American Journal of Infectious Diseases and Microbiology
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American Journal of Infectious Diseases and Microbiology. 2015, 3(2), 77-86
DOI: 10.12691/ajidm-3-2-4
Open AccessReview Article

Effects of Anthropogenic Events and Viral Persistence on Rodent Reservoirs of Hantavirus Infection: Understanding Host-Pathogen Interactions Facilitates Novel Approaches to Intervention Strategies

Abdullah Mahmud-Al-Rafat1, 2, Mahbub -E-Sobhani1 and Andrew W. Taylor-Robinson3,

1Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna, Bangladesh

2Research and Development Department (R&D), Incepta Vaccine Limited. Dewan Idris Road, Jirabo, Savar Dhaka, Bangladesh

3School of Medical & Applied Sciences, Central Queensland University, Rockhampton, Australia

Pub. Date: April 12, 2015

Cite this paper:
Abdullah Mahmud-Al-Rafat, Mahbub -E-Sobhani and Andrew W. Taylor-Robinson. Effects of Anthropogenic Events and Viral Persistence on Rodent Reservoirs of Hantavirus Infection: Understanding Host-Pathogen Interactions Facilitates Novel Approaches to Intervention Strategies. American Journal of Infectious Diseases and Microbiology. 2015; 3(2):77-86. doi: 10.12691/ajidm-3-2-4

Abstract

Hantaviruses are primarily rodent-borne pathogens which have received considerable attention recently due to their high mortality rates in humans. In order to find the causes of rapid transmission and emergence of hantavirus-associated diseases anthropogenic changes are a priority. These include deforestation, urbanization, noise pollution, light pollution and electromagnetic fields, all of which have been shown to profoundly affect rodent physiology and immunology. Moreover, anthropogenic events promote human-rodent co-habitation and thereby provide a driver to increase rates of transmission and, by extrapolation, levels of infection in humans. Such environmental disruption acts as a chronic stressor to rodents and causes elevated concentrations of glucocorticoids, which are a major class of immunosuppressive hormone. Glucocorticoids are responsible for altering the immune tolerance of rodents, thereby rendering them susceptible to infection. Glucocorticoids induce regulatory T lymphocytes to reduce inflammatory and antiviral responses and to activate regulatory responses, principally through production of the cytokines interleukin-10 and transforming growth factor-β to support viral persistence. In order to develop a low-cost intervention strategy for hantavirus infection consideration should be given to a systemic approach to therapy. This would both aim to achieve a reduction of anthropogenic stressors and to gain a greater understanding of host-pathogen interactions.

Keywords:
hantavirus rodent reservoir viral persistence anthropogenic event glucocorticoid regulatory T lymphocyte anti-viral

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References:

[1]  van Doom HR. (2014). Emerging infectious diseases. Medicine 42, 60-63.
 
[2]  Epstein PR. (1995). Emerging diseases and ecosystem instability: new threats to public health. Am J Public Health 85, 168-172.
 
[3]  Rhyan JC, Spraker TR. (2010). Emergence of diseases from wildlife reservoirs. Vet Pathol 47, 34-39.
 
[4]  Lee HW, Lee PW, Johnson KM. (1978). Isolation of the etiologic agent of Korean hemorrhagic fever. J Infect Dis 137, 298-308.
 
[5]  Mills JN. (2006). Biodiversity loss and emerging infectious disease: An example from the rodent-borne hemorrhagic fevers. Biodiversity 7, 9-17.
 
[6]  Ulrich R, Hjelle B, Pitra C, Krüger DH. (2002). Emerging viruses: the case ‘hantavirus’. Intervirology 45, 318-327.
 
[7]  Maes P, Clement J, Gavrilovskaya I, Van Ranst M. (2004). Hantaviruses: immunology, treatment, and prevention. Viral Immunol 17, 481-497.
 
[8]  Jonsson CB, Figueiredo LT, Vapalahti O. (2010). A global perspective on Hantavirus ecology, epidemiology, and disease. Clin Microbiol Rev 23, 412-441.
 
[9]  Clement J, Vercauteren J, Verstraeten WW, Ducoffre G, Barrios JM, Vandamme AM, Maes P, Van Ranst M. (2009). Relating increasing hantavirus incidences to the changing climate: the mast connection. Int J Health Geogr 8, 1.
 
[10]  Daszak P, Cunningham AA, Hyatt AD. (2001). Anthropogenic environmental change and the emergence of infectious diseases in wildlife. Acta Trop 78, 103-116.
 
[11]  Martin LB, Weil ZM, Nelson RJ. (2008). Seasonal changes in vertebrate immune activity: mediation by physiological trade-offs. Philos Trans R Soc Lond B Biol Sci 363, 321-339.
 
[12]  McCabe PM, Sheridan JF, Weiss JM, Kaplan JP, Natelson BH, Pare WP. (2000). Animal models of disease. Physiol Behav 68, 501-507.
 
[13]  Dickens MJ, Delehanty DJ, Romero LM. (2010). Stress: an inevitable component of animal translocation. Biol Cons 143, 1329-1341.
 
[14]  Martin LB, Andreassi E, Watson W, Coon C. (2011). Stress and animal health: physiological mechanisms and ecological consequences. Nat Educ Knowl 3, 11.
 
[15]  Al-Rafat AM, Taylor-Robinson AW. (2014). Emergence and persistence of hantavirus in rodent reservoirs: role of glucocorticoid hormone. Immun Dis 2, a9.
 
[16]  Easterbrook JD, Zink MC, Klein SL. (2007). Regulatory T cells enhance persistence of the zoonotic pathogen Seoul virus in its reservoir host. Proc Natl Acad Sci USA 104, 15502-15507.
 
[17]  Stary G, Klein I, Bauer W, Koszik F, Reininger B, Kohlhofer S, Gruber K, Skvara H, Jung T, Stingl G. (2011). Glucocorticosteroids modify Langerhans cells to produce TGF- and expand regulatory T cells. J Immunol 186, 103-112.
 
[18]  Nichol ST, Beaty BJ, Elliott RM, Goldbach R, Plyusnin A, Schmaljohn CS, Tesh RB. (2005). Bunyaviridae. In: Virus Taxonomy, 8th edn. Eighth Report of the International Committee on Taxonomy of Viruses (Amsterdam: Elsevier).
 
[19]  Watson DC, Sargianou M, Papa A, Chra P, Starakis I, Panos G. (2013). Epidemiology of Hantavirus infections in humans: a comprehensive, global overview. Crit Rev Microbiol 40, 261-272.
 
[20]  Zöller L, Faulde M, Meisel H, Ruh B, Kimmig P, Schelling U, Zeier M, Kulzer P, Becker C, Roggendorf M, Bautz EKF, Krüger DH, Darai G. (1995). Seroprevalence of hantavirus antibodies in Germany as determined by a new recombinant enzyme immunoassay. Eur J Clin Microbiol Infect Dis 14, 305-313.
 
[21]  Deutz A, Fuchs K, Schuller W, Nowotny N, Auer H, Aspock H, Stunzner D, Kerbl U, Klement C, Kofer J. (2003). Seroepidemiological studies of zoonotic infections in hunters in southeastern Austria - prevalences, risk factors, and preventive methods. Berl Munch Tierarztl Wochenschr 116, 306-311.
 
[22]  Hardestam J, Karlsson M, Falk KI, Olsson G, Klingström J, Lundkvist A. (2008). Puumala Hantavirus excretion kinetics in bank voles (Myodes glareolus). Emerg Infect Dis 14, 1209-1215.
 
[23]  Wells RM, Sosa Estani S, Yadon ZE, Enria D, Padula P, Pini N, Mills JN, Peters CJ, Segura EL. (1997). An unusual hantavirus outbreak in southern Argentina: person-to-person transmission? Hantavirus Pulmonary Syndrome Study Group for Patagonia. Emerg Infect Dis 3, 171-174.
 
[24]  Ftika L, Maltezou HC. (2013). Viral haemorrhagic fevers in healthcare settings. J Hosp Infect 83, 185-192.
 
[25]  25.Childs JE, Krebs JW, Ksiazek TG, Maupin GO, Gage KL, Rollin PE, Zeitz PS, Sarisky J, Enscore RE, Butler JC, Cheek JE, Glass GE, Peters CJ. (1995). A household-based, casecontrol study of environmental factors associated with Hantavirus pulmonary syndrome in the southwestern United States. Am J Trop Med Hyg 52, 393-397.
 
[26]  Crowcroft NS, Infuso A, Ilef D, Le Guenno B, Desenclos JC, Van Loock F, Clement J. (1999). Risk factors for human Hantavirus infection: Franco-Belgian collaborative case-control study during 1995-96 epidemic. Brit Med J 318, 1737-1738.
 
[27]  Winter CH, Brockmann SO, Piechotowski I, Alpers K, an der Heiden M, Koch J, Stark K, Pfaff G. (2009). Survey and case control study during epidemics of Puumala virus infection. Epidemiol Infect 137, 1479-1485.
 
[28]  Van Loock F, Thomas I, Clement J, Ghoos S, Colson P. (1999). A case-control study after a Hantavirus infection outbreak in the south of Belgium: who is at risk? Clin Infect Dis 28, 834-839.
 
[29]  Mulic´ R, Ropac D. (2002). Epidemiologic characteristics and military implications of hemorrhagic fever with renal syndrome in croatia. Croat Med J 43, 581-586.
 
[30]  Tkachenko EA, Dzagurova TK, Bernshtein AD, Morozov VG, Slonova RA, Ivanov LI, Trankvilevskiĭ DV, Kruger D. (2010). Hemorrhagic fever with renal syndrome in Russia in 21st century. In: VIII International Conference on HFRS, HPS and Hantavirus (Athens, Greece), p. 27 (abstract).
 
[31]  Zhang Y, Zou Y, Fu Z, Plyusnin A. (2010). Hantavirus infections in humans and animals, China. Emerg Infect Dis 16, 1195-1203.
 
[32]  Suzán G, Marcé E, Giermakowski JT, Mills JN, Ceballos G, Ostfeld RS, Armién B, Pascale JM, Yates TL. (2009). Experimental evidence for reduced rodent diversity causing increased Hantavirus prevalence. PLoS ONE 4, e5461.
 
[33]  Plyusnin A, Morzunov SP. (2001). Virus evolution and genetic diversity of hantaviruses and their rodent hosts. Curr Top Microbiol Immunol 256, 47-75.
 
[34]  Plyusnin A. (2002). Genetics of hantaviruses: implications to taxonomy. Arch Virol 147, 665-682.
 
[35]  Kang HJ, Bennett SN, Dizney L, Sumibcay L, Arai S, Ruedas LA, Song JW, Yanagihara R. (2009). Host switch during evolution of a genetically distinct hantavirus in the American shrew mole (Neurotrichus gibbsii). Virology 388, 8-14.
 
[36]  Arai S, Ohdachi SD, Asakawa M, Kang HJ, Mocz G, Arikawa J, Okabe N, Yanagihara R. (2008). Molecular phylogeny of a newfound hantavirus in the Japanese shrew mole (Urotrichus talpoides). Proc Natl Acad Sci USA 105, 16296-16301.
 
[37]  Arai S, Bennett SN, Sumibcay L, Cook JA, Song J-W, Hope A, Parmenter C, Nerurkar VR, Yates TL, Yanagihara R. (2008). Phylogenetically distinct hantaviruses in the masked shrew (Sorex cinereus) and dusky shrew (Sorex monitcolus) in the United States. Am J Trop Med Hyg 78, 348-351.
 
[38]  Kang HJ, Bennett SN, Sumibcay L, Arai S, Hope AG, Mocz G, Song JW, Cook JA, Yanagihara R. (2009). Evolutionary insights from a genetically divergent Hantavirus harbored by the European common mole (Talpa europaea). PLoS ONE 4, e6149.
 
[39]  Yanagihara R, Gu SH, Arai S, Kang HJ, Song JW. (2014). Hantaviruses: rediscovery and new beginnings. Virus Res 187, 6-14.
 
[40]  Ramsden C, Holmes EC, Charleston MA. (2009). Hantavirus evolution in relation to its rodent and insectivore hosts: no evidence for codivergence. Mol Biol Evol 26, 143-153.
 
[41]  Vapalahti O, Lundkvist A, Fedorov V, Conroy CJ, Hirvonen S, Plyusnina A, Nemirov K, Fredga K, Cook JA, Niemimaa J, Kaikusalo A, Henttonen H, Vaheri A, Plyusnin A. (1999). Isolation and characterization of a Hantavirus from Lemmus sibiricus: evidence for host switch during Hantavirus evolution. J Virol 73, 5586-5592.
 
[42]  Nichol ST, Spiropoulou CF, Morzunov S, Rollin PE, Ksiazek TG, Feldmann H, Sanchez A, Childs J, Zaki S, Peters CJ. (1993). Genetic identification of a novel hantavirus associated with an outbreak of acute respiratory illness in the southwestern United States. Science 262, 914-917.
 
[43]  Schönrich G, Rang A, Lütteke N, Raftery MJ, Charbonnel N, Ulrich RG. (2008). Hantavirus-induced immunity in rodent reservoirs and humans. Immunol Rev 225, 163-189.
 
[44]  Muranyi W, Bahr U, Zeier M, van der Woude FJ. (2005). Hantavirus infection. J Am Soc Nephrol 16, 3669-3679.
 
[45]  Sirotin BZ, Keiser NP. (2001). On the history of the study of haemorrhagic fever with renal syndrome in eastern Russia. Nephrol Dial Transplant 16, 1288-1289.
 
[46]  Beers MH, Berkow R. (2005). Infectious diseases; viral diseases. In: The Merck Manual of Diagnosis and Therapy, 17th edn (Indianapolis: Wiley Publishers).
 
[47]  McCabe PM, Sheridan JF, Weiss JM, Kaplan JP, Natelson BH, Pare WP. (2000). Animal models of disease. Physiol Behav 68, 501-507.
 
[48]  Faeth SH, Warren PS, Shochat E, Marussich WA. (2005). Trophic dynamics in urban communities. Bioscience 55, 399-407.
 
[49]  Shochat E, Warren PS, Faeth SH, McIntyre NE, Hope D. (2006). From patterns to emerging processes in mechanistic urban ecology. Trends Ecol Evol 21, 186-191.
 
[50]  Mackelprang R, Dearing MD, St. Jeor S. (2001). High prevalence of Sin Nombre Virus in rodent populations, central Utah: a consequence of human disturbance? Emerg Infect Dis 7, 480-482.
 
[51]  Goodin DG, Koch DE, Owen RD, Chu Y-K, Hutchinson JMS, Jonsson CB. (2006). Land cover associated with hantavirus presence in Paraguay. Glob Ecol Biogeogr 15, 519-527.
 
[52]  Bradley CA, Altizer S. (2006). Urbanization and the ecology of wildlife diseases. Trends Ecol Evol 22, 95-102.
 
[53]  Pergams ORW, Lawler JJ. (2009). Recent and widespread rapid morphological change in rodents. PLoS ONE 4, e6452.
 
[54]  Baldwin AL. (2007). Effects of noise on rodent physiology. Int J Comp Psychol 20, 134-144.
 
[55]  Wright AJ, Soto AG, Baldwin AL, Bateson M, Beale CM, Clark C, Deak T, Edwards EF, Fernández A, Godinho A, Hatch L, Kakuschke A, Lusseau D, Martineau D, Romero LM, Wintle B, Weilgart L, Notarbartolo-di-Sciara G, Martin V. (2007). Anthropogenic noise as a stressor in animals: a multidisciplinary perspective. Int J Comp Psychol 20, 250-273.
 
[56]  Kight CR, Swaddle JP. (2011). How and why environmental noise impacts animals: an integrative, mechanistic review. Ecol Lett 14, 1052-1061.
 
[57]  Fonken LK, Finy MS, Walton JC, Weil ZM, Workman JL, Ross J, Nelson RJ. (2009). Influence of light at night on murine anxiety- and depressive-like responses. Behav Brain Res 205, 349-354.
 
[58]  Kyba CCM, Ruhtz T, Fischer J, Hölker F. (2011). Cloud coverage acts as an amplifier for ecological light pollution in urban ecosystems. PLoS ONE 6, e17307.
 
[59]  Ikeda M, Sagara M, Inoue S. (2000). Continuous exposure to dim illumination uncouples temporal patterns of sleep, body temperature, locomotion and drinking behavior in the rat. Neurosci Lett 279, 185-189.
 
[60]  Navara KJ, Nelson RJ. (2007). The dark side of light at night: physiological, epidemiological, and ecological consequences. J Pineal Res 43, 215-224.
 
[61]  Bedrosian TA, Fonken LK, Walton JC, Nelson RJ. (2011). Chronic exposure to dim light at night suppresses immune responses in Siberian hamsters. Biol Lett 7, 468-471.
 
[62]  Meerlo P, Koehl M, van der Borght K, Turek FW. (2002). Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress. J Neuroendocrinol 14, 397-402.
 
[63]  Baydaş G, Erçel E, Canatan H, Dönder E, Akyol A. (2001). Effect of melatonin on oxidative status of rat brain, liver, and kidney tissues under constant light exposure. Cell Biochem Funct 19, 37-41.
 
[64]  Abílio VC, Freitas FM, Dolnikoff MS, Castrucci AM, Frussa-Filho R. (1999). Effects of continuous exposure to light on behavioral dopaminergic supersensitivity. Biol Psychiatry 45, 1622-1629.
 
[65]  Van der Meer E, Van Lool PL, Baumans V. (2004). Short-term effects of a disturbed light-dark cycle and environmental enrichment on aggression and stress-related parameters in male mice. Lab Animal 38, 376-383.
 
[66]  Hardell L, Holmberg B, Malker H, Paulsson LE. (1995). Exposure to extremely low frequency electromagnetic fields and the risk of malignant diseases an evaluation of epidemiological and experimental findings. Eur J Cancer Prevent 4, Suppl 1, 3-107.
 
[67]  Portier CJ, Wolfe MS. (1998). Assessment of health effects from exposure to power-line frequency electric and magnetic fields. NIEHS Working Group Report, North Carolina, Research Triangle Park.
 
[68]  Lindgren M, Gustavsson M, Hamnerius Y, Galt S. (2001). ELF magnetic fields in a city environment. Bioelectromagnetics 22, 87-90.
 
[69]  Bruyn de L, Jager de L. (1994). Electric field exposure and evidence of stress in mice. Environ Res 65, 149-160.
 
[70]  Mostafa RM, Mostafa YM, Ennaceur A. (2002). Effects of exposure to extremely low frequency magnetic field of 2 G intensity on memory and corticosterone level in rats. Physiol Behav 76, 589-595.
 
[71]  Szemerszky R, Zelena D, Barna I, Bárdos G. (2010). Stress-related endocrinological and psychopathological effects of short- and long-term 50 Hz electromagnetic field exposure in rats. Brain Res Bull 81, 92-99.
 
[72]  Prochnow N, Gebing T, Ladage K, Krause-Finkeldey D, El Ouardi A, Bitz A, Streckert J, Hansen V, Dermietzel R. (2011). Electromagnetic field effect or simply stress? Effects of UMTS exposure on hippocampal longterm plasticity in the context of procedure related hormone release. PLoS ONE 6, e19437.
 
[73]  Li M, Wang Y, Zhang Y, Zhou Z, Yu Z. (2008). Elevation of plasma corticosterone levels and hippocampal receptor translocation in rats: a potential mechanism for cognition impairment following chronic low-power-density microwave exposure. J Radiat Res 49, 163-170.
 
[74]  Batuman OA, Sajewski D, Ottenweller JE, Pitman Dl, Natelson BH. (1990). Effects of repeated stress on T cell numbers and function in rats. Brain Behav Immun 4, 105-117.
 
[75]  75.Dhabhar FS, Miller AH, McEwen BS, Spencer RL. (1995). Effects of stress on immune cell distribution. Dynamics and hormonal mechanisms. J Immunol 154, 5511-5527.
 
[76]  Romero LM, Butler LK. (2007). Endocrinology of stress. Int J Comp Psychol 20, 89-95.
 
[77]  Busch DS, Hayward LS. (2009). Stress in a conservation context: a discussion of glucocorticoid actions and how levels change with conservation-relevant variables. Biol Cons 142, 2844-2853.
 
[78]  Råberg L, Graham AL, Read AF. (2009). Decomposing health: tolerance and resistance to parasites in animals. Philos Trans R Soc Lond B Biol Sci 364, 37-49.
 
[79]  Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. (2008). From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9, 46-57.
 
[80]  Martin LB, Hopkins WA, Mydlarz LD, Rohr JR. (2010). The effects of anthropogenic global changes on immune functions and disease resistance. Ann NY Acad Sci 1195, 129-148.
 
[81]  Padgett DA, Glaser R. (2003). How stress influences the immune respon. Trends Immunol 24, 444-448.
 
[82]  Firth C, Bhat M, Firth MA, Williams SH, Frye MJ, Simmonds P, Conte JM, Ng J, Garcia J, Bhuva NP, Lee B, Che X, Quan P-L, Lipkin WI. (2014). Detection of zoonotic pathogens and characterization of novel viruses carried by commensal Rattus norvegicus in New York City. mBio 5:e01933-14.
 
[83]  Hilleman MR. (2004). Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections. Proc Natl Acad Sci USA 101, 14560-14566.
 
[84]  Easterbrook JD, Klein SL (2008). Immunological mechanisms mediating hantavirus persistence in rodent reservoirs. PLoS Pathog 4, e1000172.
 
[85]  Hannah MF, Bajic VB, Klein SL (2008). Sex differences in the recognition of and innate antiviral responses to Seoul virus in Norway rats. Brain Behav Immun 22, 503-516.
 
[86]  Geimonen E, Neff S, Raymond T, Kocer SS, Gavrilovskaya IN, Mackow ER. (2002). Pathogenic and nonpathogenic hantaviruses differentially regulate endothelial cell responses. Proc Natl Acad Sci USA 99, 13837-13842.
 
[87]  Kraus AA, Raftery MJ, Giese T, Ulrich R, Zawatzky R, Hippenstiel S, Suttorp N, Kruger DH, Schonrich G. (2004). Differential antiviral response of endothelial cells after infection with pathogenic and nonpathogenic hantaviruses. J Virol 78, 6143-6150.
 
[88]  Easterbrook JD, Klein SL. (2008). Corticosteroids modulate Seoul virus infection, regulatory T-cell responses and matrix metalloprotease 9 expression in male, but not female, Norway rats. J Gen Virol 89, 2723-2730.
 
[89]  Klein SL, Bird BH, Glass GE. (2000). Sex differences in Seoul virus infection are not related to adult sex steroid concentrations in Norway rats. J Virol 74, 8213-8217.
 
[90]  Jin HK, Yoshimatsu K, Takada A, Ogino M, Asano A, Arikawa J, Watanabe T. (2001). Mouse Mx2 protein inhibits hantavirus but not influenza virus replication. Arch Virol 146, 41-49.
 
[91]  Dohmae K, Okabe M, Nishimune Y. (1994). Experimental transmission of hantavirus infection in laboratory rats. J Infect Dis 170, 1589-1592.
 
[92]  Araki K, Yoshimatsu K, Lee BH, Kariwa H, Takashima I, Arikawa J. (2004). A new model of Hantaan virus persistence in mice: the balance between HTNV infection and CD8+ T-cell responses. Virology 322, 318-327.
 
[93]  Belkaid Y. (2007). Regulatory T cells and infection: a dangerous necessity. Nat Rev Immunol 7, 875-888.
 
[94]  Schountz T, Prescott J. (2014). Hantavirus immunology of rodent reservoirs: current status and future directions. Viruses 6, 1317-1335.
 
[95]  Schountz T, Prescott J, Cogswell AC, Oko L, Mirowsky-Garcia K, Galvez AP, Hjelle B. (2007). Regulatory T cell-like responses in deer mice persistently infected with Sin Nombre virus. Proc Natl Acad Sci USA 104, 15496-15501.
 
[96]  Mosmann TR, Coffman RL. (1989). TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7, 145-173.
 
[97]  Farrar JD, Ouyang W, Lohning M, Assenmacher M, Radbruch A, Kanagawa O, Murphy KM. (2001). An instructive component in T helper cell type 2 (Th2) development mediated by GATA-3. J Exp Med 193, 643-650.
 
[98]  Campbell DJ, Ziegler SF. (2007). FOXP3 modifies the phenotypic and functional properties of regulatory T cells. Nat Rev Immunol 7, 305-310.
 
[99]  Zhao DM, Thornton AM, DiPaolo RJ, Shevach EM. (2006). Activated CD4+CD25+ T cells selectively kill B lymphocytes. Blood 107, 3925-3932.
 
[100]  Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T. (2009). Regulatory T cells: how do they suppress immune responses? Int Immunol 21, 1105-1111.
 
[101]  Raftery MJ, Kraus AA, Ulrich R, Krüger DH, Schönrich G. (2002). Hantavirus infection of dendritic cells. J Virol 76, 10724-10733.
 
[102]  Botten J, Mirowsky K, Kusewitt D, Ye C, Gottlieb K, Prescott J, Hjelle B. (2003). Persistent Sin Nombre virus infection in the deer mouse (Peromyscus maniculatus) model: sites of replication and strand-specific expression. J Virol 77, 1540-1550.
 
[103]  Borucki MK, Boone JD, Rowe JE, Bohlman MC, Kuhn EA, DeBaca R, St Jeor SC. (2000). Role of maternal antibody in natural infection of Peromyscus maniculatus with Sin Nombre virus. J Virol 74, 2426-2429.
 
[104]  Kallio ER, Poikonen A, Vaheri A, Vapalahti O, Henttonen H, Koskela E, Mappes T. (2006). Maternal antibodies postpone hantavirus infection and enhance individual breeding success. Proc Biol Soc 273, 2771-2776.
 
[105]  Ashwell JD, Lu FW, Vacchio MS. (2000). Glucocorticoids in T cell development and function. Annu Rev Immunol 18, 309-345.
 
[106]  Refojo D, Liberman AC, Holsboer F, Arzt E. (2001). Transcription factormediated molecular mechanisms involved in the functional cross-talk between cytokines and glucocorticoids. Immunol Cell Biol 79, 385-394.
 
[107]  Rhen T, Cidlowski JA. (2005). Antiinflammatory action of glucocorticoids - new mechanisms for old drugs. N Engl J Med 353, 1711-1723.
 
[108]  Rutella S, Danese S, Leone G. (2006). Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 108, 1435-1440.
 
[109]  Sternberg EM. (2006). Neural regulation of innate immunity: A coordinated nonspecific host response to pathogens. Nat Rev Immunol 6, 318-328.
 
[110]  Baschant U, Tuckermann J. (2010). The role of the glucocorticoid receptor in inflammation and immunity. J Steroid Biochem Mol Biol 120, 69-75.
 
[111]  Ahsan MR, Al-Rafat AM, Sobhani ME, Molla MAW. (2013). Biomolecular basis of the role of chronic psychological stress hormone ‘‘glucocorticoid’’ in alteration of cellular immunity during cancer. Memo - Magazine of European Medical Oncology 6, 127-136.
 
[112]  Ramírez F, Fowell DJ, Puklavec M, Simmonds S, Mason D. (1996). Glucocorticoids promote a TH2 cytokine response by CD4+ T cells in vitro. J Immunol 156, 2406-2412.
 
[113]  Gratchev A, Kzhyshkowska J, Utikal J, Goerdt S. (2005). Interleukin-4 and dexamethasone counterregulate extracellular matrix remodelling and phagocytosis in type-2 macrophages. Scand J Immunol 61, 10-17.
 
[114]  Bailey MT, Avitsur R, Engler H, Padgett DA, Sheridan JF. (2004). Physical defeat reduces the sensitivity of murine splenocytes to the suppressive effects of corticosterone. Brain Behav Immun 18, 416-424.
 
[115]  Gratchev A, Kzhyshkowska J, Kannookadan S, Ochsenreiter M, Popova A, Yu X, Mamidi S, Stonehouse-Usselmann E, Muller-Molinet I, Gooi LM, Goerdt S. (2008). Activation of a TGF-β specific multistep gene expression program in mature macrophages requires glucocorticoid-mediated surface expression of TGF-β receptor II. J Immunol 180, 6553-6565.
 
[116]  Ruzek MC, Pearce BD, Miller AH, Biron CA. (1999). Endogenous glucocorticoids protect against cytokine-mediated lethality during viral infection. J Immunol 162, 3527-3533.
 
[117]  Bailey M, Engler H, Hunzeker J, Sheridan JF. (2003). The hypothalamic-pituitary-adrenal axis and viral infection. Viral Immunol 16, 141-157.
 
[118]  Huggins JW, Kim GR, Brand OM, McKee KT Jr. (1986). Ribavirin therapy for Hantaan virus infection in suckling mice. J Infect Dis 153, 489-497.
 
[119]  Huggins JW, Hsiang CM, Cosgriff TM, Guang MY, Smith JI, Wu ZO, LeDuc JW, Zheng ZM, Meegan JM, Wang QN, Oland DD, Gui XE, Gibbs PH, Yuan GH, Zhang TM. (1991). Prospective, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin therapy of hemorrhagic fever with renal syndrome. J Infect Dis 164, 1119-1127.
 
[120]  Severson WE, Schmaljohn CS, Javadian A, Jonsson CB. (2003). Ribavirin causes error catastrophe during Hantaan virus replication. J Virol 77, 481-488.
 
[121]  Chapman LE, Mertz GJ, Peters CJ, Jolson HM, Khan AS, Ksiazek TG, Koster FT, Baum KF, Rollin PE, Pavia AT, Holman RC, Christenson JC, Rubin PJ, Behrman RE, Bell LJ, Simpson GL, Sadek RF. (1999). Ribavirin Study Group: intravenous ribavirin for hantavirus pulmonary syndrome. Safety and tolerance during 1 year of open-label experience. Antivir Ther 4, 211-219.
 
[122]  Chapman LE, Ellis BA, Koster FT, Sotir M, Ksiazek TG, Mertz GJ, Rollin PE, Baum KF, Pavia AT, Christenson JC, Rubin PJ, Jolson HM, Behrman RE, Khan AS, Bell LJ, Simpson GL, Hawk J, Holman RC, Peters CJ. (2002). Ribavirin Study Group: discriminators between hantavirus-infected and -uninfected persons enrolled in a trial of intravenous ribavirin for presumptive hantavirus pulmonary syndrome. Clin Infect Dis 34, 293-304.
 
[123]  Vapalahti K, Virtala A, Vaheri A, Vapalahti O. (2010). Case-control study on Puumala virus infection: smoking is a risk factor. Epidemiol Infect 138, 576-584.
 
[124]  Piyasirisilp S, Schmeckpeper BJ, Chandanayingyong D, Hemachudha T, Griffin DE. (1999). Association of HLA and T-cell receptor gene polymorphisms with Semple rabies vaccine-induced autoimmune encephalomyelitis. Ann Neurol 45, 595-600.
 
[125]  Park K, Kim CS, Moon KT. (2004). Protective effectiveness of hantavirus vaccine. Emerg Infect Dis 10, 2218-2220.
 
[126]  .Schmaljohn C. (2009). Vaccines for hantaviruses. Vaccine 27, Suppl 4, D61-D64.
 
[127]  Chu YK, Jennings GB, Schmaljohn CS. (1995). A vaccinia virus-vectored Hantaan virus vaccine protects hamsters from challenge with Hantaan and Seoul viruses but not Puumala virus. J Virol 69, 6417-6423.
 
[128]  Hooper JW, Custer DM, Thompson E, Schmaljohn CS. (2001). DNA vaccination with the Hantaan virus M gene protects hamsters against three of four HFRS hantaviruses and elicits a high-titer neutralizing antibody response in Rhesus monkeys. J Virol 75, 8469-8477.
 
[129]  Hammerbeck CD, Hooper JW. (2010). Hantavirus vaccines. In: New Generation Vaccines, MM Levine, ed. (New York: Informa Healthcare), pp. 905-913.
 
[130]  Hooper JW, Josleyna M, Ballantyneb J, Brocato R. (2013). 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). Vaccine 31, 4314- 4321.
 
[131]  Akhmatova NK, Yusupova RS, Khaiboullina SF, Sibiryak SV (2003). Lymphocyte apoptosis during hemorrhagic fever with renal syndrome. Russian J Immunol 8, 37-46.