One Health and Cattle Genetic Resources: Mining More than 500 Cattle Genomes to Identify Variants in Candidate Genes Potentially Affecting Coronavirus Infections

SIMPLE SUMMARY: The conservation and exploitation of cattle genetic resources for selection and breeding purposes are important for the definition of sustainable livestock production sectors. One Health approaches should be integrated into these activities to reduce the risk posed by many zoonoses. Coronaviruses are emerging as important zoonotic agents, with the potential to easily cross species barriers, as also recently demonstrated by the COVID-19 pandemic derived by SARS-CoV-2. Genetic resistance to coronavirus infections can be determined by variants of the host (animal) genome segregating within species. In this study, we mined the genome of more than 500 cattle to identify variants that could be involved so as to define different levels of susceptibility and/or resistance to coronavirus diseases in this important livestock species. Using comparative analyses across species, we identified several single amino acid polymorphisms that might alter the function of key proteins involved in the basic biological mechanisms underlying the infection processes in cattle. This study provided new elements to consider genetic variability of the host (cattle) as a potential risk factor to be considered in One Health perspectives. ABSTRACT: Epidemiological and biological characteristics of coronaviruses and their ability to cross species barriers are a matter of increasing concerns for these zoonotic agents. To prevent their spread, One Health approaches should be designed to include the host (animal) genome variability as a potential risk factor that might confer genetic resistance or susceptibility to coronavirus infections. At present, there is no example that considers cattle genetic resources for this purpose. In this study, we investigated the variability of six genes (ACE2, ANPEP, CEACAM1 and DPP4 encoding for host receptors of coronaviruses; FURIN and TMPRSS2 encoding for host proteases involved in coronavirus infection) by mining whole genome sequencing datasets from more than 500 cattle of 34 Bos taurus breeds and three related species. We identified a total of 180 protein variants (44 already known from the ARS-UCD1.2 reference genome). Some of them determine altered protein functions or the virus–host interaction and the related virus entry processes. The results obtained in this study constitute a first step towards the definition of a One Health strategy that includes cattle genetic resources as reservoirs of host gene variability useful to design conservation and selection programs to increase resistance to coronavirus diseases.