Interferon gamma induces cellular protein alteration and increases replication of porcine circovirus type 2 in PK-15 cells

Abstract

Porcine circovirus type 2 (PCV2) infections may lead to the development of subclinical signs or chronic systemic syndromes, collectively known as "porcine circovirus-associated disease" (PCVAD) in swine. Interferon gamma (IFN-γ) is known to enhance PCV2 replication in vitro, and immune mediators may act as pivotal factors in triggering PCV2 infection progression toward PCVAD. We determined the effects of IFN-γ on PCV2 replication in PK-15 cells. PCV2 was cultured in the presence or absence of exogenous swine IFN-γ (swIFNγ). Growth curve analysis in PK-15 cells revealed that PCV2 could replicate to a significantly higher titer in swIFNγ medium. To investigate the host cell response upon PVC2 infection, differential expression of proteins in PCV2-infected PK-15 cells with or without swIFNγ stimulation was analyzed by proteomics (LC-MS/MS) analysis. A large proportion of the differentially expressed proteins in swIFNγ-treated PCV2-infected cells were found to be involved in apoptosis, cellular stress responses, cell survival/proliferation pathways, and inflammatory responses. We further confirmed the expression of these differentially expressed proteins at the mRNA levels by qRT-PCR. PCV2 infection in PK-15 cells in the presence of IFN-γ resulted in upregulation of cellular proteins in responses to stress, cell survival, and cell proliferation (Hsp90, MAP3K7, RAS-GTPase, c-myc, and 14-3-3 epsilon) as well as in an increase in the levels of proteins (CASP9 and TRAF5) related to the apoptosis pathways. Thus, PCV2 exploits several cellular biological processes through IFN activation for enhancing viral replication. This is the first evidence of IFN-γ promoting PCV2 replication in vitro via a mechanism similar to that used by several human viruses.

Immunogenicity and Protective Activity of Pigeon Circovirus Recombinant Capsid Protein Virus-Like Particles (PiCV rCap-VLPs) in Pigeons (Columba livia) Experimentally Infected with PiCV

“…A high level of IFN-γ is important because it is responsible for the adaptive immune cells, mainly antigen-specific T lymphocytes. Furthermore, this cytokine is also associated with innate immunity, notably with natural killer and natural killer T cells [42]. On the other hand, expression of TGF-β-2 in vaccinated and control groups was observed to have no significant statistical difference.…”

“…Furthermore, the challenge test of experimentally infected pigeons showed no detectable copies of PiCV in spleen samples post-immunization, therefore proving that the VLP treatment can significantly reduce PiCV viral loads in the spleen. Similarly, VLP immunization in mice and guinea pigs was able to significantly induce specific antibody responses to PCV2 Cap [42]. Meanwhile, in another study [43], the protective immune responses of a VLP-based PCV2 vaccine enhanced by the incorporation of a truncated form of flagellin significantly reduced viral loads in lung samples from mice.…”

PCV2 aggravated SS2 infection directly showed from differentially expressed proteome of PK15 cells

“…PCV2 is a negative modulates virus in vitro 49 . Type I and type II interferons induce cellular protein alteration and increases replication of porcine circovirus type 2 in PK15 cells 50 . PCV2 induces IFN beta expression through increased expression of genes involved in RIG-I and IRF7 signaling pathways 51 .…”

Severe Acute Respiratory Syndrome Coronavirus 2 could exploit human transcription factors involved in Interferon-mediated response

“…In the case of these speci c viruses, the IFN response process also facilitates viral replication and gene expression. For example, the genome of human immunode ciency virus (HIV), a ssRNA virus, contains motifs that are similar to the consensus binding sites for TFs belonging to the host immune genes [33,34].…”