Species-specific evaluation of Nipah virus pathogenesis using xenochimeric mice

• Applicant: Dr. Beatriz Escudero Pérez
• Subject Area: Virology ; Immunology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 549978628

Nipah virus (NiV) is a zoonotic emergent virus that can cause an acute respiratory illness and fatal encephalitis in humans. NiV fatality rate can be up to 92% in humans. NiV can also cause severe disease in domestic animals such as swine, resulting in significant economic losses for farmers. Despite the fact that NiV represents a threat for global public health and causes yearly NiV outbreaks affecting humans and swine, no approved vaccines or treatments are yet available. While sometimes lacking clinical disease, NiV infection rate in swine is estimated to 100% with a low mortality rate (<5%) in adults but high (aprox. 40%) in suckling pigs. In contrast to symptomatically infected swine that frequently develop respiratory diseases, only up to 27 % of NiV-infected human patients exhibit respiratory symptoms. These differences between humans and swine disease severity and the mechanisms that determine NiV pathogenicity have not yet been fully understood. The overarching goal of this project is to compare human and swine NiV infection in vitro and in vivo to dissect the mechanisms responsible for species-specific Nipah virus pathogenesis. In order to do so, we are going to (i) determine the differences in the ability of NiV to target human and swine immune and respiratory cells and (ii) generate xenochimeric mice containing either human or swine immune system to compare the species-specific immune responses during NiV infection. Determining the specific factors that render some species susceptible to Nipah virus has not yet been elucidated and it is crucial to decrease the threat that NiV represents for global public health. Other putative outcomes of this project are as follows: 1. It could provide a system to study species-specific pathogenesis. By using the mouse as the same in vivo platform but containing the immune system of the species of choice, will allow to compare the host immune responses in vivo. This will impact pathogenesis and ecology studies. 2. It could provide an in vivo model for testing therapeutics against NiV and other viruses. 3. This animal model can bridge the research interests of more than one field such as immunology, virology, ecology and therapeutics amongst others, thus providing essential interrelated information to all of them. Moreover, fulfilling these objectives will provide a platform to investigate the putative pathogenicity of newly emerging viruses in humans, and could also facilitate host reservoir immunity studies applicable to other viruses of interest.

• DFG Programme: Research Grants