Stiftung Tierärztliche Hochschule Hannover (TiHo)

Inhibition of caspase-1 prolongs survival of mice infected with rabies virus

Affiliation
Erasmus Medical Centre Rotterdam, The Netherlands,. Electronic address: koraka@viroclinics.com.
Koraka, Penelope;
ORCID
0000-0002-7462-7303
Affiliation
Erasmus Medical Centre Rotterdam, The Netherlands,; Artemis One Health Research Foundation, Delft, The Netherlands.
Martina, Byron;
Affiliation
Department of Virology, National Veterinary Research Institute, Partyzantów 57 Avenue, 24-100 Puławy, Poland.
Smreczak, Marcin;
GND
1025310977
Affiliation
Department of Virology, National Veterinary Research Institute, Partyzantów 57 Avenue, 24-100 Puławy, Poland.
Orłowska, Anna;
ORCID
0000-0002-0589-0714
Affiliation
Department of Virology, National Veterinary Research Institute, Partyzantów 57 Avenue, 24-100 Puławy, Poland.
Marzec, Anna;
Affiliation
Department of Virology, National Veterinary Research Institute, Partyzantów 57 Avenue, 24-100 Puławy, Poland.
Trebas, Pawel;
Affiliation
Artemis One Health Research Foundation, Delft, The Netherlands.
Roose, Jouke M;
ORCID
0000-0001-8856-9135
Affiliation
Erasmus Medical Centre Rotterdam, The Netherlands.
Begeman, Lineke;
GND
1213271622
ORCID
0000-0002-7973-7405
Affiliation
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
Gerhauser, Ingo;
ORCID
0000-0001-9184-4134
Affiliation
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
Wohlsein, Peter;
GND
142929565
ORCID
0000-0001-8151-5644
Affiliation
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany; Center for Systems Neuroscience (ZSN), Hannover, Germany.
Baumgärtner, Wolfgang;
Affiliation
Department of Virology, National Veterinary Research Institute, Partyzantów 57 Avenue, 24-100 Puławy, Poland.
Zmudzinski, Jan;
GND
130395951
ORCID
0000-0001-6535-3497
Affiliation
Artemis One Health Research Foundation, Delft, The Netherlands; Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine, Hannover, Germany.
Osterhaus, Albert

Rabies virus infects almost all mammals resulting in lethal disease. To date there is no treatment available for symptomatic rabies and there is an urgent need to develop treatment strategies that would prolong survival, thereby providing a window of opportunity for the host to mount a protective immune response. We hypothesized that both virus and excessive immune response contribute to disease and that interfering with both is necessary to prevent lethal disease. Here, we have inhibited the pro-inflammatory response associated with pyroptosis and showed that inhibition of CASP-1 had a beneficial effect on survival time. Our results confirm that some inflammatory responses may be involved in the pathogenesis of severe disease and the results suggest that effective intervention includes inhibition of virus and host response.

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