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Research Group
Risk Group 4 – Comparative Immunology of Risk Group-4 Viruses

Head:
Joseph Prescott

Staff

Joseph Prescott, Ph.D.
David Wozniak, Ph.D. (Postdoctoral)

Research

Our research focuses on examining the innate and adaptive immune responses to Risk Group-4 viruses in humans, animal models of disease, and the natural animal reservoirs harboring these zoonotic pathogens. We also examine therapeutic strategies to combat these highly pathogenic viruses.

Natural reservoirs

The natural animal reservoirs of these highly pathogenic zoonotic viruses are able to circumvent disease by limiting immunopathogenic responses through various co-evolved mechanisms. A major focus is elucidating the immune responses that allow bats for harbor and transmit filoviruses without developing clinical disease. For this I work with two systems; Rousettus aegyptiacus (Egyptian fruit bats), the natural reservoir of Marburg virus, and Mops condylurus (Angolan free-tailed bats), the reservoir of Bombali virus, and a suspected reservoir of Ebola virus. We also study Lassa virus in its natural reservoir, Mastomys natalensis (Natal multimammate mouse). These studies range from in vivo infections in the BSL4 laboratory to examine the responses to infection, to ex vivo and in vitro experiments aimed at elucidating the innate responses to infection in specific cell types, such as macrophages and dendritic cells.

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Source: RKI Egyptian fruit bat liver section showing inflammatory TNF (red) responses in Kupffer cells upon experimental infection with Marburg virus (teal). RNAscope staining of RNA. Source: RKI Source: RKI

Disease models

We utilize several models that recapitulate aspects of human disease, including the Syrian hamster model for Nipah and Hendra virus disease and hantavirus cardiopulmonary syndrome (HCPS) caused by Andes virus. We also use next-gen humanized mouse models to study Ebola and Marburg virus disease and Lassa Fever. The immune responses observed in these animals are contrasted with the responses observed in the natural reservoirs that harbor these viruses to elucidate immunopathogenic responses that lead to disease. We also study the specific interactions between zoonotic viruses and their in vivo target cells, using highly pure and defined human iPS-derived cell types, such as endothelial cells and hepatocytes.

Date: 29.12.2024