Influence of African Swine Fever Virus on Host Gene Transcription within Peripheral Blood Mononuclear Cells from Infected Pigs

Abstract

African swine fever virus (ASFV) has become a global threat to the pig production industry and has caused enormous economic losses in many countries in recent years. Peripheral blood mononuclear cells (PBMCs) from pigs infected with ASFV not only express ASFV genes (almost 200 in number) but have altered patterns of host gene expression as well. Both up- and down-regulation of host cell gene expression can be followed using RNAseq on poly(A)+ mRNAs harvested from the PBMCs of pigs collected at different times post-infection. Consistent with the time course of changes in viral gene expression, only few and limited changes in host gene expression were detected at 3 days post-infection (dpi), but by 6 dpi, marked changes in the expression of over 1300 host genes were apparent. This was co-incident with the major increase in viral gene expression. The majority of the changes in host gene expression were up-regulation, but many down-regulated genes were also identified. The patterns of changes in gene expression within the PBMCs detected by RNAseq were similar in each of the four infected pigs. Furthermore, changes in the expression of about twenty selected host genes, known to be important in host defence and inflammatory responses, were confirmed using high-throughput microfluidic qPCR assays.

Increased Presence of Circulating Cell-Free, Fragmented, Host DNA in Pigs Infected with Virulent African Swine Fever Virus

“…Generally, the animals die within a week of being infected. We have described previously the changes in the expression of over 1000 genes in the PBMCs isolated from ASFV-infected pigs [ 34 ]. It is well-established that major changes occur within the spleen and lymph nodes of ASFV-infected animals [ 11 , 17 ] and significant losses of B- and T- lymphocytes can occur without these cells being infected themselves, presumably in response to signals received from the infected monocytes [ 16 , 20 ].…”

Release of fragmented host, cell-free, genomic DNA into the circulation of pigs during infection by virulent African swine fever virus

“…Generally, the animals die within a week of being infected. We have described previously changes in the expression of over 1000 genes in the PBMCs isolated from ASFV-infected pigs [31]. It is well established that major changes occur within the spleen and lymph nodes of ASFV-infected animals [11, 17] and significant loss of B- and T- lymphocytes can occur without these cells being infected themselves, presumably in response to signals received from the infected monocytes [16, 20].…”