Jonas Klingström Project

Why do we get sick when voles dont?

Hantaviruses cause two severe zoonotic diseases: hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. There are no treatments or vaccines available, and depending on the specific hantavirus up to 40% of patients die during infection.

Puumala virus, carried by the bank vole, causes a relatively mild variant of HFRS, called nephropathia epidemica, in northern Europe including Sweden. There are several other hantaviruses that also cause disease in man, all of them have rodents as natural hosts. In rodents, infection causes a life-long but asymptomatic infection, while humans get disease but clear the infection.

It is not known why humans but not rodents get HFRS/HCPS. HFRS/HCPS are believed to be caused by the immune response raised against the virus, rather than directly by the virus infection per se. By analyzing immune responses in patients and voles we hope to identify possible differences that might explain why we get disease while rodents are protected. We are also trying to characterize how hantaviruses interfere with the normal activation, and function, of innate and adaptive immune responses, and if there are differences in how a specific hantavirus impact this in humans and natural hosts. We have found that hantaviruses are rather insensitive to the antiviral action of interferons and human saliva, and that they can avoid activating innate immune responses in infected cells. We believe that a better understanding of the mechanisms behind how hantavirus interfere with our immune system, and why this cause disease, is of importance for the development of HFRS/HCPS-specific treatments and vaccines.


Selected Publications

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, et al
PLoS Pathog. 2014 Nov;10(11):e1004521

Hantavirus-infection confers resistance to cytotoxic lymphocyte-mediated apoptosis.
Gupta S, Braun M, Tischler N, Stoltz M, Sundström K, Björkström N, et al
PLoS Pathog. 2013 Mar;9(3):e1003272

Puumala virus infections associated with cardiovascular causes of death.
Connolly-Andersen A, Ahlm K, Ahlm C, Klingström J
Emerging Infect. Dis. 2013 Jan;19(1):126-8

Rapid expansion and long-term persistence of elevated NK cell numbers in humans infected with hantavirus.
Björkström N, Lindgren T, Stoltz M, Fauriat C, Braun M, Evander M, et al
J. Exp. Med. 2011 Jan;208(1):13-21

Mortality rate patterns for hemorrhagic fever with renal syndrome caused by Puumala virus.
Hjertqvist M, Klein S, Ahlm C, Klingstrom J
Emerging Infect. Dis. 2010 Oct;16(10):1584-6

Alpha/beta interferon (IFN-alpha/beta)-independent induction of IFN-lambda1 (interleukin-29) in response to Hantaan virus infection.
Stoltz M, Klingström J
J. Virol. 2010 Sep;84(18):9140-8