantaviruses in a province of Turkey (Giresun) where human hantavirus disease has recently been detected. In this cross-sectional study, a total of 626 blood samples from healthy people aged 15 and 84 years old were collected both in urban and rural areas in 2009. The sera were tested by enzyme-linked immunosorbent assay (ELISA), immunoblotting assay, and the focus reduction neutralization test (FRNT). We screened the samples by an ELISA and found that 65/626 samples reacted positively for the presence of hantavirus-reactive immunoglobulin G (IgG). Twenty of the 65 ELISA-positive samples could be confirmed by an immunobloting assay, and the overall seroprevalence was thereby calculated to 3.2% (20/626). The seroprevalence of the people living in wood areas or adobe houses 9/17 (52.9%) was significantly higher than among people living in concrete houses 10/47 (21.3%) (p=0.014). Finally, 3 of the 20 immunoblot-positive sera were confirmed as specific for the Puumala hantavirus serotype by FRNT, 1 serum was confirmed as Dobrava virus-specific, whereas 1 serum was found to be equally reactive to Dobrava and Saaremaa viruses. We will now focus on further investigations of the ecology and epidemiology of hantaviruses in humans and their carrier animals in Turkey, studies that have already been started and will be further intensified. PMID:23289396

  17. Isolation and partial characterization of a highly divergent lineage of hantavirus from the European mole (Talpa europaea).

    PubMed

    Gu, Se Hun; Kumar, Mukesh; Sikorska, Beata; Hejduk, Janusz; Markowski, Janusz; Markowski, Marcin; Liberski, Paweł P; Yanagihara, Richard

    2016-01-01

    Genetically distinct hantaviruses have been identified in five species of fossorial moles (order Eulipotyphla, family Talpidae) from Eurasia and North America. Here, we report the isolation and partial characterization of a highly divergent hantavirus, named Nova virus (NVAV), from lung tissue of a European mole (Talpa europaea), captured in central Poland in August 2013. Typical hantavirus-like particles, measuring 80-120 nm in diameter, were found in NVAV-infected Vero E6 cells by transmission electron microscopy. Whole-genome sequences of the isolate, designated NVAV strain Te34, were identical to that amplified from the original lung tissue, and phylogenetic analysis of the full-length L, M and S segments, using maximum-likelihood and Bayesian methods, showed that NVAV was most closely related to hantaviruses harbored by insectivorous bats, consistent with an ancient evolutionary origin. Infant Swiss Webster mice, inoculated with NVAV by the intraperitoneal route, developed weight loss and hyperactivity, beginning at 16 days, followed by hind-limb paralysis and death. High NVAV RNA copies were detected in lung, liver, kidney, spleen and brain by quantitative real-time RT-PCR. Neuropathological examination showed astrocytic and microglial activation and neuronal loss. The first mole-borne hantavirus isolate will facilitate long-overdue studies on its infectivity and pathogenic potential in humans. PMID:26892544

  18. Molecular phylogeny of hantaviruses harbored by insectivorous bats in Côte d'Ivoire and Vietnam.

    PubMed

    Gu, Se Hun; Lim, Burton K; Kadjo, Blaise; Arai, Satoru; Kim, Jeong-Ah; Nicolas, Violaine; Lalis, Aude; Denys, Christiane; Cook, Joseph A; Dominguez, Samuel R; Holmes, Kathryn V; Urushadze, Lela; Sidamonidze, Ketevan; Putkaradze, Davit; Kuzmin, Ivan V; Kosoy, Michael Y; Song, Jin-Won; Yanagihara, Richard

    2014-05-01

    The recent discovery of genetically distinct hantaviruses in multiple species of shrews and moles prompted a further exploration of their host diversification by analyzing frozen, ethanol-fixed and RNAlater®-preserved archival tissues and fecal samples from 533 bats (representing seven families, 28 genera and 53 species in the order Chiroptera), captured in Asia, Africa and the Americas in 1981-2012, using RT-PCR. Hantavirus RNA was detected in Pomona roundleaf bats (Hipposideros pomona) (family Hipposideridae), captured in Vietnam in 1997 and 1999, and in banana pipistrelles (Neoromicia nanus) (family Vespertilionidae), captured in Côte d'Ivoire in 2011. Phylogenetic analysis, based on the full-length S- and partial M- and L-segment sequences using maximum likelihood and Bayesian methods, demonstrated that the newfound hantaviruses formed highly divergent lineages, comprising other recently recognized bat-borne hantaviruses in Sierra Leone and China. The detection of bat-associated hantaviruses opens a new era in hantavirology and provides insights into their evolutionary origins. PMID:24784569

  19. Responses of small mammals to habitat fragmentation: epidemiological considerations for rodent-borne hantaviruses in the Americas.

    PubMed

    Rubio, André V; Ávila-Flores, Rafael; Suzán, Gerardo

    2014-12-01

    Rodent-borne hantaviruses are a group of zoonotic agents that cause hemorrhagic fever in humans. The transmission of hantaviruses among rodent hosts may be higher with the increase of reservoir host abundance in a given area (density-dependent transmission) and with the decrease of small mammal diversity (dilution effect phenomenon). These population and community parameters may be modified by habitat fragmentation; however, studies that focus on fragmentation and its effect on hantavirus infection risk are scarce. To further understanding of this issue, we assessed some population and community responses of rodents that may increase the risk for hantavirus transmission among wildlife hosts in the Americas. We conducted a meta-analysis of published studies to assess the responses of small mammals to fragmentation of native habitats, relative to patch size. Our analyses included five countries and 14 case studies for abundance of reservoir hosts (8 species) and 15 case studies for species richness. We found that a reduction of patch area due to habitat fragmentation is associated with increased reservoir host abundances and decreased small mammal richness, which is mainly due to the loss of non-host small mammals. According to these results, habitat fragmentation in the Americas should be considered as an epidemiological risk factor for hantavirus transmission to humans. These findings are important to assess potential risk of infection when fragmentation of native habitats occurs. PMID:24845575

  20. Isolation and partial characterization of a highly divergent lineage of hantavirus from the European mole (Talpa europaea)

    PubMed Central

    Gu, Se Hun; Kumar, Mukesh; Sikorska, Beata; Hejduk, Janusz; Markowski, Janusz; Markowski, Marcin; Liberski, Paweł P.; Yanagihara, Richard

    2016-01-01

    Genetically distinct hantaviruses have been identified in five species of fossorial moles (order Eulipotyphla, family Talpidae) from Eurasia and North America. Here, we report the isolation and partial characterization of a highly divergent hantavirus, named Nova virus (NVAV), from lung tissue of a European mole (Talpa europaea), captured in central Poland in August 2013. Typical hantavirus-like particles, measuring 80–120 nm in diameter, were found in NVAV-infected Vero E6 cells by transmission electron microscopy. Whole-genome sequences of the isolate, designated NVAV strain Te34, were identical to that amplified from the original lung tissue, and phylogenetic analysis of the full-length L, M and S segments, using maximum-likelihood and Bayesian methods, showed that NVAV was most closely related to hantaviruses harbored by insectivorous bats, consistent with an ancient evolutionary origin. Infant Swiss Webster mice, inoculated with NVAV by the intraperitoneal route, developed weight loss and hyperactivity, beginning at 16 days, followed by hind-limb paralysis and death. High NVAV RNA copies were detected in lung, liver, kidney, spleen and brain by quantitative real-time RT-PCR. Neuropathological examination showed astrocytic and microglial activation and neuronal loss. The first mole-borne hantavirus isolate will facilitate long-overdue studies on its infectivity and pathogenic potential in humans. PMID:26892544

  1. DIABETES MELLITUS COMO FACTOR DE RIESGO DE DEMENCIA EN LA POBLACIÓN ADULTA MAYOR MEXICANA

    PubMed Central

    Silvia, Mejía-Arango; Clemente, y Zúñiga-Gil

    2012-01-01

    Introduccion La diabetes mellitus y las demencias constituyen dos problemas crecientes de salud entre la población adulta mayor del mundo y en particular de los paises en desarrollo. Hacen falta estudios longitudinales sobre el papel de la diabetes como factor de riesgo para demencia. Objetivo Determinar el riesgo de demencia en sujetos Mexicanos con diabetes mellitus tipo 2. Materiales y Metodos Los sujetos diabéticos libres de demencia pertenecientes al Estudio Nacional de Salud y Envejecimiento en México fueron evaluados a los dos años de la línea de base. Se estudió el papel de los factores sociodemográficos, de otras comorbilidades y del tipo de tratamiento en la conversión a demencia. Resultados Durante la línea de base 749 sujetos (13.8%) tuvieron diabetes. El riesgo de desarrollar demencia en estos individuos fue el doble (RR, 2.08 IC 95%, 1.59–2.73). Se encontró un riesgo mayor en individuos de 80 años y más (RR 2.44 IC 95%, 1.46–4.08), en los hombres (RR, 2.25 IC 95%, 1.46–3.49) y en sujetos con nivel educativo menor de 7 años. El estar bajo tratamiento con insulina incrementó el riesgo de demencia (RR, 2.83, IC 95%, 1.58–5.06). Las otras comorbilidades que aumentaron el riesgo de demencia en los pacientes diabéticos fueron la hipertensión (RR, 2.75, IC 95%, 1.86–4.06) y la depresión (RR, 3.78, 95% IC 2.37–6.04). Conclusión Los sujetos con diabetes mellitus tienen un riesgo mayor de desarrollar demencia, La baja escolaridad y otras comorbilidades altamente prevalentes en la población Mexicana contribuyen a la asociación diabetes-demencia. PMID:21948010

  2. [The epizootological and virological characteristics of a natural hantavirus infection focus in the subtropic zone of the Krasnodarsk Territory].

    PubMed

    Tkachenko, E A; Okulova, N M; Iunicheva, Iu V; Morzunov, S P; Khaĭbulina, S F; Riabova, T E; Vasilenko, L E; Bashkirtsev, V N; Dzagurova, T K; Gorbachkova, E A; Sedova, N S; Balakirev, A E; Dekonenko, A E; Drozdov, S G

    2005-01-01

    A natural focus of hantavirus infection was detected and examined during the studies conducted in 2000-2002 around the Sochi (the western spurs of the Great Caucasus Ridge, which descended to the Black Sea (the Krasnodar Territory of Russia). At least 4 rodent species, such as Microtus majori, A. (S.) ponticus, A. agrarius, A. (S.) ciscaucasicus, were shown to participate in the circulation of hantaviruses. A comparative analysis of the nucleotide sequences of genomic S- and M-segments of hantaviruses has provided evidence that 13 viral RNA isolates from the A. (S.) ciscaucasicus belong to the Dobrava/Belgrade virus clade; however the RNA isolate from the Microtus majori belong to the Tula virus clade. PMID:16078428

  3. Using Geographic Information System-based Ecologic Niche Models to Forecast the Risk of Hantavirus Infection in Shandong Province, China

    PubMed Central

    Wei, Lan; Qian, Quan; Wang, Zhi-Qiang; Glass, Gregory E.; Song, Shao-Xia; Zhang, Wen-Yi; Li, Xiu-Jun; Yang, Hong; Wang, Xian-Jun; Fang, Li-Qun; Cao, Wu-Chun

    2011-01-01

    Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in Shandong Province, China. In this study, we combined ecologic niche modeling with geographic information systems (GIS) and remote sensing techniques to identify the risk factors and affected areas of hantavirus infections in rodent hosts. Land cover and elevation were found to be closely associated with the presence of hantavirus-infected rodent hosts. The averaged area under the receiver operating characteristic curve was 0.864, implying good performance. The predicted risk maps based on the model were validated both by the hantavirus-infected rodents' distribution and HFRS human case localities with a good fit. These findings have the applications for targeting control and prevention efforts. PMID:21363991

  4. Microvascular inflammation and acute tubular necrosis are major histologic features of hantavirus nephropathy.

    PubMed

    Gnemmi, Viviane; Verine, Jérôme; Vrigneaud, Laurence; Glowacki, François; Ratsimbazafy, Anderson; Copin, Marie-Christine; Dewilde, Anny; Buob, David

    2015-06-01

    Hantavirus nephropathy (HVN) is an uncommon etiology of acute renal failure due to hantavirus infection. Pathological features suggestive of HVN historically reported are medullary interstitial hemorrhages in a background of acute interstitial nephritis (AIN). However, interstitial hemorrhages may be lacking because of medullary sampling error. This emphasizes that other pathological criteria may be of interest. We performed a retrospective clinicopathological study of 17 serologically proven HVN cases with renal biopsy from 2 nephrology centers in northern France. Histologic analysis was completed by immunohistochemistry with anti-CD3, anti-CD68, and anti-CD34 antibodies. Three control groups were not related to hantavirus infection: acute tubular necrosis (ATN) of ischemic or toxic etiology and AIN were used for comparison. Renal biopsy analysis showed that almost all HVN cases with medullary sampling (9/10) displayed interstitial hemorrhages, whereas focal hemorrhages were detected in 2 of the 7 "cortex-only" specimens. ATN was common, as it was present in 15 (88.2%) of 17 HVN cases. By contrast, interstitial inflammation was scarce with no inflammation or only slight inflammation, representing 15 (88.2%) of 17 cases. Moreover, HVN showed inflammation of renal microvessels with cortical peritubular capillaritis and medullary vasa recta inflammation; peritubular capillaritis was significantly higher in HVN after comparison with ischemic and toxic ATN controls (P = .0001 and P = .003, respectively), but not with AIN controls. Immunohistochemical studies highlighted the involvement of T cells and macrophages in renal microvascular inflammation related to HVN. Our study showed that microvascular inflammation, especially cortical peritubular capillaritis, and ATN are important histologic features of HVN. PMID:25791582

  5. Hantavirus reservoir Oligoryzomys longicaudatus spatial distribution sensitivity to climate change scenarios in Argentine Patagonia

    PubMed Central

    Carbajo, Aníbal E; Vera, Carolina; González, Paula LM

    2009-01-01

    Background Oligoryzomys longicaudatus (colilargo) is the rodent responsible for hantavirus pulmonary syndrome (HPS) in Argentine Patagonia. In past decades (1967–1998), trends of precipitation reduction and surface air temperature increase have been observed in western Patagonia. We explore how the potential distribution of the hantavirus reservoir would change under different climate change scenarios based on the observed trends. Methods Four scenarios of potential climate change were constructed using temperature and precipitation changes observed in Argentine Patagonia between 1967 and 1998: Scenario 1 assumed no change in precipitation but a temperature trend as observed; scenario 2 assumed no changes in temperature but a precipitation trend as observed; Scenario 3 included changes in both temperature and precipitation trends as observed; Scenario 4 assumed changes in both temperature and precipitation trends as observed but doubled. We used a validated spatial distribution model of O. longicaudatus as a function of temperature and precipitation. From the model probability of the rodent presence was calculated for each scenario. Results If changes in precipitation follow previous trends, the probability of the colilargo presence would fall in the HPS transmission zone of northern Patagonia. If temperature and precipitation trends remain at current levels for 60 years or double in the future 30 years, the probability of the rodent presence and the associated total area of potential distribution would diminish throughout Patagonia; the areas of potential distribution for colilargos would shift eastwards. These results suggest that future changes in Patagonia climate may lower transmission risk through a reduction in the potential distribution of the rodent reservoir. Conclusion According to our model the rates of temperature and precipitation changes observed between 1967 and 1998 may produce significant changes in the rodent distribution in an equivalent

  6. Hantavirus testing in rodents of north-central New Mexico 1993-1995

    SciTech Connect

    Biggs, J.; Bennett, K.; Salisbury, M.

    1996-03-01

    In 1993, an outbreak of a new strain of hantavirus in the southwestern US indicated that deer mice (Peromyscus maniculatus) was the primary carrier of the virus. In 1993, 1994, and 1995 the Ecological Studies Team (EST) at Los Alamos National Laboratory surveyed small mammal populations using live capture-recapture methods in Los Alamos County, New Mexico, to determine seroprevalence of hantavirus in this region. EST used trapping grids in 1993 and 1994 and used trapping webs in 1995. Grids were 120 m x 120 m (400 ft x 400 ft) with 144 trap stations at each grid. Three webs consisting of 148 traps each were used in 1995. Trapping took place over 4 to 8 consecutive nights. Programs CAPTURE and Distance were used to determine density estimates for grids and webs, respectively. Blood samples were analyzed in 1993 by the Centers for Disease Control and the University of New Mexico, School of Medicine. The 1994 and 1995 samples were analyzed by the University of New Mexico, School of Medicine. The deer mouse (Peromyscus maniculatus) was the most commonly captured species at all locations except one site where voles (Microtus spp.) were the most commonly captured species. Other species sampled included: harvest mice (Reithrodontomys megalotis), woodrats (Neotoma spp.), shrews (Sorex spp.), white-footed mice (Peromyscus leucopus), pinyon mice (Peromyscus trueii), and brush mouse (Peromyscus boylii). Results of the 1993, 1994, and 1995 testing identified a total overall seroprevalence rate among deer mice of approximately 5.5%, 4.2%, and 0%, respectively. Several other species tested positive for the hantavirus but it is uncertain if it is Sin Nombre virus. Further studies will be necessary to quantify seroprevalence rates in those species. Higher seroprevalence rates were found in males than females. Seroprevalence rates for Los Alamos County were much lower than elsewhere in the region.

  7. Simulations in the mathematical modeling of the spread of the Hantavirus

    NASA Astrophysics Data System (ADS)

    Aguirre, M. A.; Abramson, G.; Bishop, A. R.; Kenkre, V. M.

    2002-10-01

    The range of validity of a recently proposed deterministic (mean field) model of the spread of the Hantavirus infection is studied with the help of Monte Carlo simulations for the evolution of mice populations. The simulation is found to reproduce earlier results on the average but to display additional behavior stemming from discreteness in mice number and from fluctuations of the finite size system. It is shown that mice diffusion affects those additional features of the simulation in a physically understandable manner, higher diffusion constants leading to greater agreement with the mean field results.

  8. Effects of seasonality and of internal fluctuations on the spreading of Hantavirus

    NASA Astrophysics Data System (ADS)

    Lindenberg, Katja; Escudero, Carlos; Buceta, Javier; de la Rubia, Francisco J.

    2004-05-01

    We present an analysis of two features that generalize the original model for the spread of the Hantavirus introduced by Abramson and Kenkre [Phys. Rev. E Vol. 66, 011912 (2002)]. One, the effect of seasonal alternations, may cause the virus to spread under conditions that do not lead to an epidemic under the action of either season alone. The other, the effect of internal fluctuations, modifies the distribution of infected mice and may lead to extinction of the infected population even when the mean population is above epidemic conditions.

  9. DUCHAS VAGINALES Y OTROS RIESGOS DE VAGINOSIS BACTERIANA

    PubMed Central

    Chávez, Natividad; Molina, Helfer; Sánchez, Jorge; Gelaye, Bizu; Sánchez, Sixto E.

    2010-01-01

    Vaginosis bacteriana (VB) es una infección caracterizada por el cambio en la microflora de la vagina, asociándose a resultados adversos del embarazo y a la adquisición de infecciones de transmisión sexual (ITS), incluyendo el VIH. En este estudio se buscó la asociación entre el uso de duchas vaginales y otros factores de riesgos con VB. Se usó un diseño observacional descriptivo transversal prospectivo, en 1,252 mujeres que asistieron al servicio de planificación familiar de tres hospitales nacionales (Dos de Mayo, Arzobispo Loayza, San Bartolomé) y el Instituto Materno Perinatal, durante el año 1997. Se utilizó un cuestionario estructurado donde se registraron variables socio demográficas y características del estilo de vida de las participantes. VB fue diagnosticada mediante el puntaje de Nugent. Se empleó análisis de regresión logística para calcular odds ratio (OR) e intervalos de confianza al 95%. La edad promedio de las participantes fue 25.1 ± 4,7 años, el 23.4% tenían más de 11 años de educación. La prevalencía de VB fue 20,1%. Las mujeres que practicaban duchas vaginales tuvieron 2.28 veces (OR = 2.28, IC 95% [1.0–5.0]) mayor probabilidad de tener VB comparado con aquellas que no lo practicaban. Tener dos o más parejas sexuales estuvo asociado con 2.0 veces (OR =2.0, IC 95% [1.2–3.5]) mayor probabilidad de adquirir VB comparado con aquellas que habían tenido solo una pareja sexual. Las participantes que iniciaron una relación sexual a una edad temprana tuvieron 1.4 veces (OR=1.4, IC 95% [1.0 –1.9]) mayor probabilidad de adquirir VB. El uso de duchas vaginales es un factor de riesgo de VB. Los programas destinados a la salud de la mujer deben abordar las repercusiones perjudiciales para la salud asociados con las duchas vaginales. PMID:21132048

  10. Serological evidence of hantavirus infection in apparently healthy people from rural and slum communities in southern Chile.

    PubMed

    Muñoz-Zanzi, Claudia; Saavedra, Farides; Otth, Carola; Domancich, Ljubica; Hott, Melissa; Padula, Paula

    2015-04-01

    Hantavirus disease in America has been recognizable because of its rapid progression in clinical cases, occurrence in previously healthy young adults, and high case fatality rate. Hantavirus disease has been proposed now to define the diversity of clinical manifestations. Since 1995, a total of 902 cases of hantavirus pulmonary syndrome have been reported in Chile, caused by Andes virus (ANDV), with overall fatality of 32%. This report describes the sero-epidemiology of hantavirus in apparently healthy people in rural and urban slum communities from southern Chile. Ten of 934 samples yielded a positive result resulting in a seroprevalence of 1.07% (95% confidence intervals: 0.05%-2.0%). A higher proportion of positive samples was found among individuals from rural villages (1.3%) and slums (1.5%) compared with farms (0.5%). Seropositivity was associated with age (p = 0.011), low education level (p = 0.006) and occupations linked to the household (homemaker, retired, or student) (p = 0.016). No evidence of infection was found in 38 sigmodontinae rodents trapped in the peri-domestic environment. Our findings highlight that exposure risk was associated with less documented risk factors, such as women in slum and rural villages, and the occurrence of infection that may have presented as flu-like illness that did not require medical attention or was misdiagnosed. PMID:25912713

  11. Serological Evidence of Hantavirus Infection in Apparently Healthy People from Rural and Slum Communities in Southern Chile

    PubMed Central

    Muñoz-Zanzi, Claudia; Saavedra, Farides; Otth, Carola; Domancich, Ljubica; Hott, Melissa; Padula, Paula

    2015-01-01

    Hantavirus disease in America has been recognizable because of its rapid progression in clinical cases, occurrence in previously healthy young adults, and high case fatality rate. Hantavirus disease has been proposed now to define the diversity of clinical manifestations. Since 1995, a total of 902 cases of hantavirus pulmonary syndrome have been reported in Chile, caused by Andes virus (ANDV), with overall fatality of 32%. This report describes the sero-epidemiology of hantavirus in apparently healthy people in rural and urban slum communities from southern Chile. Ten of 934 samples yielded a positive result resulting in a seroprevalence of 1.07% (95% confidence intervals: 0.05%–2.0%). A higher proportion of positive samples was found among individuals from rural villages (1.3%) and slums (1.5%) compared with farms (0.5%). Seropositivity was associated with age (p = 0.011), low education level (p = 0.006) and occupations linked to the household (homemaker, retired, or student) (p = 0.016). No evidence of infection was found in 38 sigmodontinae rodents trapped in the peri-domestic environment. Our findings highlight that exposure risk was associated with less documented risk factors, such as women in slum and rural villages, and the occurrence of infection that may have presented as flu-like illness that did not require medical attention or was misdiagnosed. PMID:25912713

  12. Genetic variants of Cao Bang hantavirus in the Chinese mole shrew (Anourosorex squamipes) and Taiwanese mole shrew (Anourosorex yamashinai).

    PubMed

    Gu, Se Hun; Arai, Satoru; Yu, Hon-Tsen; Lim, Burton K; Kang, Hae Ji; Yanagihara, Richard

    2016-06-01

    To determine the genetic diversity and geographic distribution of Cao Bang virus (CBNV) and to ascertain the existence of CBNV-related hantaviruses, natural history collections of archival tissues from Chinese mole shrews (Anourosorex squamipes) and Taiwanese mole shrews (Anourosorex yamashinai), captured in Guizho Province, People's Republic of China, and in Nantou County, Taiwan, in 2006 and 1989, respectively, were analyzed for hantavirus RNA by RT-PCR. Pair-wise alignment and comparison of the S-, M- and L-segment sequences indicated CBNV in two of five Chinese mole shrews and a previously unrecognized hantavirus, named Xinyi virus (XYIV), in seven of 15 Taiwanese mole shrews. XYIV was closely related to CBNV in Vietnam and China, as well as to Lianghe virus (LHEV), recently reported as a distinct hantavirus species in Chinese mole shrews from Yunnan Province in China. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that XYIV shared a common ancestry with CBNV and LHEV, in keeping with the evolutionary relationship between Anourosorex mole shrews. Until such time that tissue culture isolates of CBNV, LHEV and XYIV can be fully analyzed, XYIV and LHEV should be regarded as genetic variants, or genotypes, of CBNV. PMID:26921799

  13. More Novel Hantaviruses and Diversifying Reservoir Hosts — Time for Development of Reservoir-Derived Cell Culture Models?

    PubMed Central

    Eckerle, Isabella; Lenk, Matthias; Ulrich, Rainer G.

    2014-01-01

    Due to novel, improved and high-throughput detection methods, there is a plethora of newly identified viruses within the genus Hantavirus. Furthermore, reservoir host species are increasingly recognized besides representatives of the order Rodentia, now including members of the mammalian orders Soricomorpha/Eulipotyphla and Chiroptera. Despite the great interest created by emerging zoonotic viruses, there is still a gross lack of in vitro models, which reflect the exclusive host adaptation of most zoonotic viruses. The usually narrow host range and genetic diversity of hantaviruses make them an exciting candidate for studying virus-host interactions on a cellular level. To do so, well-characterized reservoir cell lines covering a wide range of bat, insectivore and rodent species are essential. Most currently available cell culture models display a heterologous virus-host relationship and are therefore only of limited value. Here, we review the recently established approaches to generate reservoir-derived cell culture models for the in vitro study of virus-host interactions. These successfully used model systems almost exclusively originate from bats and bat-borne viruses other than hantaviruses. Therefore we propose a parallel approach for research on rodent- and insectivore-borne hantaviruses, taking the generation of novel rodent and insectivore cell lines from wildlife species into account. These cell lines would be also valuable for studies on further rodent-borne viruses, such as orthopox- and arenaviruses. PMID:24576845

  14. A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS).

    PubMed

    Hooper, Jay W; Josleyn, Matthew; Ballantyne, John; Brocato, Rebecca

    2013-09-13

    Sin Nombre virus (SNV; family Bunyaviridae, genus Hantavirus) causes a hemorrhagic fever known as hantavirus pulmonary syndrome (HPS) in North America. There have been approximately 200 fatal cases of HPS in the United States since 1993, predominantly in healthy working-age males (case fatality rate 35%). There are no FDA-approved vaccines or drugs to prevent or treat HPS. Previously, we reported that hantavirus vaccines based on the full-length M gene segment of Andes virus (ANDV) for HPS in South America, and Hantaan virus (HTNV) and Puumala virus (PUUV) for hemorrhagic fever with renal syndrome (HFRS) in Eurasia, all elicited high-titer neutralizing antibodies in animal models. HFRS is more prevalent than HPS (>20,000 cases per year) but less pathogenic (case fatality rate 1-15%). Here, we report the construction and testing of a SNV full-length M gene-based DNA vaccine to prevent HPS. Rabbits vaccinated with the SNV DNA vaccine by muscle electroporation (mEP) developed high titers of neutralizing antibodies. Furthermore, hamsters vaccinated three times with the SNV DNA vaccine using a gene gun were completely protected against SNV infection. This is the first vaccine of any kind that specifically elicits high-titer neutralizing antibodies against SNV. To test the possibility of producing a pan-hantavirus vaccine, rabbits were vaccinated by mEP with an HPS mix (ANDV and SNV plasmids), or HFRS mix (HTNV and PUUV plasmids), or HPS/HFRS mix (all four plasmids). The HPS mix and HFRS mix elicited neutralizing antibodies predominantly against ANDV/SNV and HTNV/PUUV, respectively. Furthermore, the HPS/HFRS mix elicited neutralizing antibodies against all four viruses. These findings demonstrate a pan-hantavirus vaccine using a mixed-plasmid DNA vaccine approach is feasible and warrants further development. PMID:23892100

  15. A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)☆

    PubMed Central

    Hooper, Jay W.; Josleyn, Matthew; Ballantyne, John; Brocato, Rebecca

    2014-01-01

    Sin Nombre virus (SNV; family Bunyaviridae, genus Hantavirus) causes a hemorrhagic fever known as hantavirus pulmonary syndrome (HPS) in North America. There have been approximately 200 fatal cases of HPS in the United States since 1993, predominantly in healthy working-age males (case fatality rate 35%). There are no FDA-approved vaccines or drugs to prevent or treat HPS. Previously, we reported that hantavirus vaccines based on the full-length M gene segment of Andes virus (ANDV) for HPS in South America, and Hantaan virus (HTNV) and Puumala virus (PUUV) for hemorrhagic fever with renal syndrome (HFRS) in Eurasia, all elicited high-titer neutralizing antibodies in animal models. HFRS is more prevalent than HPS (>20,000 cases per year) but less pathogenic (case fatality rate 1–15%). Here, we report the construction and testing of a SNV full-length M gene-based DNA vaccine to prevent HPS. Rabbits vaccinated with the SNV DNA vaccine by muscle electroporation (mEP) developed high titers of neutralizing antibodies. Furthermore, hamsters vaccinated three times with the SNV DNA vaccine using a gene gun were completely protected against SNV infection. This is the first vaccine of any kind that specifically elicits high-titer neutralizing antibodies against SNV. To test the possibility of producing a pan-hantavirus vaccine, rabbits were vaccinated by mEP with an HPS mix (ANDV and SNV plasmids), or HFRS mix (HTNV and PUUV plasmids), or HPS/HFRS mix (all four plasmids). The HPS mix and HFRS mix elicited neutralizing antibodies predominantly against ANDV/SNV and HTNV/PUUV, respectively. Furthermore, the HPS/HFRS mix elicited neutralizing antibodies against all four viruses. These findings demonstrate a pan-hantavirus vaccine using a mixed-plasmid DNA vaccine approach is feasible and warrants further development. PMID:23892100

  16. Immunogenetic Factors Affecting Susceptibility of Humans and Rodents to Hantaviruses and the Clinical Course of Hantaviral Disease in Humans

    PubMed Central

    Charbonnel, Nathalie; Pagès, Marie; Sironen, Tarja; Henttonen, Heikki; Vapalahti, Olli; Mustonen, Jukka; Vaheri, Antti

    2014-01-01

    We reviewed the associations of immunity-related genes with susceptibility of humans and rodents to hantaviruses, and with severity of hantaviral diseases in humans. Several class I and class II HLA haplotypes were linked with severe or benign hantavirus infections, and these haplotypes varied among localities and hantaviruses. The polymorphism of other immunity-related genes including the C4A gene and a high-producing genotype of TNF gene associated with severe PUUV infection. Additional genes that may contribute to disease or to PUUV infection severity include non-carriage of the interleukin-1 receptor antagonist (IL-1RA) allele 2 and IL-1β (-511) allele 2, polymorphisms of plasminogen activator inhibitor (PAI-1) and platelet GP1a. In addition, immunogenetic studies have been conducted to identify mechanisms that could be linked with the persistence/clearance of hantaviruses in reservoirs. Persistence was associated during experimental infections with an upregulation of anti-inflammatory responses. Using natural rodent population samples, polymorphisms and/or expression levels of several genes have been analyzed. These genes were selected based on the literature of rodent or human/hantavirus interactions (some Mhc class II genes, Tnf promoter, and genes encoding the proteins TLR4, TLR7, Mx2 and β3 integrin). The comparison of genetic differentiation estimated between bank vole populations sampled over Europe, at neutral and candidate genes, has allowed to evidence signatures of selection for Tnf, Mx2 and the Drb Mhc class II genes. Altogether, these results corroborated the hypothesis of an evolution of tolerance strategies in rodents. We finally discuss the importance of these results from the medical and epidemiological perspectives. PMID:24859344

  17. Modelling zoonotic diseases in humans: comparison of methods for hantavirus in Sweden

    PubMed Central

    2012-01-01

    Because their distribution usually depends on the presence of more than one species, modelling zoonotic diseases in humans differs from modelling individual species distribution even though the data are similar in nature. Three approaches can be used to model spatial distributions recorded by points: based on presence/absence, presence/available or presence data. Here, we compared one or two of several existing methods for each of these approaches. Human cases of hantavirus infection reported by place of infection between 1991 and 1998 in Sweden were used as a case study. Puumala virus (PUUV), the most common hantavirus in Europe, circulates among bank voles (Myodes glareolus). In northern Sweden, it causes nephropathia epidemica (NE) in humans, a mild form of hemorrhagic fever with renal syndrome. Logistic binomial regression and boosted regression trees were used to model presence and absence data. Presence and available sites (where the disease may occur) were modelled using cross-validated logistic regression. Finally, the ecological niche model MaxEnt, based on presence-only data, was used. In our study, logistic regression had the best predictive power, followed by boosted regression trees, MaxEnt and cross-validated logistic regression. It is also the most statistically reliable but requires absence data. The cross-validated method partly avoids the issue of absence data but requires fastidious calculations. MaxEnt accounts for non-linear responses but the estimators can be complex. The advantages and disadvantages of each method are reviewed. PMID:22984887

  18. The Association between Hantavirus Infection and Selenium Deficiency in Mainland China

    PubMed Central

    Fang, Li-Qun; Goeijenbier, Marco; Zuo, Shu-Qing; Wang, Li-Ping; Liang, Song; Klein, Sabra L.; Li, Xin-Lou; Liu, Kun; Liang, Lu; Gong, Peng; Glass, Gregory E.; van Gorp, Eric; Richardus, Jan H.; Ma, Jia-Qi; Cao, Wu-Chun; de Vlas, Sake J.

    2015-01-01

    Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention. PMID:25609306

  19. Toward a Mechanistic Understanding of Environmentally Forced Zoonotic Disease Emergence: Sin Nombre Hantavirus

    PubMed Central

    Carver, Scott; Mills, James N.; Parmenter, Cheryl A.; Parmenter, Robert R.; Richardson, Kyle S.; Harris, Rachel L.; Douglass, Richard J.; Kuenzi, Amy J.; Luis, Angela D.

    2015-01-01

    Understanding the environmental drivers of zoonotic reservoir and human interactions is crucial to understanding disease risk, but these drivers are poorly predicted. We propose a mechanistic understanding of human–reservoir interactions, using hantavirus pulmonary syndrome as a case study. Crucial processes underpinning the disease's incidence remain poorly studied, including the connectivity among natural and peridomestic deer mouse host activity, virus transmission, and human exposure. We found that disease cases were greatest in arid states and declined exponentially with increasing precipitation. Within arid environments, relatively rare climatic conditions (e.g., El Niño) are associated with increased rainfall and reservoir abundance, producing more frequent virus transmission and host dispersal. We suggest that deer mice increase their occupancy of peridomestic structures during spring–summer, amplifying intraspecific transmission and human infection risk. Disease incidence in arid states may increase with predicted climatic changes. Mechanistic approaches incorporating reservoir behavior, reservoir–human interactions, and pathogen spillover could enhance our understanding of global hantavirus ecology, with applications to other directly transmitted zoonoses. PMID:26955081

  20. Hemorrhagic Fever with Renal Syndrome Caused by 2 Lineages of Dobrava Hantavirus, Russia1

    PubMed Central

    Klempa, Boris; Tkachenko, Evgeniy A.; Dzagurova, Tamara K.; Yunicheva, Yulia V.; Morozov, Vyacheslav G.; Okulova, Natalia M.; Slyusareva, Galina P.; Smirnov, Aleksey

    2008-01-01

    Dobrava-Belgrade virus (DOBV) is a European hantavirus that causes hemorrhagic fever with renal syndrome (HFRS); case-fatality rates in Balkan countries are as high as 12%. To determine causative agents, we examined 126 cases of DOBV-associated HFRS in central and southern European Russia. In central Russia (Lipetsk, Voronezh, Orel regions), outbreaks were caused by a DOBV variant (DOBV-Aa) carried by Apodemus agrarius. In southern Russia (Sochi district), where HFRS is endemic, HFRS cases were caused by a new DOBV variant (DOBV-Ap), found in A. ponticus, a novel hantavirus natural host. Both viruses, DOBV-Aa/Lipetsk and DOBV-Ap/Sochi, were isolated through Vero E6 cells, genetically characterized, and used for serotyping of the HFRS patients’ serum. The clinical severity of HFRS caused by DOBV-Aa resembles that of HFRS caused by Puumala virus (mild to moderate); clinical severity of disease caused by DOBV-Ap infections is more often moderate to severe. PMID:18394280

  1. Hemorrhagic fever with renal syndrome caused by 2 lineages of Dobrava hantavirus, Russia.

    PubMed

    Klempa, Boris; Tkachenko, Evgeniy A; Dzagurova, Tamara K; Yunicheva, Yulia V; Morozov, Vyacheslav G; Okulova, Natalia M; Slyusareva, Galina P; Smirnov, Aleksey; Kruger, Detlev H

    2008-04-01

    Dobrava-Belgrade virus (DOBV) is a European hantavirus that causes hemorrhagic fever with renal syndrome (HFRS); case-fatality rates in Balkan countries are as high as 12%. To determine causative agents, we examined 126 cases of DOBV-associated HFRS in central and southern European Russia. In central Russia (Lipetsk, Voronezh, Orel regions), outbreaks were caused by a DOBV variant (DOBV-Aa) carried by Apodemus agrarius. In southern Russia (Sochi district), where HFRS is endemic, HFRS cases were caused by a new DOBV variant (DOBV-Ap), found in A. ponticus, a novel hantavirus natural host. Both viruses, DOBV-Aa/Lipetsk and DOBV-Ap/Sochi, were isolated through Vero E6 cells, genetically characterized, and used for serotyping of the HFRS patients' serum. The clinical severity of HFRS caused by DOBV-Aa resembles that of HFRS caused by Puumala virus (mild to moderate); clinical severity of disease caused by DOBV-Ap infections is more often moderate to severe. PMID:18394280

  2. Modelling zoonotic diseases in humans: comparison of methods for hantavirus in Sweden.

    PubMed

    Zeimes, Caroline B; Olsson, Gert E; Ahlm, Clas; Vanwambeke, Sophie O

    2012-01-01

    Because their distribution usually depends on the presence of more than one species, modelling zoonotic diseases in humans differs from modelling individual species distribution even though the data are similar in nature. Three approaches can be used to model spatial distributions recorded by points: based on presence/absence, presence/available or presence data. Here, we compared one or two of several existing methods for each of these approaches. Human cases of hantavirus infection reported by place of infection between 1991 and 1998 in Sweden were used as a case study. Puumala virus (PUUV), the most common hantavirus in Europe, circulates among bank voles (Myodes glareolus). In northern Sweden, it causes nephropathia epidemica (NE) in humans, a mild form of hemorrhagic fever with renal syndrome.Logistic binomial regression and boosted regression trees were used to model presence and absence data. Presence and available sites (where the disease may occur) were modelled using cross-validated logistic regression. Finally, the ecological niche model MaxEnt, based on presence-only data, was used.In our study, logistic regression had the best predictive power, followed by boosted regression trees, MaxEnt and cross-validated logistic regression. It is also the most statistically reliable but requires absence data. The cross-validated method partly avoids the issue of absence data but requires fastidious calculations. MaxEnt accounts for non-linear responses but the estimators can be complex. The advantages and disadvantages of each method are reviewed. PMID:22984887

  3. Mapping of the Regions Involved in Homotypic Interactions of Tula Hantavirus N Protein

    PubMed Central

    Kaukinen, Pasi; Vaheri, Antti; Plyusnin, Alexander

    2003-01-01

    Hantavirus nucleocapsid (N) protein has been suggested to form homodimers and homotrimers that are further integrated into the nucleocapsid filaments around the viral RNA. Here we report detailed mapping of the regions involved in the homotypic N protein interactions in Tula hantavirus (TULV). Peptide scan screening was used to define the interaction regions, and the mammalian two-hybrid assay was used for the functional analysis of N protein mutants. To study linear regions responsible for N protein interaction(s), we used peptide scanning in which N peptides synthesized on membranes recognize recombinant TULV N protein. The data showed that the N protein bound to membrane-bound peptides comprising amino acids 13 to 30 and 41 to 57 in the N-terminal part and 340 to 379, 391 to 407, and 410 to 419 in the C-terminal part of the molecule. Further mapping of the interaction regions by alanine scanning indicated the importance of basic amino acids along the N protein and especially asparagine-394, histidine-395, and phenyalanine-396 in forming the binding interface. Analysis of truncated mutants in the mammalian two-hybrid assay showed that N-terminal amino acids 1 to 43 are involved in and C-terminal amino acids 393 to 398 (VNHFHL) are absolutely crucial for the homotypic interactions. Furthermore, our data suggested a tail-to-tail and head-to-head binding scheme for the N proteins. PMID:14512541

  4. Recombination in Tula Hantavirus Evolution: Analysis of Genetic Lineages from Slovakia

    PubMed Central

    Sibold, Claus; Meisel, Helga; Krüger, Detlev H.; Labuda, Milan; Lysy, Jan; Kozuch, Oto; Pejcoch, Milan; Vaheri, Antti; Plyusnin, Alexander

    1999-01-01

    To examine the evolution of Tula hantavirus (TUL), carried by the European common vole (Microtus arvalis and M. rossiaemeridionalis), we have analyzed genetic variants from Slovakia, the country where the virus is endemic. Phylogenetic analysis (PHYLIP) based on either partial (nucleotides [nt] 441 to 898) or complete N-protein-encoding sequences divided Slovakian TUL variants into two main lineages: (i) strains from eastern Slovakia, which clustered with Russian strains, and (ii) strains from western Slovakia situated closer to those from the Czech Republic. We found genetic diversity of 19% between the two groups and 4% within the western Slovakian TUL strains. Phylogenetic analysis of the 3′ noncoding region (3′-NCR), however, placed the eastern Slovakian strains closer to those from western Slovakia and the Czech Republic, with a greater distance to the Russian strains, suggesting a recombinant nature of the S segment in the eastern Slovakian TUL lineage. A bootscan search of the S-segment sequences of TUL strains revealed at least two recombination points in the S sequences of eastern Slovakian TUL strains (nt 400 to 415 and around 1200) which agreed well with the pattern of amino acid substitutions in the N protein and deletions/insertions in the 3′-NCR of the S segment. These data suggest that homologous recombination events occurred in the evolution of hantaviruses. PMID:9847372

  5. Transmission Ecology of Sin Nombre Hantavirus in Naturally Infected North American Deermouse Populations in Outdoor Enclosures

    PubMed Central

    Bagamian, Karoun H.; Towner, Jonathan S.; Kuenzi, Amy J.; Douglass, Richard J.; Rollin, Pierre E.; Waller, Lance A.; Mills, James N.

    2012-01-01

    Sin Nombre hantavirus (SNV), hosted by the North American deermouse (Peromyscus maniculatus), causes hantavirus pulmonary syndrome (HPS) in North America. Most transmission studies in the host were conducted under artificial conditions, or extrapolated information from mark-recapture data. Previous studies using experimentally infected deermice were unable to demonstrate SNV transmission. We explored SNV transmission in outdoor enclosures using naturally infected deermice. Deermice acquiring SNV in enclosures had detectable viral RNA in blood throughout the acute phase of infection and acquired significantly more new wounds (indicating aggressive encounters) than uninfected deermice. Naturally-infected wild deermice had a highly variable antibody response to infection, and levels of viral RNA sustained in blood varied as much as 100-fold, even in individuals infected with identical strains of virus. Deermice that infected other susceptible individuals tended to have a higher viral RNA load than those that did not infect other deermice. Our study is a first step in exploring the transmission ecology of SNV infection in deermice and provides new knowledge about the factors contributing to the increase of the prevalence of a zoonotic pathogen in its reservoir host and to changes in the risk of HPS to human populations. The techniques pioneered in this study have implications for a wide range of zoonotic disease studies. PMID:23110096

  6. Maternal antibodies contribute to sex-based difference in hantavirus transmission dynamics

    PubMed Central

    Kallio, Eva R.; Henttonen, Heikki; Koskela, Esa; Lundkvist, Åke; Mappes, Tapio; Vapalahti, Olli

    2013-01-01

    Individuals often differ in their ability to transmit disease and identifying key individuals for transmission is a major issue in epidemiology. Male hosts are often thought to be more important than females for parasite transmission and persistence. However, the role of infectious females, particularly the transient immunity provided to offspring through maternal antibodies (MatAbs), has been neglected in discussions about sex-biased infection transmission. We examined the effect of host sex upon infection dynamics of zoonotic Puumala hantavirus (PUUV) in semi-natural, experimental populations of bank vole (Myodes glareolus). Populations were founded with either females or males that were infected with PUUV, whereas the other sex was immunized against PUUV infection. The likelihood of the next generation being infected was lower when the infected founders were females, underlying the putative importance of adult males in PUUV transmission and persistence in host populations. However, we show that this effect probably results from transient immunity that infected females provide to their offspring, rather than any sex-biased transmission efficiency per se. Our study proposes a potential contrasting nature of female and male hosts in the transmission dynamics of hantaviruses. PMID:24352416

  7. Theory of hantavirus infection spread incorporating localized adult and itinerant juvenile mice

    NASA Astrophysics Data System (ADS)

    Kenkre, V. M.; Giuggioli, L.; Abramson, G.; Camelo-Neto, G.

    2007-02-01

    A generalized model of the spread of the Hantavirus in mice populations is presented on the basis of recent observational findings concerning the movement characteristics of the mice that carry the infection. The factual information behind the generalization is based on mark-recapture observations reported in Giuggioli et al. [Bull. Math. Biol. 67, 1135 (2005)] that have necessitated the introduction of home ranges in the simple model of Hantavirus spread presented by Abramson and Kenkre [Phys. Rev. E 66, 11912 (2002)]. The essential feature of the model presented here is the existence of adult mice that remain largely confined to locations near their home ranges, and itinerant juvenile mice that are not so confined, and, during their search for their own homes, move and infect both other juveniles and adults that they meet during their movement. The model is presented at three levels of description: mean field, kinetic and configuration. Results of calculations are shown explicitly from the mean field equations and the simulation rules, and are found to agree in some respects and to differ in others. The origin of the differences is shown to lie in spatial correlations. It is indicated how mark-recapture observations in the field may be employed to verify the applicability of the theory.

  8. Statistical mechanical considerations in the theory of the spread of the Hantavirus

    NASA Astrophysics Data System (ADS)

    Kenkre, V. M.

    2005-10-01

    Calculations in the theory of the spread of epidemics are described with particular focus on the estimation of motion parameters describing rodents that are the carriers of the Hantavirus epidemic. The data considered are of the “mark-recapture” kind, i.e., those collected by capturing, tagging and recapturing the animals in a prescribed finite region of space. The theoretical tool used is the Fokker-Planck equation, its characteristic quantities being the diffusion constant which describes the motion of the rodents, and the attractive potential which addresses their tendency to live near their burrows. The measurements are addressed through simple analytical calculations of the mean squared displacement of the animals relevant to the specific probing window in space corresponding to the trapping region. A Fourier prescription is provided to extract the home range of the animals from the observations. Applications of the theory to rodent movement in Panama and New Mexico are mentioned and several on-going generalizations of current models of Hantavirus epidemic spread are introduced.

  9. Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

    PubMed Central

    Golden, Joseph W.; Hammerbeck, Christopher D.; Mucker, Eric M.; Brocato, Rebecca L.

    2015-01-01

    Human pathogenic hantaviruses and arenaviruses are maintained in nature by persistent infection of rodent carrier populations. Several members of these virus groups can cause significant disease in humans that is generically termed viral hemorrhagic fever (HF) and is characterized as a febrile illness with an increased propensity to cause acute inflammation. Human interaction with rodent carrier populations leads to infection. Arenaviruses are also viewed as potential biological weapons threat agents. There is an increased interest in studying these viruses in animal models to gain a deeper understating not only of viral pathogenesis, but also for the evaluation of medical countermeasures (MCM) to mitigate disease threats. In this review, we examine current knowledge regarding animal models employed in the study of these viruses. We include analysis of infection models in natural reservoirs and also discuss the impact of strain heterogeneity on the susceptibility of animals to infection. This information should provide a comprehensive reference for those interested in the study of arenaviruses and hantaviruses not only for MCM development but also in the study of viral pathogenesis and the biology of these viruses in their natural reservoirs. PMID:26266264

  10. Age-related effects of chronic hantavirus infection on female host fecundity.

    PubMed

    Kallio, Eva R; Helle, Heikki; Koskela, Esa; Mappes, Tapio; Vapalahti, Olli

    2015-09-01

    1. Pathogens often cause detrimental effects to their hosts and, consequently, may influence host population dynamics that may, in turn, feed back to pathogen transmission dynamics. Understanding fitness effects of pathogens upon animal host populations can help to predict the risks that zoonotic pathogens pose to humans. 2. Here we determine whether chronic infection by Puumala hantavirus (PUUV) affects important fitness-related traits, namely the probability of breeding, reproductive effort and mother and offspring condition, in the bank vole (Myodes glareolus). Using 9 years empirical data in a PUUV endemic area in Central Finland, we found differences between reproductive characteristics of PUUV-infected and uninfected female bank voles. 3. Young infected females had a significantly higher, and old individuals lower, likelihood of reproducing than uninfected animals during the middle of the breeding season. The implication is that PUUV infection may have long-term deleterious effects that are observed at old age, while in young individuals, the infection may enhance breeding probability by directing resources towards current breeding. 4. Moreover, PUUV infection was related with the mother's body condition. Infected mothers were in poorer condition than uninfected mothers in the early breeding season, but were in better condition than uninfected mothers during the middle of the breeding season. Offspring body condition was positively associated with mother's body condition, which, in turn, was related to the PUUV infection status of the mother. 5. Our findings indicate that chronic infection may affect the reproduction of female hosts, but the effect is dependent on the host age. The effect of chronic hantavirus infection was small and density-independent and hence unlikely to contribute to the cyclic population dynamics of the host. However, the effects on a female's reproductive output might affect the abundance of young susceptible individuals in the

  11. 'Bedside assessment' of acute hantavirus infections and their possible classification into the spectrum of haemophagocytic syndromes.

    PubMed

    Clement, J; Colson, P; Saegeman, V; Lagrou, K; Van Ranst, M

    2016-07-01

    Hantavirus infections, recently renamed 'hantavirus fever' (HTVF), belong to the most common but also most underestimated zoonoses in the world. A small number of reports described the so-called 'lipid paradox' in HTVF, i.e. the striking contrast between a very low serum total cholesterol and/or high-density lipoprotein cholesterol (HDLc), and a paradoxical concomitant hypertriglyceridaemia. In a prospective study, with patients being their own control after illness, we wanted to verify if this quick and easy 'bedside test' was robust enough to warrant a preliminary diagnosis of acute kidney injury (AKI) caused by HTVF. The study cohort consisted of 58 Belgian cases (mean age 44 years), admitted with varying degrees of AKI and of thrombocytopaenia, both characteristic for presumptive HTVF. All cases were sero-confirmed as having acute HTVF. At or shortly after hospital admission, a significant (p < 0.001) decrease of total cholesterol and HDLc was found in comparison with normalised levels in the same cohort, quantified a few days after spontaneous AKI recovery. Conversely, fasting triglyceride levels during HTVF infection were significantly (p < 0.001) higher during illness than after recovery. This 'lipid paradox' was most outspoken in severe HTVF cases, often accompanying, or even predicting, major kidney or lung complications. Thus, this 'bedside assessment' seems to hold even promise for presumptive diagnosis of more severe so-called 'hantavirus cardio-pulmonary syndrome' (HCPS) cases, mostly described hitherto in the New World. In more severe AKI cases, the mean total cholesterol was significantly lower (p = 0.02) than in milder cases, i.e. cases with peak serum creatinine levels of < 1.5 mg/dL. Thrombocytopaenia, generally accepted as the severity index in HTVF, appeared, moreover, significantly correlated with serum levels of total cholesterol (R = 0.52, p < 0.001) and with serum levels of HDLc (R = 0.45, p < 0.01). A link

  12. Urine soluble urokinase-type plasminogen activator receptor levels correlate with proteinuria in Puumala hantavirus infection

    PubMed Central

    Outinen, Tuula K.; Mäkelä, Satu; Huttunen, Reetta; Mäenpää, Niina; Libraty, Daniel; Vaheri, Antti; Mustonen, Jukka; Aittoniemi, Janne

    2014-01-01

    Objectives Urokinase-type plasminogen activator receptor (uPAR) is upregulated during inflammation and known to bind to β3-integrins, receptors used by pathogenic hantaviruses to enter endothelial cells. It has been proposed that soluble uPAR (suPAR) is a circulating factor that causes focal segmental glomerulosclerosis and proteinuria by activating β3-integrin in kidney podocytes. Proteinuria is also a characteristic feature of hantavirus infections. The aim of this study was to evaluate the relation between urine suPAR levels and disease severity in acute Puumala hantavirus (PUUV) infection. Design A single-centre, prospective cohort study. Subjects and methods Urinary suPAR levels were measured twice during the acute phase and once during convalescence in 36 patients with serologically confirmed PUUV infection. Fractional excretion of suPAR (FE suPAR) and of albumin (FE alb) were calculated. Results The FE suPAR was significantly elevated during the acute phase of PUUV infection compared to the convalescent phase (median 3.2%, range 0.8–52.0%, vs. median 1.9%, range 1.0–5.8%, P = 0.005). Maximum FE suPAR was correlated markedly with maximum FE alb (r = 0.812, P < 0.001), and with several other variables that reflect disease severity. There was a positive correlation with the length of hospitalization (r = 0.455, P = 0.009) and maximum plasma creatinine level (r = 0.780, P < 0.001), and an inverse correlation with minimum urinary output (r = −0.411, P = 0.030). There was no correlation between FE suPAR and plasma suPAR (r = 0.180, P = 0.324). Conclusion Urinary suPAR is markedly increased during acute PUUV infection and is correlated with proteinuria. High urine suPAR level may reflect local production of suPAR in the kidney during the acute infection. PMID:24717117

  13. Survey for Hantaviruses, Tick-Borne Encephalitis Virus, and Rickettsia spp. in Small Rodents in Croatia

    PubMed Central

    Dobler, Gerhard; Markotić, Alemka; Kurolt, Ivan-Christian; Speck, Stephanie; Habuš, Josipa; Vucelja, Marko; Krajinović, Lidija Cvetko; Tadin, Ante; Margaletić, Josip; Essbauer, Sandra

    2014-01-01

    Abstract In Croatia, several rodent- and vector-borne agents are endemic and of medical importance. In this study, we investigated hantaviruses and, for the first time, tick-borne encephalitis virus (TBEV) and Rickettsia spp. in small wild rodents from two different sites (mountainous and lowland region) in Croatia. In total, 194 transudate and tissue samples from 170 rodents (A. flavicollis, n=115; A. agrarius, n=2; Myodes glareolus, n=53) were tested for antibodies by indirect immunoflourescence assays (IIFT) and for nucleic acids by conventional (hantaviruses) and real-time RT-/PCRs (TBEV and Rickettsia spp.). A total of 25.5% (24/94) of the rodents from the mountainous area revealed specific antibodies against hantaviruses. In all, 21.3% (20/94) of the samples from the mountainous area and 29.0% (9/31) from the lowland area yielded positive results for either Puumala virus (PUUV) or Dobrava–Belgrade virus (DOBV) using a conventional RT-PCR. All processed samples (n=194) were negative for TBEV by IIFT or real-time RT-PCR. Serological evidence of rickettsial infection was detected in 4.3% (4/94) rodents from the mountainous region. Another 3.2% (3/94) rodents were positive for Rickettsia spp. by real-time PCR. None of the rodents (n=76) from the lowland area were positive for Rickettsia spp. by real-time PCR. Dual infection of PUUV and Rickettsia spp. was found in one M. glareolus from the mountainous area by RT-PCR and real-time PCR, respectively. To our knowledge, this is the first detection of Rickettsia spp. in small rodents from Croatia. Phylogenetic analyses of S- and M-segment sequences obtained from the two study sites revealed well-supported subgroups in Croatian PUUV and DOBV. Although somewhat limited, our data showed occurrence and prevalence of PUUV, DOBV, and rickettsiae in Croatia. Further studies are warranted to confirm these data and to determine the Rickettsia species present in rodents in these areas. PMID:24866325

  14. Genetic detection of Dobrava-Belgrade hantavirus in the edible dormouse (Glis glis) in central Serbia.

    PubMed

    Stanojevic, M; Nikolic, V; Stajkovic, N; Stamenkovic, G; Bozovic, B; Cekanac, R; Marusic, P; Gligic, A

    2015-01-01

    Hantaviruses are endemic in the Balkans, particularly in Serbia, where sporadic cases and/or outbreaks of hantaviral human disease have been reported repeatedly, and evidenced serologically. Here, we present genetic detection of Dobrava-Belgrade virus (DOBV) hantaviral sequences in wild rodents trapped in central Serbia. All the animals were pre-screened serologically by indirect immunofluorescence (IF) test and only those with a positive finding of hantaviral antigens were further tested by polymerase chain reaction. Of the total of 104 trapped animals, 20 were found to be IF positive and of those three were positive for hantaviral RNA: one Microtus arvalis for Tula virus, and one each of Apodemus agrarius and Glis glis for DOBV. Phylogenetic analysis of the obtained sequences implies putative DOBV spillover infection of A. agrarius and G. glis from Apodemus flavicollis. However, future investigations should help to identify the most common natural host and geographical distribution of DOBV in its reservoir hosts in Serbia. PMID:24762257

  15. Neutralizing Antibodies and Sin Nombre Virus RNA after Recovery from Hantavirus Cardiopulmonary Syndrome

    PubMed Central

    Ye, Chunyan; Prescott, Joseph; Nofchissey, Robert; Goade, Diane

    2004-01-01

    Patients who later have a mild course of hantavirus cardiopulmonary syndrome (HCPS) are more likely to exhibit a high titer of neutralizing antibodies against Sin Nombre virus (SNV), the etiologic agent of HCPS, at the time of hospital admission. Because administering plasma from patients who have recovered from HCPS to those in the early stages of disease may be an advantageous form of passive immunotherapy, we examined the neutralizing antibody titers of 21 patients who had recovered from SNV infection. Even 1,000 days after admission to the hospital, 6 of 10 patients had titers of 800 or higher, with one sample retaining a titer of 3,200 after more than 1,400 days. None of the convalescent-phase serum samples contained detectable viral RNA. These results confirm that patients retain high titers of neutralizing antibodies long after recovery from SNV infection. PMID:15109416

  16. Dynamics of Puumala hantavirus infection in naturally infected bank voles (Clethrinomys glareolus).

    PubMed

    Bernshtein, A D; Apekina, N S; Mikhailova, T V; Myasnikov, Y A; Khlyap, L A; Korotkov, Y S; Gavrilovskaya, I N

    1999-01-01

    Specific features of hantavirus infection in bank vole (Clethrionomys glareolus) were studied in the endemic area of hemorrhagic fever with renal syndrome (HFRS) in the foothills of the Ural mountains, using long-term observations on living animals by the capture-mark-recapture (CMR) method. The results demonstrated that the infection naturally circulating in the voles is chronic (lasting for up to 15 months) and asymptomatic, with a peak of Puumala virus accumulation and release from the organism during the first month after infection. It was shown that the bank vole population includes young animals with maternal immunity, which remain resistant to the Puumala virus infection for 3-3.5 months. The infection rate in voles depended on the age and sexual maturity of animals. The greatest proportion of seropositive animals was observed among overwintered males. Seroconversion in voles was more frequent during the period of high reproductive activity. PMID:10664394

  17. Human recombinant Puumala virus antibodies: cross-reaction with other hantaviruses and use in diagnostics.

    PubMed

    Salonen, E M; Parren, P W; Graus, Y F; Lundkvist, A; Fisicaro, P; Vapalahti, O; Kallio-Kokko, H; Vaheri, A; Burton, D R

    1998-04-01

    A panel of seven human monoclonal Fabs against Puumala virus (PUU) nucleocapsid protein (N) was obtained by panning an antibody phage-display library prepared from the spleen of a PUU-immune individual. Three antibodies reacted in immunoblotting and cross-reacted strongly with Tula and Sin Nombre virus recombinant N proteins. These antibodies mapped to the amino terminus of the N protein. One PUU glycoprotein 2 (G2)-specific Fab obtained against a novel epitope (G2c) cross-reacted with Khabarovsk virus but not with the other hantavirus serotypes. An N protein-specific Fab was successfully used as capture antibody to detect PUU-specific serum IgG and IgM antibodies in an enzyme immunoassay. The result demonstrates the usefulness of recombinant human Fabs as potential diagnostic tools. PMID:9568958

  18. The Multimerization of Hantavirus Nucleocapsid Protein Depends on Type-Specific Epitopes

    PubMed Central

    Yoshimatsu, Kumiko; Lee, Byoung-Hee; Araki, Koichi; Morimatsu, Masami; Ogino, Michiko; Ebihara, Hideki; Arikawa, Jiro

    2003-01-01

    Multimerization of the Hantaan virus nucleocapsid protein (NP) in Hantaan virus-infected Vero E6 cells was observed in a competitive enzyme-linked immunosorbent assay (ELISA). Recombinant and truncated NPs of Hantaan, Seoul, and Dobrava viruses lacking the N-terminal 49 amino acids were also detected as multimers. Although truncated NPs of Hantaan virus lacking the N-terminal 154 amino acids existed as a monomer, those of Seoul and Dobrava formed multimers. The multimerized truncated NP antigens of Seoul and Dobrava viruses could detect serotype-specific antibodies, whereas the monomeric truncated NP antigen of Hantaan virus lacking the N-terminal 154 amino acids could not, suggesting that a hantavirus serotype-specific epitope on the NP results in multimerization. The NP-NP interaction was also detected by using a yeast two-hybrid assay. Two regions, amino acids 100 to 125 (region 1) and amino acids 404 to 429 (region 2), were essential for the NP-NP interaction in yeast. The NP of Seoul virus in which the tryptophan at amino acid number 119 was replaced by alanine (W119A mutation) did not multimerize in the yeast two-hybrid assay, indicating that tryptophan 119 in region 1 is important for the NP-NP interaction in yeast. However, W119A mutants expressed in mammalian cells were detected as the multimer by using competitive ELISA. Similarly, the truncated NP of Seoul virus expressing amino acids 155 to 429 showed a homologous interaction in a competitive ELISA but not in the yeast two-hybrid assay, indicating that the C-terminal region is important for the multimerization detected by competitive ELISA. Combined, the results indicate that several steps and regions are involved in multimerization of hantavirus NP. PMID:12502810

  19. Small mammal survival and trapability in mark-recapture monitoring programs for hantavirus.

    PubMed

    Parmenter, C A; Yates, T L; Parmenter, R R; Mills, J N; Childs, J E; Campbell, M L; Dunnum, J L; Milner, J

    1998-01-01

    Following the 1993 hantavirus pulmonary syndrome (HPS) epidemic in the south-western United States, mammalogists and epidemiologists instituted long-term studies to monitor population density and prevalence of infection in rodents which constitute the reservoir for Sin Nombre virus (SNV). In this study, field techniques used in sampling small mammals for SNV infection were evaluated to determine if trapping and handling protocols were having significant effects on future trapability or mortality of animals. We compared rodent mark-recapture control plots, on which all rodents were simply measured, marked, and released on site, with experimental plots on which all animals were anesthetized with methoxyflurane, sampled for blood and saliva, measured, marked, and released. Blood samples were obtained from anesthetized animals on the experimental plots via a retro-orbital sinus puncture using a heparinized capillary tube. Dacron tipped oral swabs were used to collect buccal cells and saliva from the rodent's oral cavity. Field data were collected monthly from August 1994 to August 1996 at two sites in New Mexico (USA). Analyses were based on 3,661 captures of 1,513 individuals representing 21 species from three rodent families (Rodentia: Muridae, Heteromyidae, Sciuridae) and two species of rabbits (Lagomorpha: Leporidae). Overall, for most murid rodents (including five Peromyscus spp., Neotoma albigula, and Onychomys leucogaster) and one rabbit species (Sylvilagus floridanus), the handling/bleeding procedures had no significant effects on recapture rates or mortality. In contrast, several species of heteromyids (Dipodomys ordii and Perognathus flavus), one murid (Reithrodontomys megalotis) and one leporid (S. auduboni) suffered higher mortality rates, and heteromyid kangaroo rats (D. ordii and D. merriami) exhibited lower trapability as a result of the anesthesia and sampling procedures. In view of the overall non-significant influence of the sampling procedures on

  20. Mapping of B-cell epitopes in the nucleocapsid protein of Puumala hantavirus.

    PubMed

    Lundkvist, A; Meisel, H; Koletzki, D; Lankinen, H; Cifire, F; Geldmacher, A; Sibold, C; Gött, P; Vaheri, A; Krüger, D H; Ulrich, R

    2002-01-01

    Hantavirus nucleocapsid protein (N) has been proven to induce highly protective immune responses in animal models. The knowledge on the mechanisms behind N-induced protection is still limited, although recent data suggest that both cellular and humoral immune responses are of importance. For a detailed B-cell epitope mapping of Puumala hantavirus (PUUV) N, we used recombinant N derivatives of the Russian strain CG18-20 and the Swedish strain Vranica/Hällnäs, as well as overlapping synthetic peptides corresponding to the Finnish prototype strain Sotkamo. The majority of a panel of monoclonal antibodies (mAbs) reacted with proteins derived from all included PUUV strains demonstrating the antigenic similarity of these proteins. In line with previous results, the epitopes of most mAbs were mapped within the 80 N-terminal amino acids of N. The present study further revealed that the epitopes of four mAbs raised against native viral N were located within amino acids 14-45, whereas one mAb raised against recombinant N was mapped to amino acids 14-39. Differences between the reactivity of the PUUV strains Vranica/Hällnäs and CG18-20 N suggested the importance of amino acid position 35 for the integrity of the epitopes. In line with the patterns obtained by the truncated recombinant proteins, mapping by overlapping peptides (PEPSCAN) confirmed a complex recognition pattern for most analyzed mAbs. Together, the results revealed the existence of several, partially overlapping, and discontinuous B-cell epitopes. In addition, based on differences within the same competition group, novel epitopes were defined. PMID:11952140

  1. Rapid and specific detection of Sin Nombre virus antibodies in patients with hantavirus pulmonary syndrome by a strip immunoblot assay suitable for field diagnosis.

    PubMed Central

    Hjelle, B; Jenison, S; Torrez-Martinez, N; Herring, B; Quan, S; Polito, A; Pichuantes, S; Yamada, T; Morris, C; Elgh, F; Lee, H W; Artsob, H; Dinello, R

    1997-01-01

    To develop a rapid antibody test for Sin Nombre hantavirus (SNV) infection for diagnosis of hantavirus pulmonary syndrome (HPS) in field settings where advanced instrumentation is not available, a strip immunoblot assay bearing four immobilized antigens for SNV and a recombinant nucleocapsid protein antigen of Seoul hantavirus (SEOV) was prepared. The SNV antigens included a full-length recombinant-expressed nucleocapsid (N) protein (rN), a recombinant-expressed G1 protein (residues 35 to 117), and synthetic peptides derived from N (residues 17 to 59) and G1 (residues 55 to 88). On the basis of the observed reactivities of hantavirus-infected patient and control sera, we determined that a positive assay requires reactivity with SNV or SEOV rN antigen and at least one other antigen. Isolated reactivity to either viral rN antigen is indeterminate, and any pattern of reactivity that does not include reactivity to an rN antigen is considered indeterminate but is unlikely to represent hantavirus infection. Fifty-eight of 59 samples from patients with acute SNV-associated HPS were positive according to these criteria, and one was initially indeterminate. Four of four samples from patients with HPS due to other hantaviruses were positive, as were most samples from patients with SEOV and Puumala virus infections. Of 192 control serum samples, 2 (1%) were positive and 2 were indeterminate. Acute SNV infection was distinguishable from remote SNV infection or infection with hantaviruses other than SNV by the presence of G1 peptide antigen reactivities in the former. The strip immunoblot assay shows promise for the detection of SNV antibodies early in the course of HPS. PMID:9041397

  2. Ecology and demographics of hantavirus infections in rodent populations in the Walker River Basin of Nevada and California.

    PubMed

    Boone, J D; Otteson, E W; McGwire, K C; Villard, P; Rowe, J E; St Jeor, S C

    1998-09-01

    To study the ecologic correlates of hantavirus in deer mice (Peromyscus maniculatus), we sampled 114 sites in the Walker River Basin of Nevada and California in 1995-1996. Blood samples were tested for antibody to hantavirus, and a subset of samples was also tested for virus RNA by reverse transcription-polymerase chain reaction. Average prevalence of antibody-positive mice was 17%, with heavier males the most likely to be infected. Antibody prevalence varied within repeatedly sampled sites from 0% to 50% over the course of several months, suggesting possible infection cycles. Although there was no linear correlation between deer mouse density and antibody prevalence on sample sites, more complex relationships between density and prevalence appeared likely. Specifically, infections were less likely where rodent densities were lower than a critical threshold value. However, above this value, density had no effect on prevalence. PMID:9749642

  3. Bayou virus-associated hantavirus pulmonary syndrome in Eastern Texas: identification of the rice rat, Oryzomys palustris, as reservoir host.

    PubMed Central

    Torrez-Martinez, N.; Bharadwaj, M.; Goade, D.; Delury, J.; Moran, P.; Hicks, B.; Nix, B.; Davis, J. L.; Hjelle, B.

    1998-01-01

    We describe the third known case of hantavirus pulmonary syndrome (HPS) due to Bayou virus, from Jefferson County, Texas. By using molecular epidemiologic methods, we show that rice rats (Oryzomys palustris) are frequently infected with Bayou virus and that viral RNA sequences from HPS patients are similar to those from nearby rice rats. Bayou virus is associated with O. palustris; this rodent appears to be its predominant reservoir host. PMID:9452404

  4. A temporal dilution effect: hantavirus infection in deer mice and the intermittent presence of voles in Montana.

    PubMed

    Carver, Scott; Kuenzi, Amy; Bagamian, Karoun H; Mills, James N; Rollin, Pierre E; Zanto, Susanne N; Douglass, Richard

    2011-07-01

    The effect of intermittently occurring, non-reservoir host species on pathogen transmission and prevalence in a reservoir population is poorly understood. We investigated whether voles, Microtus spp., which occur intermittently, influenced estimated standing antibody prevalence (ESAP) to Sin Nombre hantavirus (SNV, Bunyaviridae: Hantavirus) among deer mice, Peromyscus maniculatus, whose populations are persistent. We used 14 years of data from central Montana to investigate whether ESAP among deer mice was related to vole presence or abundance while controlling for the relationship between deer mouse abundance and ESAP. We found a reduction in deer mouse ESAP associated with the presence of voles, independent of vole abundance. A number of studies have documented that geographic locations which support a higher host diversity can be associated with reductions in pathogen prevalence by a hypothesized dilution effect. We suggest a dilution effect may also occur in a temporal dimension at sites where host richness fluctuates. Preservation of host diversity and optimization of environmental conditions which promote occurrence of ephemeral species, such as voles, may result in a decreased ESAP to hantaviruses among reservoir hosts. Our results may extend to other zoonotic infectious diseases. PMID:21170746

  5. A temporal dilution effect: hantavirus infection in deer mice and the intermittent presence of voles in Montana

    PubMed Central

    Kuenzi, Amy; Bagamian, Karoun H.; Mills, James N.; Rollin, Pierre E.; Zanto, Susanne N.; Douglass, Richard

    2011-01-01

    The effect of intermittently occurring, non-reservoir host species on pathogen transmission and prevalence in a reservoir population is poorly understood. We investigated whether voles, Microtus spp., which occur intermittently, influenced estimated standing antibody prevalence (ESAP) to Sin Nombre hantavirus (SNV, Bunyaviridae: Hantavirus) among deer mice, Peromyscus maniculatus, whose populations are persistent. We used 14 years of data from central Montana to investigate whether ESAP among deer mice was related to vole presence or abundance while controlling for the relationship between deer mouse abundance and ESAP. We found a reduction in deer mouse ESAP associated with the presence of voles, independent of vole abundance. A number of studies have documented that geographic locations which support a higher host diversity can be associated with reductions in pathogen prevalence by a hypothesized dilution effect. We suggest a dilution effect may also occur in a temporal dimension at sites where host richness fluctuates. Preservation of host diversity and optimization of environmental conditions which promote occurrence of ephemeral species, such as voles, may result in a decreased ESAP to hantaviruses among reservoir hosts. Our results may extend to other zoonotic infectious diseases. PMID:21170746

  6. Interferons Induce STAT1-Dependent Expression of Tissue Plasminogen Activator, a Pathogenicity Factor in Puumala Hantavirus Disease.

    PubMed

    Strandin, Tomas; Hepojoki, Jussi; Laine, Outi; Mäkelä, Satu; Klingström, Jonas; Lundkvist, Åke; Julkunen, Ilkka; Mustonen, Jukka; Vaheri, Antti

    2016-05-15

    Hantaviruses are zoonotic viruses that show various degrees of vasculopathy in humans. In this study, we analyzed the regulation of 2 fibrinolytic parameters, tissue plasminogen activator (tPA) and its physiological inhibitor, plasminogen activator inhibitor 1 (PAI-1), in Puumala hantavirus (PUUV)-infected patients and in human microvascular endothelial cells. We detected strong upregulation of tPA in the acute phase of illness and in PUUV-infected macaques and found the tPA level to positively correlate with disease severity. The median levels of PAI-1 during the acute stage did not differ from those during the recovery phase. In concordance, hantaviruses induced tPA but not PAI-1 in microvascular endothelial cells, and the induction was demonstrated to be dependent on type I interferon. Importantly, type I and II interferons directly upregulated tPA through signal transducer and activator of transcription 1 (STAT1), which regulated tPA gene expression via a STAT1-responsive enhancer element. These results suggest that tPA may be a general factor in the immunological response to viruses. PMID:26704613

  7. Variability of G1 gene of hantaviruses occurring in the Hubei Province, P.R. China from 1985 to 2000.

    PubMed

    Li, Q; Yang, Z Q; Qu, H; Xiao, H

    2005-01-01

    We studied variability of G1 gene of hantaviruses occurring in the Hubei province, P.R. China. Serum samples were collected from 229 patients with hemorrhagic fever with renal syndromes (HFRS) during 1985--1989 and 1996--2000 and were tested by RT-PCR for the presence of Hantaan and Seoul viruses (HTNVs, SEOVs) and by restriction fragment length polymorphism (RFLP) analysis for the respective pattern. Out of 229 sera 166 (72.5%) were hantavirus-positive by RT-PCR, including 124 from 1985--1989 and 42 from 1996--2000, with HTNVs in majority (80.1%) and SEOVs in minority (19.9%). By RFLP analysis, four types of RFLP pattern were recognized. In the 133 HTNV isolates the A pattern was most predominant (62.5%), while the remaining patterns B, C, and D were present in minority. This kind of the RFLP pattern distribution was observed regardless the year of virus isolation. In contrast, only one type of RFLP pattern was obtained from 33 SEOVs, but this was different from that of R22 virus. Our results indicate that temporal factor, represented by years 1985--2000 seems to be too short to affect markedly the genetic makeup of the hantaviruses investigated. PMID:15929399

  8. Preliminary selection and evaluation of the binding of aptamers against a Hantavirus antigen using fluorescence spectroscopy and modeling

    NASA Astrophysics Data System (ADS)

    Missailidis, Sotiris; de Oliveira, Renata Carvalho; Silva, Dilson; Cortez, Célia Martins; Guterres, Alexandro; Vicente, Luciana Helena Bassan; de Godoy, Daniela Tupy; Lemos, Elba

    2015-12-01

    In this study we have aimed to develop novel aptamers against the Hantavirus nucleoprotein N, a valid antigen already used in the Hantavirus reference laboratory of the Institute Oswaldo Cruz in Rio de Janeiro, Brazil. Such aptamers, if they are found to bind with high affinity and specificity for the selected hantavirus antigen, they could be translated into novel diagnostic assays with the ability to provide early detection for hantaviroses and their related disease syndromes. In a preliminary screening, we have managed to identify three aptamer species. We have analyzed a short and a long version of these aptamer using fluorescence spectroscopy and modelled their binding. We have identified Stern-Volmer constants for the selected aptamers, which have shown affinity for their target, with a different binding between the short and the long versions of them. Short aptamers have shown to have a higher Stern-Volmer constant and the ability to potentially bind to more than one binding site on the antigen. The information provided by the spectroscopic screening has been invaluable in allowing us to define candidates for further development into diagnostic assays.

  9. Acidification triggers Andes hantavirus membrane fusion and rearrangement of Gc into a stable post-fusion homotrimer.

    PubMed

    Acuña, Rodrigo; Bignon, Eduardo A; Mancini, Roberta; Lozach, Pierre-Yves; Tischler, Nicole D

    2015-11-01

    The hantavirus membrane fusion process is mediated by the Gc envelope glycoprotein from within endosomes. However, little is known about the specific mechanism that triggers Gc fusion activation, and its pre- and post-fusion conformations. We established cell-free in vitro systems to characterize hantavirus fusion activation. Low pH was sufficient to trigger the interaction of virus-like particles with liposomes. This interaction was dependent on a pre-fusion glycoprotein arrangement. Further, low pH induced Gc multimerization changes leading to non-reversible Gc homotrimers. These trimers were resistant to detergent, heat and protease digestion, suggesting characteristics of a stable post-fusion structure. No acid-dependent oligomerization rearrangement was detected for the trypsin-sensitive Gn envelope glycoprotein. Finally, acidification induced fusion of glycoprotein-expressing effector cells with non-susceptible CHO cells. Together, the data provide novel information on the Gc fusion trigger and its non-reversible activation involving lipid interaction, multimerization changes and membrane fusion which ultimately allow hantavirus entry into cells. PMID:26310672

  10. Hantavirus Infections

    MedlinePlus

    ... breathe infected air or come into contact with rodents or their urine or droppings. You cannot catch ... symptoms include coughing and shortness of breath. Controlling rodents in and around your house is the best ...