PRRSV-OUT – PRRSV-OUT

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pig pathogen significantly impacting animal
health, productivity and welfare. Prophylactic and treatment options are currently limited, partially due to the lack of appropriate cell culture
systems limiting the study of virus-host interactions in vitro. To advance the breeding of disease resistant animals and optimise vaccination
strategies, and development of specific inhibitors, an in-depth knowledge of host cell factors essential for PRRSV
infection is fundamental. By combining transnational interdisciplinary expertise in virology, genome editing and bioinformatics, this project
aims to enhance our understanding of the host genes critical for PRRSV infection to develop new strategies to combat PRRSV. We will exploit
genomic tools and a novel porcine alveolar macrophage cell line (iMAC) to provide the research community with host cell factors essential
for the PRRSV replication cycle and novel tools for genomic screens and genetic modification of pigs. The specific objectives of our project
are (1) optimisation and comparison of porcine libraries for genome wide knock-out (KO) screens; (2) identification of essential host factors
in iMAC, vervet monkey derived MARC-145 cells and primary porcine alveolar macrophages by KO screens; (3) functional association of
identified factors with the interactome of already known PRRSV host factors and genetic traits associated with increased resistance to PRRSV infection; (4) functional characterization of novel host factors; (5) generation of optimised vectors for genome modification in porcine
(primary) cells.
The novel iMAC cell line, genome-wide sgRNA libraries, and improved vectors will be valuable resources for broader research, including
studies on other porcine pathogens and xenograft research. This could significantly advance our capabilities in pig health research and
PRRSV management.