Evaluation of Lesions and Viral Antigen Distribution in Domestic Pigs Inoculated Intranasally with African Swine Fever Virus Ken05/Tk1 (Genotype X).

Pedro J Sánchez-Cordón,Emil Wikström-Lassa,Linda K Dixon,Daniel Hicks,Alejandro Núñez,Ronan R Mccarthy,Aleksija Neimanis,Helen R Crooke,Tobias Floyd,Rebecca Strong,Stephen Mccleary,Dolores Gavier-Widén

doi:10.3390/pathogens10060768

Abstract

The understanding of the pathogenic mechanisms and the clinicopathological forms caused by currently circulating African swine fever virus (ASFV) isolates is incomplete. So far, most of the studies have been focused on isolates classified within genotypes I and II, the only genotypes that have circulated outside of Africa. However, less is known about the clinical presentations and lesions induced by isolates belonging to the other twenty-two genotypes. Therefore, the early clinicopathological identification of disease outbreaks caused by isolates belonging to, as yet, not well-characterised ASFV genotypes may be compromised, which might cause a delay in the implementation of control measures to halt the virus spread. To improve the pathological characterisation of disease caused by diverse isolates, we have refined the macroscopic and histopathological evaluation protocols to standardise the scoring of lesions. Domestic pigs were inoculated intranasally with different doses (high, medium and low) of ASFV isolate Ken05/Tk1 (genotype X). To complement previous studies, the distribution and severity of macroscopic and histopathological lesions, along with the amount and distribution of viral antigen in tissues, were characterised by applying the new scoring protocols. The intranasal inoculation of domestic pigs with high doses of the Ken05/Tk1 isolate induced acute forms of ASF in most of the animals. Inoculation with medium doses mainly induced acute forms of disease. A less severe but longer clinical course, typical of subacute forms, characterised by the presence of more widespread and severe haemorrhages and oedema, was observed in one pig inoculated with the medium dose. The severity of vascular lesions (haemorrhages and oedema) induced by high and medium doses was not associated with the amount of virus antigen detected in tissues, therefore these might be attributed to indirect mechanisms not evaluated in the present study. The absence of clinical signs, lesions and detectable levels of virus genome or antigen in blood from the animals inoculated with the lowest dose ruled out the existence of possible asymptomatic carriers or persistently infected pigs, at least for the 21 days period of the study. The results corroborate the moderate virulence of the Ken05/Tk1 isolate, as well as its capacity to induce both the acute and, occasionally, subacute forms of ASF when high and medium doses were administered intranasally.

Highlights

African swine fever (ASF) is a devastating viral haemorrhagic disease caused by a complex DNA arbovirus, the ASF virus (ASFV), the only member of the Asfarviridae family [1] that affects all members of the family Suidae [2]
The rest of the animals developed an acute form of ASF, displaying short incubation periods, short clinical courses and viraemia from day 5 pi
We made use of an intranasal infection model for ASFV where the dose of infection influenced the outcome of clinical presentation, and where the correlation of clinical scores with pathological lesions was reviewed

Summary

Introduction

African swine fever (ASF) is a devastating viral haemorrhagic disease caused by a complex DNA arbovirus, the ASF virus (ASFV), the only member of the Asfarviridae family [1] that affects all members of the family Suidae [2]. ASF was first described in Kenya [3] where the virus spread from asymptomatic infected warthogs (Phacochoerus aethiopicus) to domestic pigs (Sus scrofa), causing high mortality rates in the pigs. Eurasian wild boar and feral pigs (Sus scrofa) succumb to ASFV and can transmit the virus to domestic pigs. In August 2018 the genotype II virus reached China [6], where almost half of the global pig population resides, spreading out of control to several countries in Asia and threatening the Australian continent [7]. Twenty-four distinct genotypes of ASFV have been described up to now [8,9], only a few genome sequences have been published, of which only some have sufficient data available to enable in-depth genetic investigations [1,10]. Studies to characterise the virulence and pathogenic mechanisms of isolates belonging to different genotypes have been mainly focused on viruses classified within genotype I [11,12,13,14,15,16,17,18,19,20] and genotype II [21,22,23,24,25,26], the only genotypes that have circulated outside of Africa, to date

Objectives

Methods

Results

Discussion

Conclusion