SeMet attenuates OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR signaling pathway

Abstract

Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. PCV2 replication could be promoted by low doses of ochratoxin A (OTA) as in our previous study and selenium has been shown to attenuate PCV2 replication. However, the underlying mechanism remains unclear. The aim of the study was to investigate the effects of selenomethionine (SeMet), the major component of organic selenium, on OTA-induced PCV2 replication promotion and its potential mechanism. The present study demonstrates that OTA could promote PCV2 replication as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells. In addition, OTA could activate autophagy as indicated by up-regulated light chain 3 (LC3)-II and autophagy-related protein 5 expressions and autophagosome formation. Further, OTA could down-regulate p-AKT and p-mTOR expressions and OTA-induced autophagy was inhibited when insulin was applied. SeMet at 2, 4 and 6 μM had significant inhibiting effects against OTA-induced PCV2 replication promotion. Furthermore, SeMet could attenuate OTA-induced autophagy and up-regulate OTA-induced p-AKT and p-mTOR expression inhibition. Rapamycin, an inhibitor of AKT/mTOR, could reverse the effects of SeMet on OTA-induced autophagy and the PCV2 replication promotion. In conclusion, SeMet could block OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR pathway. Therefore, SeMet supplementation could be an effective prophylactic strategy against PCV2 infections and autophagy may be a potential marker to develop novel anti-PCV2 drugs.

Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through the mTOR Signaling Pathway

“…The mTOR, LC3-I, LC3-II, S6K1, p62, fibronectin, TGF-β, and β-actin antibodies used were purchased from Abcam (anti-fibronectin antibody (ab23750), rabbit polyclonal antibody [36], anti-TGF beta 1 antibody (ab92486), rabbit polyclonal antibody [37], anti-LC3-I/II antibody (ABC929, Sigma-Aldrich), rabbit polyclonal antibody [38], anti-S6K1 antibody (ab9366), rabbit polyclonal antibody [39], anti-SQSTM1/p62 antibody (ab155686), rabbit polyclonal antibody [40] and anti-mTOR antibody (ab2732), rabbit polyclonal antibody [41]). The proteins of renal tissues were extracted by RIPA lysis buffer, which was delivered by Bio Basic Inc. (Markham, ON, Canada).…”

Selenium, Selenoproteins and Viral Infection

“…It is one of the smallest virus characterized so far, encoding only a capsid protein and two necessary proteins for viral replication [163]. It has been shown that selenomethionine supplementation in cell culture inhibits viral replication [164,165,166,167,168]. Furthermore, addition of H 2 O 2 or ochratoxin A that induced oxidative stress enhanced viral replication.…”

“…Furthermore, addition of H 2 O 2 or ochratoxin A that induced oxidative stress enhanced viral replication. This effect was prevented by selenium supplementation [164,165,166,167,168] or by selenoproteins SELENOS and GPX1 [164,165,166,167,168]. It appears that this mechanism involved the autophagy pathway [164,165,166,167,168].…”

“…This effect was prevented by selenium supplementation [164,165,166,167,168] or by selenoproteins SELENOS and GPX1 [164,165,166,167,168]. It appears that this mechanism involved the autophagy pathway [164,165,166,167,168]. Finally, in infected mice, selenium supplementation was able to decrease histological lesions by reducing inflammation [164,165,166,167,168].…”

Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through mTOR Signaling Pathway

“…The mTOR, LC3-I, LC3-II, fibronectin, TGF-β and β-actin antibody used were purchased from abcam (Anti-Fibronectin antibody (ab23750), Rabbit polyclonalantibody [72], Anti-TGF beta 1 antibody (ab92486), Rabbit polyclonal antibody [73], Anti-LC3-I/II Antibody (ABC929, Sigma-Aldrich), Rabbit polyclonal antibody [74], Anti-mTOR antibody (ab2732), Rabbit polyclonal antibody [75]). The Proteins of renal tissues were extracted by RIPA lysis buffer which was delivered by Bio BASIC INC. (Marhham Ontario L3R 8T4 Canada).…”