Environment, vector, or host? Using machine learning to untangle the mechanisms driving arbovirus outbreaks

Climatic, landscape, and host features are critical components in shaping out-breaks of vector-borne diseases. However, the relationship between the outbreaks of vector-borne pathogens and their environmental drivers is typically complicated, nonlinear, and mayvary by taxonomic units below the species level (e.g., strain or serotype). Here, we aim tountangle how these complex forces shape the risk of outbreaks of Bluetongue virus (BTV); avector-borne pathogen that is continuously emerging and re-emerging across Europe, with sev-ere economic implications. We tested if the ecological predictors of BTV outbreak risk wereserotype-specific by examining the most prevalent serotypes recorded in Europe (1, 4, and 8).We used a robust machine learning (ML) pipeline and 23 relevant environmental features to fitpredictive models to 24,245 outbreaks reported in 25 European countries between 2000 and2019. Our ML models demonstrated high predictive performance for all BTV serotypes (accu-racies>0.87) and revealed strong nonlinear relationships between BTV outbreak risk andenvironmental and host features. Serotype-specific analysis suggests, however, that each of themajor serotypes (1, 4, and 8) had a unique outbreak risk profile. For example, temperature andmidge abundance were as the most important characteristics shaping serotype 1, whereas forserotype 4 goat density and temperature were more important. We were also able to identifystrong interactive effects between environmental and host characteristics that were also sero-type specific. Our ML pipeline was able to reveal more in-depth insights into the complex epi-demiology of BTVs and can guide policymakers in intervention strategies to help reduce theeconomic implications and social cost of this important pathogen

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

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.This work was funded by InnovateUK Crop and Livestock Disease Challenges: Validation of Genome Edited Disease Resistant Pig grant BB/M028313/1 and by Genus PLC. Work at the APHA was completed under an InnovateUK and Genus funded sub-contract, CSKN0019. In addition the work was in part supported by BBSRC ISPG funding BBS/E/D/10002071, BBS/E/D/20002172, BBS/E/D/20002174, BB/P013740/1 and BB/P013759/1 to the Roslin Institute