A dual effect of porcine reproductive and respiratory syndrome virus replication on the phosphatidylinositol-3-kinase-dependent Akt pathway.
We have recently shown that porcine reproductive and respiratory syndrome virus (PRRSV) can undergo a productive replication in porcine monocyte-derived dendritic cells (Mo-DCs). Here, we further demonstrate that PRRSV activates the host's phosphatidylinositol-3-kinase (PI3K)-dependent Akt pathway (PI3K/Akt) to facilitate its replication in Mo-DCs at 90 min and 4 h after infection. Inhibition of PI3K/Akt by treatment with a PI3K-specific inhibitor (LY294002) prior to PRRSV infection reduced virus replication. Furthermore, inhibition of PI3K/Akt by LY294002 at 90 min and 8 h after virus infection still significantly reduced virus production, suggesting that virus replication may be dependent on the activation of PI3K/Akt. Interestingly, PRRSV inhibited PI3K/Akt at 12 h after infection. Heat-inactivated virus failed to inhibit PI3K/Akt, indicating that virus replication is essential for this inhibition. Overall, PRRSV replication exhibits a dual effect on the PI3K/Akt pathway in which both time-dependent activation and inhibition of PI3K/Akt are observed.
Zhang
Hanmo
H
Department of Biology and Microbiology, South Dakota State University, NPB 252D, Box 2140D, Brookings, SD 57007, USA.
Wang
Xiuqing
X
D000818:Animals; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003713:Dendritic Cells / Q000821:virology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology*; D015398:Signal Transduction; D013552:Swine; D019562:Viral Load; D014779:Virus Replication
D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one