epidemiologyЭпидемиология и ВакцинопрофилактикаEpidemiology and Vaccinal Prevention2073-30462619-0494«Numicom» LLC10.31631/2073-3046-2017-16-3-26-32epidemiology-273Research ArticleОФИЦИАЛЬНАЯ ИНФОРМАЦИЯOFFICIAL INFORMATIONХарактеристика хантавирусов - возбудителей зоонозных геморрагических лихорадокCharacteristics of Hantaviruses as Causative Agents of the Zoonotic Hemorrhagic FeversИшмухаметовА. А.IshmukhametovA. A.noemail@neicon.ruДзагуроваТ. К.DzagurovaT. K.noemail@neicon.ruМорозовВ. Г.MorozovV. G.noemail@neicon.ruКурашоваС. С.KurashovaC. C.noemail@neicon.ruБаловневаМ. В.BalovnevaM. V.noemail@neicon.ruСоцковаС. Е.SotskovaC. E.noemail@neicon.ruТкаченкоЕ. А.TkachenkoE. A.evgeniytkach@mail.ruФГБНУ «Федеральный научный центр исследований и разработки иммунобиологических препаратов им. М.П.Чумакова РАН», ФАНО России; ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова Минздрава России; ООО «Гепатолог»РоссияFederal State Budget Institution of Science «Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences»; Federal State Autonomous Educational Institution of Higher Education «I.M. Sechenov First Moscow State Medical University» of the Ministry of Healthcare of the Russian Federation; LLC «Hepatolog»Russian FederationФГБНУ «Федеральный научный центр исследований и разработки иммунобиологических препаратов им. М.П.Чумакова РАН», ФАНО РоссииРоссияFederal State Budget Institution of Science «Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences»Russian Federation2017200620171632632Copyright © Ишмухаметов А.А., Дзагурова Т.К., Морозов В.Г., Курашова С.С., Баловнева М.В., Соцкова С.Е., Ткаченко Е.А., 20172017Ишмухаметов А.А., Дзагурова Т.К., Морозов В.Г., Курашова С.С., Баловнева М.В., Соцкова С.Е., Ткаченко Е.А.Ishmukhametov A.A., Dzagurova T.K., Morozov V.G., Kurashova C.C., Balovneva M.V., Sotskova C.E., Tkachenko E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.epidemvac.ru/jour/article/view/273

Геморрагическая лихорадка с почечным синдромом (ГЛПС) на протяжении уже многих лет представляет значительную проблему для здравоохранения многих стран Евразийского континента. В 70-80х были обнаружены вирусы, вызывающие ГЛПС, которые вместе с другими близко родственными, но не патогенными для человека вирусами, составили новый род Hantavirus семейства Bunyaviridae. В результате изучения вспышки тяжелого заболевания на юго-западе США в 1993 г., было показано, что возбудителем заболевания также является хантавирус. Болезнь впоследствии получила название хантавирусный пульмональный синдром (ХПС). В настоящее время установлено широкое распространение хантавирусов, носителями которых в природе являются различные виды грызунов. Хантавирусы вызывают хроническую бессимптомную инфекцию у грызунов и передаются человеку аэрогенным путём через экскреты инфицированных животных. Долгое время исследования хантавирусов были ограничены их высокой патогенностью, отсутствием лабораторной модели инфекции на животных и низким уровнем размножения вируса в клеточных культурах. За последние годы, благодаря стремительному прогрессу в разработке и применении молекулярно-биологических методов, были достигнуты значительные успехи в исследованиях хантавирусов. В настоящем обзоре представлены данные, касающиеся изучения различных аспектов экологии, молекулярной биологии, морфологии, патогенеза, диагностики и других характеристик хантавирусов.

Hemorrhagic fever with renal syndrome (HFRS) has been a major concern for public health in different countries of the Euroasian continent for decades. In 1970s the disease was associated with newly discovered viruses that were to become new members (under the genus Hantavirus) of the family Bunyaviridae. During a deadly outbreak of pulmonary syndrome in the southwestern United States in 1993, it was shown that causative agents of this devastating disease (designated hantavirus cardio-pulmonary syndrome, HCPS) were also hantaviruses. By now hantaviruses are found worldwide and associated with different species of the order Rodentia , which are their natural carriers. Hantaviruses persistently infect rodents, however do not cause any disease in them and are transmitted to humans through aerosolized excreta. For a long time studies of hantaviruses were limited by their high pathogenicity, absence of animal model of infection, and poor growth in cell cultures. With the rapid development of molecular biological techniques in last several years substantial progress has been made in various fields of hantavirus research. Different aspects of hantavirus ecology, molecular biology, morphology and pathogenesis, as well as current diagnostic methods and other characteristics of hantaviruses are considered in this review.

хантавирусГЛПСХПСhantavirusHFRSHPSReferencesLee H.W., Lee PW., Johnson K.M. Isolation of the etiologic agent of Korean hemorrhagic fever. J Infect Dis. 1978; 137: 298 - 308.Lee H.W., Lee P.W., Johnson K.M. Isolation of the etiologic agent of Korean hemorrhagic fever. J Infect Dis. 1978; 137: 298 – 308.Schmaljohn C., Dalrymple J. Analysis of Hantaan virus RNA: evidence for a new genus of Bunyaviridae. Virology. 1983; 131: 482 - 491.Schmaljohn C., Dalrymple J. Analysis of Hantaan virus RNA: evidence for a new genus of Bunyaviridae. Virology. 1983; 131: 482 – 491.Nichol S.T., Spiropoulou C.F., Morzunov S., Rollin P.E., Ksiazek T.G., Feldmann H, et al. Genetic identi cation of a hantavirus associated with an outbreak of acute respiratory illness. Science. 1993; 262 (5135): 91 4 - 917.Nichol S.T., Spiropoulou C.F., Morzunov S., Rollin P.E., Ksiazek T.G., Feldmann H, et al. Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness. Science. 1993; 262 (5135): 91 4 – 917.Schmaljohn C., Hjelle B. Hantaviruses: a global disease problem. Emerg Infect Dis. 1997; 3 (2): 95 - 104.Schmaljohn C., Hjelle B. Hantaviruses: a global disease problem. Emerg Infect Dis. 1997; 3 (2): 95 – 104.Plyusnin A., Morzunov S.P. Virus evolution and genetic diversity of hantaviruses and their rodent hosts. Curr Top Microbiol Immunol. 2001; 256: 47 - 75.Plyusnin A., Morzunov S.P. Virus evolution and genetic diversity of hantaviruses and their rodent hosts. Curr Top Microbiol Immunol. 2001; 256: 47 – 75.Yashina L., Abramov S., Gutorov V. et al. Seewis virus: phylogeography of a shrew-borne hantavirus in Siberia, Russia.Vector Borne Zoonotic Dis. 2010; 10(6):585 - 591.Yashina L., Abramov S., Gutorov V. et al. Seewis virus: phylogeography of a shrew-borne hantavirus in Siberia, Russia.Vector Borne Zoonotic Dis. 2010; 10(6):585 – 591.Bennett S.N., Gu S.H., Kang H.J., Arai S., Yanagihara R. Reconstructing the evolutionary origins and phylogeography of hantaviruses. Trends Microbiol. 2014; 8: 473 - 482.Bennett S.N., Gu S.H., Kang H.J., Arai S., Yanagihara R. Reconstructing the evolutionary origins and phylogeography of hantaviruses. Trends Microbiol. 2014; 8: 473 – 482.Novotny N., Weissenboeck H., Aberle S., Hinterdorfer F. Hantavirus infection in the domestic cat. JAMA. 1994; 4: 1100 - 1101.Novotny N., Weissenboeck H., Aberle S., Hinterdorfer F. Hantavirus infection in the domestic cat. JAMA. 1994; 4: 1100 – 1101.Slonova R.A., Tkachenko E.A., Kushnarev E.L., Dzagurova T.K., Astakova T.I. Hantavirus isolation from birds. Acta virol. 1992; 36: 493.Slonova R.A., Tkachenko E.A., Kushnarev E.L., Dzagurova T.K., Astakova T.I. Hantavirus isolation from birds. Acta virol. 1992; 36: 493.Malecki, T.M., G.P. Jillson, J.P. Thilsted, J. et al. Serologic survey for hantavirus infection in domestic animals and coyotes from New Mexico and northeastern Arizona. J Am Vet Med Assoc. 1998; 212 (7): 970 - 973.Malecki, T.M., G.P. Jillson, J.P. Thilsted, J. et al. Serologic survey for hantavirus infection in domestic animals and coyotes from New Mexico and northeastern Arizona. J Am Vet Med Assoc. 1998; 212 (7): 970 – 973.Danes L., Pejcoch M., Bukovjan K., Veleba J., Halackova M. Antibodies against Hantaviruses in game and domestic oxen in the Czech Republic. Cesk. Epidemiol. Mikrobiol. Imunol. 1992; 41.(1):.15 - 18.Danes L., Pejcoch M., Bukovjan K., Veleba J., Halackova M. Antibodies against Hantaviruses in game and domestic oxen in the Czech Republic. Cesk. Epidemiol. Mikrobiol. Imunol. 1992; 41.(1):.15 – 18.Maes P., Clement J., Gavrilovskaya I. Hantaviruses: Immunology, Treatment, and Prevention. Viral. Immunol. 2004; 17 (4): 481 - 497.Maes P., Clement J., Gavrilovskaya I. Hantaviruses: Immunology, Treatment, and Prevention. Viral. Immunol. 2004; 17 (4): 481 – 497.McCormick J., Palmer E., Sasso D., Kiley M. Morphological identification of the agent of Korean hemorrhagic fever (Hantaan virus) as a members of the Bunyaviridae. Lancet. 1982; 3: 765 - 768.McCormick J., Palmer E., Sasso D., Kiley M. Morphological identification of the agent of Korean hemorrhagic fever (Hantaan virus) as a members of the Bunyaviridae. Lancet. 1982; 3: 765 – 768.Battisti A.J., Chu Y.-K., Chipman P.R., Kaufmann B., Jonsson C.B., Rossmann M.G. Structural Studies of Hantaan Virus. J. Virol. 2011; 85 (2): 835 - 841.Battisti A.J., Chu Y.-K., Chipman P.R., Kaufmann B., Jonsson C.B., Rossmann M.G. Structural Studies of Hantaan Virus. J. Virol. 2011; 85 (2): 835 – 841.Schmaljohn C., Hasty S., Harrison S., Dalrymple J. Characterization of Hantaan virions, the prototype virus of HFRS. J. Infect. Dis. 1983; 148: 1005 - 1012.Schmaljohn C., Hasty S., Harrison S., Dalrymple J. Characterization of Hantaan virions, the prototype virus of HFRS. J. Infect. Dis. 1983; 148: 1005 – 1012.Schmaljohn C., Jennings G., Hay J., Dalrymple J. Coding strategy of the S-genome segment of Hantaan virus. Virology. 1986; 155: 633 - 643.Schmaljohn C., Jennings G., Hay J., Dalrymple J. Coding strategy of the S-genome segment of Hantaan virus. Virology. 1986; 155: 633 – 643.Schmaljohn C., Schmaljohn A., Dalrymple J. Hantaan virus M RNA: Coding strategy, nucleotide sequence, and gene order. Virology. 1987; 157: 31 - 39.Schmaljohn C., Schmaljohn A., Dalrymple J. Hantaan virus M RNA: Coding strategy, nucleotide sequence, and gene order. Virology. 1987; 157: 31 – 39.Schmaljohn C. Nucleotide sequence of the L genome segment of Hantaan virus. Nucleic Acids Res. 1990; 18: 6728.Schmaljohn C. Nucleotide sequence of the L genome segment of Hantaan virus. Nucleic Acids Res. 1990; 18: 6728.Gavrilovskaya, I.N., M. Shepley, R. Shaw, M.H. Ginsberg, and E.R. Mackow. Beta3 Integrins mediate the cellular entry of hantaviruses that cause respiratory failure. Proc. Natl. Acad. Sci. USA. 1998; 95 (12): 7074 - 7079.Gavrilovskaya, I.N., M. Shepley, R. Shaw, M.H. Ginsberg, and E.R. Mackow. Beta3 Integrins mediate the cellular entry of hantaviruses that cause respiratory failure. Proc. Natl. Acad. Sci. USA. 1998; 95 (12): 7074 – 7079.Garcin D., Lezzi M., Dobbs M., Elliott R.M., Schmaljohn C., Kang C.Y., Kolakofsky D. The 5’ends of Hantaan virus (Bunyaviridae) RNAs suggest a prime-and-realign mechanism for the initiation of RNA synthesis. Virol. 1995; 69: 5754 - 5762.Garcin D., Lezzi M., Dobbs M., Elliott R.M., Schmaljohn C., Kang C.Y., Kolakofsky D. The 5’ends of Hantaan virus (Bunyaviridae) RNAs suggest a prime-andrealign mechanism for the initiation of RNA synthesis. Virol. 1995; 69: 5754 – 5762.Pensiero M., Hay J. The Hantaan virus M-segment glycoproteins G1 and G2 can be expressed independently. J. Virol. 1992; 66: 1907 - 1914.Pensiero M., Hay J. The Hantaan virus M-segment glycoproteins G1 and G2 can be expressed independently. J. Virol. 1992; 66: 1907 – 1914.Lober C., Anheier B., Lindow S., Klenk H., Feldmann H. The Hantaan virus glycoprotein precursor is cleaved at the conserved pentapeptide WAASA. Virology. 2001; 289:224-229Lober C., Anheier B., Lindow S., Klenk H., Feldmann H. The Hantaan virus glycoprotein precursor is cleaved at the conserved pentapeptide WAASA. Virology. 2001; 289:224-229Spiropoulou C., Goldsmith C., Shoemaker T. Peters C.J., Compans R. Sin Nombre virus glycoprotein trafficking. Virology. 2003; 308: 48 - 63.Spiropoulou C., Goldsmith C., Shoemaker T. Peters C.J., Compans R. Sin Nombre virus glycoprotein trafficking. Virology. 2003; 308: 48 – 63.Pettersson R. Protein localization and virus assembly at intracellular membranes. Curr. Top. Microbiol. Immunol. 1991; 170: 67 - 106.Pettersson R. Protein localization and virus assembly at intracellular membranes. Curr. Top. Microbiol. Immunol. 1991; 170: 67 – 106.Arikawa J., Yao J.S., Yoshimatsu K., Takashima I., Hashimoto N. Protective role of antigenic sites on the envelope protein of Hantaan virus defined by monoclonal antibodies. Arch Virol. 1992; 126 (1 - 4): 271 - 281.Arikawa J., Yao J.S., Yoshimatsu K., Takashima I., Hashimoto N. Protective role of antigenic sites on the envelope protein of Hantaan virus defined by monoclonal antibodies. Arch Virol. 1992; 126 (1 – 4): 271 – 281.Dzagurova T.K., Tkachenko E.A., Slonova R.A., Ivanov L.I., Ivanidze E.A., Markeshin S. et al. Antigenic relationships of hantavirus strains analysed by monoclonal antibodies. Arch Virol. 1995; 140: 1763 - 1773.Dzagurova T.K., Tkachenko E.A., Slonova R.A., Ivanov L.I., Ivanidze E.A., Markeshin S. et al. Antigenic relationships of hantavirus strains analysed by monoclonal antibodies. Arch Virol. 1995; 140: 1763 – 1773.Bautz E., Zoller L., Darai G. Recent developments in Hantavirus diagnostics and epitope mapping. Abstracts of 3rd Intern. Conf. оп HFRS and Hantaviruses. Helsinki, Finland. 1995; 45Bautz E., Zoller L., Darai G. Recent developments in Hantavirus diagnostics and epitope mapping. Abstracts of 3rd Intern. Conf. оn HFRS and Hantaviruses. Helsinki, Finland. 1995; 45Elliott R.M., Bouloy M., Calisher C.H., Goldbach R., Moyer J.T., Nichol S.T. et al. Virus taxonomy: classification and nomenclature of viruses. 7th report of the International Committee on Taxonomy of Viruses. Bunyaviridae. Academic Press, San Diego, Calif. 2000: 599 - 621.Elliott R.M., Bouloy M., Calisher C.H., Goldbach R., Moyer J.T., Nichol S.T. et al. Virus taxonomy: classification and nomenclature of viruses. 7th report of the International Committee on Taxonomy of Viruses. Bunyaviridae. Academic Press, San Diego, Calif. 2000: 599 – 621.Song K., Kim S., Choi Y. et al. Molecular phylogeny of Hantaan virus, the prototype virus of HFRS. 3rd Intern. Conf. on HFRS and Hantaviruses, Helsinki. 1995: 48.Song K., Kim S., Choi Y. et al. Molecular phylogeny of Hantaan virus, the prototype virus of HFRS. 3rd Intern. Conf. on HFRS and Hantaviruses, Helsinki. 1995: 48.Plyusnin A., Vapalahti O., Ulfves K. Sequences of wild Puumala virus genes show a correlation of genetic variation with geographic origin of the strains. J. Gen. Virol. 1994; 75: 405 - 409.Plyusnin A., Vapalahti O., Ulfves K. Sequences of wild Puumala virus genes show a correlation of genetic variation with geographic origin of the strains. J. Gen. Virol. 1994; 75: 405 – 409.Henderson W., Monroe M., St. Jeor S., Thayer S.C., Rowe W.P., Peters J.E. et al. Naturally occurring Sin Nombre virus genetic reassortants. Virology. 1995; 214: 602 - 610.Henderson W., Monroe M., St. Jeor S., Thayer S.C., Rowe W.P., Peters J.E. et al. Naturally occurring Sin Nombre virus genetic reassortants. Virology. 1995; 214: 602 – 610.Lundkvist A., Hukic M., Horling J., Gilljam M., Nichol S., Niklasson B. Puumala and Dobrava viruses cause hemorrhagic fever with renal syndrome in Bosnia-Herzegovina: evidence of highly cross-neutralizing antibody responses in early patient sera. J. Med. Virol. 1997; 53 (1): 51 - 59.Lundkvist A., Hukic M., Horling J., Gilljam M., Nichol S., Niklasson B. Puumala and Dobrava viruses cause hemorrhagic fever with renal syndrome in Bosnia- Herzegovina: evidence of highly cross-neutralizing antibody responses in early patient sera. J. Med. Virol. 1997; 53 (1): 51 – 59.Plyusnin A., Cheng Y., Lehvaslaiho H., Vaheri A. Quasispecies in wild Tula hantavirus population. J. Virol. 1996; 70: 9060 - 9063.Plyusnin A., Cheng Y., Lehvaslaiho H., Vaheri A. Quasispecies in wild Tula hantavirus population. J. Virol. 1996; 70: 9060 – 9063.Razzauti M., Plysunina A., Sironen T., Henttonen H., Plyusnin A. Analysis of Puumala hantavirus in a bank vole population in northern Finland: evidence for co-circulation of two genetic lineages and frequent reassortment between wild-type strains. J. Gen. Virol. 2009; 90: 1923 - 1931.Razzauti M., Plysunina A., Sironen T., Henttonen H., Plyusnin A. Analysis of Puumala hantavirus in a bank vole population in northern Finland: evidence for co- circulation of two genetic lineages and frequent reassortment between wild-type strains. J. Gen. Virol. 2009; 90: 1923 – 1931.Богданова С., Гавриловская И., Бойко В. и др. Персистирующая инфекция, вызванная вирусом ГЛПС у рыжих полёвок-природных хозяев вируса. Микробиол. Журнал. 1987; 49 (4): 99 - 106.Bogdanova С., Gavrilovskaya I.N., Boyko V. et al. Persestiruyuchay infection, caused by HFRS virus in bank voles – natural house of virus. Mikrobiol. Zhurnal [Microbiology Journal]. 1987; 49 (4): 99 – 106 (in Russia).Enria D., Padula Fi, Segura E.L., Pini N., Edelstein A., Riva Posse C. Hantavirus pulmonary syndrome in Argentina. Possibility of person to person transmission. Medicina (B Aires). 1996; 56 (6): 709 - 711.Enria D., Padula P., Segura E.L., Pini N., Edelstein A., Riva Posse C. Hantavirus pulmonary syndrome in Argentina. Possibility of person to person transmission. Medicina (B Aires). 1996; 56 (6): 709 – 711.Gavrilovskaya I.N., Brown E.J., Ginsberg M.H., Mackow E.R. Cellular entry of hantaviruses which cause hemorrhagic fever with renal syndrome is mediated by beta3 integrins. J. Virol. 1999; 73 (5):3951 - 3959.Gavrilovskaya I.N., Brown E.J., Ginsberg M.H., Mackow E.R.. Cellular entry of hantaviruses which cause hemorrhagic fever with renal syndrome is mediated by beta3 integrins. J. Virol. 1999; 73 (5):3951 – 3959.Mackow E.R., Gavrilovskaya I.N. Hantavirus regulation of endothelial cell functions. Thromb. Haemost. 2009; 102 (6): 1030 - 1034.Mackow E.R., Gavrilovskaya I.N. Hantavirus regulation of endothelial cell functions. Thromb. Haemost. 2009; 102 (6): 1030 – 1034.Geimonen E., Neff S., Raymond T., Kocer S.S., Gavrilovskaya.IN., Mackow E.R. Pathogenic and nonpathogenic hantaviruses differentially regulate endothelial cell responses. Proc. Natl. Acad. Sci. USA. 2002; 99: 13837 - 13842.Geimonen E., Neff S., Raymond T., Kocer S.S., Gavrilovskaya .IN., Mackow E.R. Pathogenic and nonpathogenic hantaviruses differentially regulate endothelial cell responses. Proc. Natl. Acad. Sci. USA. 2002; 99: 13837 – 13842.Gorbunova E., Gavrilovskaya I.N., Mackow E.R. Pathogenic Hantaviruses Andes virus and Hantaan virus induce adherens junction disassembly by directing vascular endothelial cadherin internalization in human endothelial cells. Virol. 2010; 84 (14): 7405 - 7411.Gorbunova E., Gavrilovskaya I.N., Mackow E.R. Pathogenic Hantaviruses Andes virus and Hantaan virus induce adherens junction disassembly by directing vascular endothelial cadherin internalization in human endothelial cells. Virol. 2010; 84 (14): 7405 – 7411.Gavrilovskaya I.N., Gorbunova E.E., Mackow N.A., Mackow E.R. Hantaviruses direct endothelial cell permeability by sensitizing cells to the vascular permeability factor VEGF, while angiopoietin 1 and sphingosine 1-phosphate inhibit hantavirus-directed permeability. J. Virol. 2008; 82 (12): 5797 - 5806.Gavrilovskaya I.N., Gorbunova E.E., Mackow N.A., Mackow E.R. Hantaviruses direct endothelial cell permeability by sensitizing cells to the vascular permeability factor VEGF, while angiopoietin 1 and sphingosine 1-phosphate inhibit hantavirus- directed permeability. J. Virol. 2008; 82 (12): 5797 – 5806.Vaheri A., Strandin T., Hepojoki J., Sironen T., Henttonen H., M kel S., Mustonen J. Uncovering the mysteries of hantavirus infections. Microbiology. 2013; 11: 539 - 550.Vaheri A., Strandin T., Hepojoki J., Sironen T., Henttonen H., Mäkelä S., Mustonen J. Uncovering the mysteries of hantavirus infections. Microbiology. 2013; 11: 539 – 550.Lundkvist A., Kallio-Kokko H., Sjolander K.B. Lankinen H., Niklasson B., Vaheri A. et al. Characterization of Puumala virus nucleocapsid protein: identi cation of B-cell epitopes and domains involved in protective immunity. Virology. 1996; 216 (2): 397 - 406.Lundkvist A., Kallio-Kokko H., Sjolander K.B. Lankinen H., Niklasson B., Vaheri A. et al. Characterization of Puumala virus nucleocapsid protein: identification of B-cell epitopes and domains involved in protective immunity. Virology. 1996; 216 (2): 397 – 406.Maes P, Keyaerts E, Bonnet V et al. Truncated recombinant Dobrava hantavirus nucleocapsid proteins induce strong, long-lasting immune responses in mice. Intervirology. 2006; 49 (5): 253 - 260.Maes P, Keyaerts E, Bonnet V et al. Truncated recombinant Dobrava hantavirus nucleocapsid proteins induce strong, long-lasting immune responses in mice. Intervirology. 2006; 49 (5): 253 – 260.Lundkvist A, Horling J, Niklasson B. The humoral response to Puumala virus infection (nephropathia epidemica) investigated by viral protein speci c immunoassays. Arch. Virol. 1993; 130 (1 - 2): 121 - 130.Lundkvist A, Horling J, Niklasson B. The humoral response to Puumala virus infection (nephropathia epidemica) investigated by viral protein specific immunoassays. Arch. Virol. 1993; 130 (1 – 2): 121 – 130.Alexeyev O.A., Ahlm C., Billheden J., Settergren B., Wadell G., Juto P. Elevated levels of total and Puumala virus-specific immunoglobulin E in the Scandinavian type of hemorrhagic fever with renal syndrome. Clin Diagn Lab Immunol. 1994; 1 (3): 269 - 272.Alexeyev O.A., Ahlm C., Billheden J., Settergren B., Wadell G., Juto P. Elevated levels of total and Puumala virus-specific immunoglobulin E in the Scandinavian type of hemorrhagic fever with renal syndrome. Clin Diagn Lab Immunol. 1994; 1 (3): 269 – 272.Van Epps, H.L., Terajima M., Mustonen J., Arstila T.P, Corey E.A., Vaheri A., Ennis F.A. Long-lived memory T lymphocyte responses after hantavirus infection. J Exp Med. 2002; 196 (5): 579 - 588Van Epps, H.L., Terajima M., Mustonen J., Arstila T.P., Corey E.A., Vaheri A., Ennis F.A. Long-lived memory T lymphocyte responses after hantavirus infection. J Exp Med. 2002; 196 (5): 579 – 588Terajima M., Van Epps H.L., Li D., Leporati A.M., Juhlin S.E., Mustonen J., Vaheri A. Generation of recombinant vaccinia viruses expressing Puumala virus proteins and use in isolating cytotoxic T cells specific for Puumala virus. Virus Res. 2002; 84 (1 - 2): 67 - 77Terajima M., Van Epps H.L., Li D., Leporati A.M., Juhlin S.E., Mustonen J., Vaheri A. Generation of recombinant vaccinia viruses expressing Puumala virus proteins and use in isolating cytotoxic T cells specific for Puumala virus. Virus Res. 2002; 84 (1 – 2): 67 – 77.

The authors declare that there are no conflicts of interest present.