Transcriptomic analysis reveals enhanced host inflammatory responses associated with TNF-α/NF-κB signaling pathway during infection with the ASFV CN/SC/2019 pA104R-K5R.

Abstract

The African swine fever virus (ASFV) is a highly contagious double-stranded DNA virus that belongs to the Asfarviridae family. Structurally, ASFV is more complex than other viruses and encodes numerous proteins within each layer. These proteins modulate viral replication in the host via a range of complex molecular mechanisms. Among them, the putative histone-like protein pA104R, which is a late viral protein, plays a crucial role in several stages of the viral life cycle. Our previous study demonstrated that lysine 5 (K5) of pA104R is essential for mediating ubiquitination-induced degradation of pA104R, and that the K5R mutant virus caused severe host inflammation in vivo. However, the underlying mechanism remains unclear. In this study, we examined the mechanism by which the pA104R mutant strain enhances ASFV replication in the host at the transcriptome level. Compared with the WT group, the mutant strain group induced more severe host inflammation by increased expression of inflammatory mediators associated with the TNF-α/NF-κB pathway and the NLRP3 inflammasome, as shown by transcriptome sequencing and Western blot. The results also suggested that ASFV CN/SC/2019 pA104R-K5R induced distinct transcriptional changes in multiple innate immune-related genes. Additionally, the ELISA results demonstrated a higher level of inflammation in cells infected with the mutant strain. This evidence suggested its potential to enhance inflammatory pathology, though further in vivo studies are needed to confirm this. This study provides new insights into the functions of key structural proteins of ASFV in viral replication and host immune modulation. It also offers important theoretical support for elucidating ASFV pathogenic mechanisms.