Substitution of warthog NF-\u03baB motifs into RELA of domestic pigs is not sufficient to confer resilience to African swine fever virus

Stephen Mccleary,Simon G Lillico,C Bruce A Whitelaw,Emma L Howes,Chris Proudfoot,Helen R Crooke,Rebecca Strong,Alan J Mileham,Jane C Edwards,Alejandro Núñez,Ronan R Mccarthy,Samantha Watson,Falko Steinbach,Christine Tait-Burkard,Maeve Ballantyne,Lisa M Stevens,Pedro J Sánchez-Cordón

doi:10.1038/s41598-020-65808-1

Abstract

African swine fever virus (ASFV) causes a lethal, haemorrhagic disease in domestic swine that threatens pig production across the globe. Unlike domestic pigs, warthogs, which are wildlife hosts of the virus, do not succumb to the lethal effects of infection. There are three amino acid differences between the sequence of the warthog and domestic pig RELA protein; a subunit of the NF-κB transcription factor that plays a key role in regulating the immune response to infections. Domestic pigs with all 3 or 2 of the amino acids from the warthog RELA orthologue have been generated by gene editing. To assess if these variations confer resilience to ASF we established an intranasal challenge model with a moderately virulent ASFV. No difference in clinical, virological or pathological parameters were observed in domestic pigs with the 2 amino acid substitution. Domestic pigs with all 3 amino acids found in warthog RELA were not resilient to ASF but a delay in onset of clinical signs and less viral DNA in blood samples and nasal secretions was observed in some animals. Inclusion of these and additional warthog genetic traits into domestic pigs may be one way to assist in combating the devastating impact of ASFV.

Highlights

African swine fever virus (ASFV) causes a lethal, haemorrhagic disease in domestic swine that threatens pig production across the globe
There are three amino acid differences between the sequence of the warthog and domestic pig RELA protein; a subunit of the NF-κB transcription factor that plays a key role in regulating the immune response to infections
Domestic pigs with all 3 or 2 of the amino acids from the warthog RELA orthologue have been generated by gene editing

Summary

Introduction

African swine fever virus (ASFV) causes a lethal, haemorrhagic disease in domestic swine that threatens pig production across the globe. RELA were not resilient to ASF but a delay in onset of clinical signs and less viral DNA in blood samples and nasal secretions was observed in some animals Inclusion of these and additional warthog genetic traits into domestic pigs may be one way to assist in combating the devastating impact of ASFV. Since the Chinese pig population has declined by at least 20% and ASFV has further spread across many countries in South East Asia[3,4] Combating this global threat is hampered by the lack of a vaccine and is difficult in production systems with poor biosecurity which are more vulnerable to virus introduction and contact with wild suids[1]. In domestic pigs and wild boar acute and subacute forms dominate, Virology Department, Animal and Plant Health Agency, APHA-Weybridge, Woodham Lane, New Haw, Addlestone, KT15 3NB, UK.

Methods

Results

Conclusion