Identification of factors influencing zoonotic transmission of MERS-Coronavirus in Kenya

• Applicant: Professor Dr. Marcel Müller
• Subject Area: Virology ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 405556422

Our project focuses on human pathogenic Middle East Respiratory Syndrome Coronavirus (MERS-CoV), a pre-pandemic zoonotic CoV, causing comparable clinical signs of disease in humans as SARS-CoV-2 with yet low human-to-human transmission. MERS-CoV is widespread in dromedary camels on the African continent with limited evidence of human MERS cases. On the Arabian Peninsula, however, MERS-CoV has already caused several nosocomial outbreaks since 2012 with >2,400 human infections and >900 deaths emphasizing the zoonotic potential of MERS-CoV. The factors influencing the observed differences in MERS-CoV ecology and epidemiology are still quite obscure and are addressed in this project. In the first funding period, we conducted several workshops, established a well-trained bilateral research team and set up a pipeline for diagnostic MERS-CoV testing at UoN-CEMA, Kenya. Secondly, we performed a 12-month repeated cross-sectional study with approximate daily sampling in a camel slaughterhouse in Isiolo (Northern Kenya). We showed a biphasic pattern of MERS-CoV RNA detection in camels (n=36/2,711) mainly in dry seasons. In addition, by using serologic and T cell response assays, we identified 10/48 potential subclinical MERS infections of slaughterhouse workers. Thirdly, we successfully isolated six camel-derived MERS-CoV isolates, characterized phylogenetic and genomic features, initiated reverse genetics, and determined first phenotypic features. In comparison to prototypic MERS-CoV strain EMC, Kenyan MERS-CoV clade C2 showed attenuated propagation and increased Interferon-sensitivity in advanced human cell culture models. In the next 3-year funding period, we plan to strengthen the Kenyan-German laboratory network further, support research capacities, and ensure an excellent transfer of knowledge to Kenya. Scientifically, we plan to implement and validate paralleled BSL-2 and BSL-3 laboratory-based pre-pandemic CoV risk assessment pipelines by investigating phenotypic features of newly identified MERS-CoV clade C2. Secondly, we aim to comprehend and model the biphasic MERS-CoV incidence pattern by expanding our studies on epidemiological, ecological, and virological factors facilitating MERS-CoV emergence. Thirdly, we want to gain a more comprehensive overview of the human immune response to MERS-CoV exposure and infection, to explore unrecognized human MERS cases in Kenya. Our sustainable One Health approach will provide a blueprint for future pandemics that can easily be adapted to other (respiratory) viruses and laboratories.

• DFG Programme: Research Grants
• International Connection: Kenya
• International Co-Applicant: Dr. Samuel Thumbi Mwangi