Detailseite
Projekt
Phylogenetische und experimentelle Rekonstruktion zoonotischer Transmission von humanen Coronaviren
Antragsteller
Professor Dr. Christian Drosten
Fachliche Zuordnung
Virologie
Förderung
Förderung von 2013 bis 2017
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 226350623
The SARS crisis revealed many mechanistic details associated with adaptation of emerging viruses to the human population following zoonotic transmission. However, there is a lack of knowledge concerning early events prior to the pandemic, and it remains elusive which epidemiological, ecological, viral or host-specific factors may have been critical for crossing the species barrier. The relatively large phylogenetic distance between SARS-like coronaviruses (CoVs) identified in bats and human SARS-CoV isolates led to the ideas that there is either a yet undetected intermediate host that facilitated SARS(-like)-CoV transmission to humans, or alternatively, there is a yet undetected close relative of SARS-CoV circulating in bats or other mammalian species.In contrast, the close phylogenetic relationship between HCoV-229E and the recently identified bat 229E-like CoV, strongly suggests that the MRCA of this virus pair has evolved in bats and that HCoV-229E has adapted to the human population following a direct transmission from bats to humans about 200-300 years ago. This proposal aims to remodel these early transmission events by reconstruction of the most recent common ancestor (MRCA) and evolutionary intermediates and experimental assessment of critical species barriers. We aim to combine the available sequence information with our experimental repertoire that comprises bioinformatic and phylogenetic analyses, as well as reverse genetics for HCoV-229E. The overall goal is to determine at which stage during virus evolution zoonotic transmission could occur. We will primarily evaluate the most likely determinants of CoV cross species transmission, namely CoV spike – receptor interaction and CoV-induced innate immune responses. The anticipate results will not only allow us to assess the likelihood and risk of future CoV zoonotic transmission, but also to develop efficacious strategies to prevent and control CoV infections.
DFG-Verfahren
Schwerpunktprogramme
Internationaler Bezug
Schweiz
Partnerorganisation
Schweizerischer Nationalfonds (SNF)
Mitverantwortlich
Professor Dr. Volker Thiel
