Role of phosphatidylinositol 3-kinase (PI3K) and Akt1 kinase in porcine reproductive and respiratory syndrome virus (PRRSV) replication

Abstract

We have previously reported that inhibition of phosphatidylinositol 3-kinase (PI3K) reduces porcine reproductive and respiratory syndrome (PRRSV) replication. Here, we further investigate the mechanism by which PI3K inhibition affects virus replication and the role of Akt1 kinase in virus replication. We found that PI3K inhibition reduced viral gene transcription by approximately 1.5-fold. Accordingly, viral protein synthesis was significantly reduced by PI3K inhibition. Interestingly, cells overexpressing the dominant negative mutant Akt1 exhibited a significant reduction in viral gene transcription compared to cells overexpressing the constitutively active Akt1. Viral protein synthesis was also enhanced in cells overexpressing the constitutively active Akt1. Overall, our data show that both PI3K and Akt1 play a role in viral gene expression, leading to an increase in virus replication.

A genome-wide association study of fetal response to type 2 porcine reproductive and respiratory syndrome virus challenge

“…Macrophage stimulating 1 (MST1) and its receptor (MST1R) establish the MSP-RON signalling system 38 and mediate second messenger pathways within macrophages, including the Phosphatidylinositol-3-kinase (PI3K) pathway and mitogen-activated protein kinase (MAPK) pathway 39 , both of which are reported to be involved in host response to PRRSV 40 41 . The interaction between MST1 and MST1R may strongly modulate the production of interleukins (ILs), especially IL-12, IL-15 and IL-18 42 .…”

Isobavachalcone inhibits post-entry stages of the porcine reproductive and respiratory syndrome virus life cycle

“…Akt has been reported to play a positive role in PRRSV randomly selected for statistical analysis. The mean rates of positive cells among the total cells in each group were calculated using ImageJ gene expression and entry, and PRRSV replication may be dependent on the activation of PI3K/Akt [19,31,32,34]. The ERK signaling pathway has been demonstrated to play an important role in the post-entry steps of the PRRSV replication cycle and to enhance PRRSV infection [15].…”

Molecular and Cellular Mechanisms for PRRSV Pathogenesis and Host Response to Infection

“…The downstream target for PI3K is the AKT kinase that exerts the antiapoptotic effects by either phosphorylating some proapoptotic Bcl-2 family proteins or activating transcription factors to upregulate antiapoptotic genes. For PRRSV, the PI3K/Akt pathway is activated at an early stage of infection (Huo et al, 2013;Ni et al, 2015;Pujhari et al, 2014;Wang et al, 2016;Wang et al, 2014a;Zhang and Wang, 2010;Zhu et al, 2013). The Akt activation by PRRSV leads to negative regulation of the JNK pathway (Huo et al, 2013) and inhibits host cell apoptosis early in infection through inhibitory phosphorylation of pro-apoptotic protein Bad (Zhu et al, 2013).…”