Harnessing genomics to fight prrsv discovery of essential host factors and their functional association with resistance

Project summary

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.