Jonas Klingström group - Understanding the mechanisms behind hantavirus-mediated pathogenesis
Our aim is to understand the mechanisms behind hantavirus pathogenesis and the acute and long-term consequences of hantavirus-infection. Hantaviruses can cause two severe acute zoonotic diseases; hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardio-pulmonary syndrome (HCPS) in the Americas with high case-fatality rates.
About our research
Our aim is to understand the mechanisms behind hantavirus pathogenesis and the acute and long-term consequences of hantavirus-infection. We focus on the capacity of hantaviruses to affect normal cell signaling and functions, especially cell death, immune and inflammatory responses. The ultimate goal is to generate a better understanding of the details of hantavirus-induced pathogenesis to aid in the development of specific treatment of patients.
Vaccines and specific therapy is lacking. Further, infected patients show increased risks for heart attack and stroke during, and an increased risk for lymphoma after, the acute phase of infection. Altogether, this shows that hantaviruses affect human health in several different ways. In contrast to humans, natural hosts are asymptomatically infected - why hantaviruses cause disease in humans is unknown.
Group leader
Jonas Klingström
Associate Professor, PhD, Group leaderGroup members
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Projects
Hantavirus-mediated inhibition of cell death; mechanisms and consequences
Hantaviruses have very strong anti-apoptotic effects. We are investigating in detail the mechanisms behind how hantaviruses protect infected cells from being killed by cytotoxic lymphocytes and via other apoptosis-inducing pathways. We further investigate the possible consequences of hantavirus-mediated inhibition of apoptosis on the function of infected cells.
Hantavirus-mediated deregulation of inflammatory responses
Understanding the mechanisms behind how hantaviruses cause hyperinflammation in HFRS/HPS-patients has the potential to reveal important insights into pathogenesis behind human hantavirus-infection. We investigate the effects hantaviruses have on Natural Killer cell, Dendritic cell and endothelial/epithelial cell functions and responses. This might also prove valuable for our understanding of other severe zoonotic emerging viral diseases, like other hemorrhagic fevers caused by e.g. Ebola and Dengue virus.
Acute and long-term consequences of human hantavirus-infection
We analyze immune responses and functions in Swedish HFRS-patients to characterize the impact hantavirus-infection has on our immune system. We also analyze the acute and long-term consequences of hantavirus-infection in Swedish HFRS-patients as compared to the Swedish total population to characterize the effects of human hantavirus-infection on the public health.
Research Support
- The Swedish Research Council (VR)
- CIMED
- KAW/SciLifeLab
Selected publications
2021
Expansion of SARS-CoV-2-Specific Antibody-Secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients.
Varnaitė R, García M, Glans H, Maleki KT, Sandberg JT, Tynell J, Christ W, Lagerqvist N, Asgeirsson H, Ljunggren HG, Ahlén G, Frelin L, Sällberg M, Blom K, Klingström J, Gredmark-Russ S
J Immunol 2020 11;205(9):2437-2446
Innate lymphoid cell composition associates with COVID-19 disease severity.
García M, Kokkinou E, Carrasco García A, Parrot T, Palma Medina LM, Maleki KT, Christ W, Varnaitė R, Filipovic I, Ljunggren HG, Björkström NK, Folkesson E, Rooyackers O, Eriksson LI, Sönnerborg A, Aleman S, Strålin K, Gredmark-Russ S, Klingström J, Mjösberg J,
Clin Transl Immunology 2020 ;9(12):e1224
2020
Hantavirus inhibits apoptosis by preventing mitochondrial membrane potential loss through up-regulation of the pro-survival factor BCL-2.
Solà-Riera C, García M, Ljunggren HG, Klingström J
PLoS Pathog. 2020 Feb;16(2):e1008297
Puumala and Andes Orthohantaviruses Cause Transient Protein Kinase R-Dependent Formation of Stress Granules.
Christ W, Tynell J, Klingström J
J. Virol. 2020 Jan;94(3):
2019
Hantavirus Inhibits TRAIL-Mediated Killing of Infected Cells by Downregulating Death Receptor 5.
Solà-Riera, Gupta S, Maleki KT, González-Rodriguez P, Saidi D3, Zimmer C, Vangeti S, Rivino L, Leo Y, Lye D, MacAry P, Ahlm C, Smed-Sörensen A, Joseph B, Björkström N, Ljunggren HG, Klingström J.
Cell Rep 2019 Aug;28(8):2124-2139.e6
Serum Markers Associated with Severity and Outcome of Hantavirus Pulmonary Syndrome.
Maleki KT, García M, Iglesias A, Alonso D, Ciancaglini M, Hammar U, Ljunggren HG, Schierloh P, Martínez VP, Klingström J.
J. Infect. Dis. 2019 May;219(11):1832-1840
Orthohantaviruses belonging to three phylogroups all inhibit apoptosis in infected target cells.
Solà-Riera C, Gupta S, Ljunggren HG, Klingström J.
Sci Rep 2019 Jan;9(1):834
Innate and adaptive immune responses against human Puumala virus infection: immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus-associated syndromes.
Maleki KT, García M, Iglesias A, Alonso D, Ciancaglini M, Hammar U, Ljunggren HG, Schierloh P, Martínez VP, Klingström J.
J. Intern. Med. 2019 May;285(5):510-523
2013-2018
Risk of Venous Thromboembolism Following Hemorrhagic Fever With Renal Syndrome: A Self-controlled Case Series Study.
Connolly-Andersen AM, Whitaker H, Klingström J, Ahlm C
Clin. Infect. Dis. 2018 01;66(2):268-273
Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways.
Scholz S, Baharom F, Rankin G, Maleki KT, Gupta S, Vangeti S, Pourazar J, Discacciati A, Höijer J, Bottai M, Björkström N, Rasmuson J, Evander M, Blomberg A, Ljunggren HG, Klingström J, Ahlm C, Smed-Sörensen A.
PLoS Pathog. 2017 Jun;13(6):e1006462
NK cell activation in human hantavirus infection explained by virus-induced IL-15/IL15Rα expression.
Braun M, Björkström N, Gupta S, Sundström K, Ahlm C, Klingström J, Ljunggren HG.
PLoS Pathog. 2014 Nov;10(11):e1004521
Increased risk for lymphoma following hemorrhagic fever with renal syndrome.
Klingström J, Granath F, Ekbom A, Björkström NK, Ljunggren HG
Clin. Infect. Dis. 2014 Oct;59(8):1130-2
Increased risk of acute myocardial infarction and stroke during hemorrhagic fever with renal syndrome: a self-controlled case series study.
Connolly-Andersen AM, Hammargren E, Whitaker H, Eliasson M, Holmgren L, Klingström J, Ahlm C.
Circulation 2014 Mar;129(12):1295-302
Hantavirus-infection confers resistance to cytotoxic lymphocyte-mediated apoptosis.
Gupta S, Braun M, Tischler ND, Stoltz M, Sundström KB, Björkström NK, Ljunggren HG, Klingström J.
PLoS Pathog. 2013 Mar;9(3):e1003272
Puumala virus infections associated with cardiovascular causes of death.
Connolly-Andersen AM, Ahlm K, Ahlm C, Klingström J
Emerging Infect. Dis. 2013 Jan;19(1):126-8