Transcriptome Profiling Reveals Features of Immune Response and Metabolism of Acutely Infected, Dead and Asymptomatic Infection of African Swine Fever Virus in Pigs

Abstract

African swine fever virus (ASFV) infection can result in lethal disease in pigs. ASFV encodes 150-167 proteins, of which only approximately 50 encoded viral structure proteins are functionally known. ASFV also encodes some nonstructural proteins that are involved in the regulation of viral transcription, viral replication and evasion from host defense. However, the understanding of the molecular correlates of the severity of these infections is still limited. The purpose of this study was to compare host and viral gene expression differences and perform functional analysis in acutely infected, dead and cohabiting asymptomatic pigs infected with ASFV by using RNA-Seq technique; healthy pigs were used as controls. A total of 3,760 and 2,874 upregulated genes and 4,176 and 2,899 downregulated genes were found in healthy pigs vs. acutely infected, dead pigs or asymptomatic pigs, respectively. Additionally, 941 upregulated genes and 956 downregulated genes were identified in asymptomatic vs. acutely infected, dead pigs. Different alternative splicing (AS) events were also analyzed, as were gene chromosome locations, and protein-protein interaction (PPI) network prediction analysis was performed for significantly differentially expressed genes (DEGs). In addition, 30 DEGs were validated by RT-qPCR, and the results were consistent with the RNA-Seq results. We further analyzed the interaction between ASFV and its host at the molecular level and predicted the mechanisms responsible for asymptomatic pigs based on the selected DEGs. Interestingly, we found that some viral genes in cohabiting asymptomatic pigs might integrate into host genes (DP96R, I73R and L83L) or remain in the tissues of cohabiting asymptomatic pigs. In conclusion, the data obtained in the present study provide new evidence for further elucidating ASFV-host interactions and the ASFV infection mechanism and will facilitate the implementation of integrated strategies for controlling ASF spread.

The transcriptomic insight into the differential susceptibility of African Swine Fever in inbred pigs

“…Four studies have already investigated the transcriptome profiling of the host in response to ASF. Two studies compared the pathogenesis of different strains 13 , 14 , one study investigated the effect of varied doses of the inoculated virus on host transcriptome profiling 15 , and one studied features of immune response of acutely infected, dead, and subclinical infection of ASFV in pigs 16 . To our knowledge this is the first report of the transcriptomic profile of pigs immunized with a low virulent isolate of ASFV before and after challenge with virulent virus.…”

“…The transcriptome of the various genotypes of ASF virus isolate 6 – 8 , its vector-borne tick 9 , and infected swine macrophages as the host–pathogen interaction 10 – 12 have already been studied. A few studies have surveyed the response to the infection in the host 13 – 16 . None of the latter studies have designed an infection challenge to study the transcriptome signatures of the immunization.…”

Transcriptome analysis reveals gene expression changes of pigs infected with non-lethal African swine fever virus

“…In the report of gene expression in macrophages infected with African swine fever virus CN/GS/2018 strain ( Cackett et al , 2022 ), there were 110 overlapping genes with our study. A similar study which was using transcriptome data to characterize the immune response between pigs acutely infected, dead and asymptomatic infection of ASFV in pigs, altogether 67 overlapping immune genes were shared ( Sun et al , 2021 ). Unfortunately, there were no common genes shared in these four studies, which show the complicated immune response when pigs were under ASFV attack ( Table S9 ).…”

Structure and function of African swine fever virus proteins: Current understanding

“…The ASFV genome encodes over 60 structural proteins and 100 non-structural proteins (Jia et al, 2017). Of these, approximately 50 genes encode viral structural proteins with known functions (Sun et al, 2021), although the function of many other proteins is unknown. The mechanism of ASFV infection is not completely understood, which makes vaccine development difficult.…”