African swine fever (ASF) has become so widespread in Europe and other parts of the world in recent years that it can be described as a panzootic disease. There are currently no internationally approved vaccines or treatments for the disease, which is fatal to domestic and wild pigs. A team led by the Friedrich-Loeffler-Institut (FLI) and the Roslin Institute of the University of Edinburgh set out to find out which pig genes are needed for the African swine fever virus (ASFV) to replicate. Their study shows that a gene from the pig's immune system is crucial. This provides important new insights into the biology of the ASF virus, which can serve as a basis for future research approaches. In particular, the identified gene offers a suitable approach for the development of effective therapeutics against ASFV infections or ASFV-resistant pig breeds.
ASFV has a large DNA genome from which more than 160 viral proteins are produced in infected cells. Little is known about the functions of many of these viral proteins. It is also not clear which cellular proteins ASFV uses to enter the host cell.
To identify host proteins important for ASFV, scientists at The Roslin Institute provided a CRISPR/Cas9 expression library as a molecular tool that allowed their colleagues at The FLI to knock out all known genes in the pig genome individually in vitro and test the resulting cell cultures for susceptibility to ASFV infection. This led to the identification of several genes of the major histocompatibility complex II (MHC II) as relevant factors for the reproductive capacity of ASFV. In particular, the MHC II receptor protein SLA-DM was shown to be required for efficient ASFV infection. Therefore, SLA-DM may be a suitable target protein for the development of effective therapeutics against ASF or ASFV resistant pig breeds.
The study has been published in Scientific Reports.
Pannhorst, K., Carlson, J., Hölper, J.E. et al. The non-classical major histocompatibility complex II protein SLA-DM is crucial for African swine fever virus replication. Sci Rep 13, 10342 (2023).