Ochratoxin A-induced autophagy in vitro and in vivo promotes porcine circovirus type 2 replication.
Identifieur interne : 000D04 ( Main/Exploration ); précédent : 000D03; suivant : 000D05Ochratoxin A-induced autophagy in vitro and in vivo promotes porcine circovirus type 2 replication.
Auteurs : Gang Qian [République populaire de Chine] ; Dandan Liu [République populaire de Chine] ; Junfa Hu [République populaire de Chine] ; Fang Gan [République populaire de Chine] ; Lili Hou [République populaire de Chine] ; Xingxiang Chen [République populaire de Chine] ; Kehe Huang [République populaire de Chine]Source :
- Cell death & disease [ 2041-4889 ] ; 2017.
Descripteurs français
- KwdFr :
- ADN viral (), Animaux, Autophagie (), Autophagie (génétique), Bécline-1 (génétique), Circovirus (), Circovirus (génétique), Circovirus (pathogénicité), Infections à Circoviridae (génétique), Infections à Circoviridae (médecine vétérinaire), Infections à Circoviridae (virologie), Ochratoxines (administration et posologie), Protéine-5 associée à l'autophagie (génétique), Protéines associées aux microtubules, Régulation de l'expression des gènes viraux (génétique), Répartition dans les tissus, Réplication virale (), Suidae.
- MESH :
- administration et posologie : Ochratoxines.
- génétique : Autophagie, Bécline-1, Circovirus, Infections à Circoviridae, Protéine-5 associée à l'autophagie, Régulation de l'expression des gènes viraux.
- médecine vétérinaire : Infections à Circoviridae.
- pathogénicité : Circovirus.
- virologie : Infections à Circoviridae.
- ADN viral, Animaux, Autophagie, Circovirus, Protéines associées aux microtubules, Répartition dans les tissus, Réplication virale, Suidae.
English descriptors
- KwdEn :
- Animals, Autophagy (drug effects), Autophagy (genetics), Autophagy-Related Protein 5 (genetics), Beclin-1 (genetics), Circoviridae Infections (genetics), Circoviridae Infections (veterinary), Circoviridae Infections (virology), Circovirus (drug effects), Circovirus (genetics), Circovirus (pathogenicity), DNA, Viral (drug effects), Gene Expression Regulation, Viral (genetics), Microtubule-Associated Proteins, Ochratoxins (administration & dosage), Swine, Tissue Distribution, Virus Replication (drug effects).
- MESH :
- chemical , administration & dosage : Ochratoxins.
- chemical , drug effects : DNA, Viral.
- chemical , genetics : Autophagy-Related Protein 5, Beclin-1.
- drug effects : Autophagy, Circovirus, Virus Replication.
- genetics : Autophagy, Circoviridae Infections, Circovirus, Gene Expression Regulation, Viral.
- pathogenicity : Circovirus.
- veterinary : Circoviridae Infections.
- virology : Circoviridae Infections.
- Animals, Microtubule-Associated Proteins, Swine, Tissue Distribution.
Abstract
Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium. Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. Recently, we reported that low doses of OTA promoted PCV2 replication in vitro and in vivo, but the underlying mechanism needed further investigation. The present studies further confirmed OTA-induced PCV2 replication promotion as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells. Our studies also showed that OTA induced autophagy in PK-15 cells, as assessed by the markedly increased expression of microtubule-associated protein 1 light chain 3 (LC3)-II, autophagy-related protein 5 (ATG5), and Beclin-1 and the accumulation of green fluorescent protein (GFP)-LC3 dots. OTA induced complete autophagic flux, which was detected by monitoring p62 degradation and LC3-II turnover using immunoblotting. Inhibition of autophagy by 3-methylademine (3-MA) and chloroquine (CQ) significantly attenuated OTA-induced PCV2 replication promotion. The observed phenomenon was further confirmed by the knock-down of ATG5 or Beclin-1 by specific siRNA. Further studies showed that N-acetyl-L-cysteine (NAC), an ROS scavenger could block autophagy induced by OTA, indicating that ROS may be involved in the regulation of OTA-induced autophagy. Furthermore, we observed significant increases in OTA concentrations in lung, spleen, kidney, liver and inguinal lymph nodes (ILN) and bronchial lymph nodes (BLN) of pigs fed 75 and 150 μg/kg OTA compared with controls in vivo. Administration of 75 μg/kg OTA significantly increased PCV2 replication and autophagy in the lung, spleen, kidney and BLN of pigs. Taken together, it could be concluded that OTA-induced autophagy in vitro and in vivo promotes PCV2 replication.
DOI: 10.1038/cddis.2017.303
PubMed: 28661479
Affiliations:
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Le document en format XML
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Nanjing 210095, Jiangsu Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province</wicri:regionArea><wicri:noRegion>Jiangsu Province</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Junfa" sort="Hu, Junfa" uniqKey="Hu J" first="Junfa" last="Hu">Junfa Hu</name><affiliation wicri:level="1"><nlm:affiliation>College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province</wicri:regionArea><wicri:noRegion>Jiangsu Province</wicri:noRegion></affiliation></author><author><name sortKey="Gan, Fang" sort="Gan, Fang" uniqKey="Gan F" first="Fang" last="Gan">Fang Gan</name><affiliation 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Xingxiang" sort="Chen, Xingxiang" uniqKey="Chen X" first="Xingxiang" last="Chen">Xingxiang Chen</name><affiliation wicri:level="1"><nlm:affiliation>College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province</wicri:regionArea><wicri:noRegion>Jiangsu Province</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Kehe" sort="Huang, Kehe" uniqKey="Huang K" first="Kehe" last="Huang">Kehe Huang</name><affiliation wicri:level="1"><nlm:affiliation>College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu 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de l'expression des gènes viraux</term></keywords><keywords scheme="MESH" qualifier="médecine vétérinaire" xml:lang="fr"><term>Infections à Circoviridae</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Circovirus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Circovirus</term></keywords><keywords scheme="MESH" qualifier="veterinary" xml:lang="en"><term>Circoviridae Infections</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à Circoviridae</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Circoviridae Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Microtubule-Associated Proteins</term><term>Swine</term><term>Tissue Distribution</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ADN viral</term><term>Animaux</term><term>Autophagie</term><term>Circovirus</term><term>Protéines associées aux microtubules</term><term>Répartition dans les tissus</term><term>Réplication virale</term><term>Suidae</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium. Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. Recently, we reported that low doses of OTA promoted PCV2 replication in vitro and in vivo, but the underlying mechanism needed further investigation. The present studies further confirmed OTA-induced PCV2 replication promotion as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells. Our studies also showed that OTA induced autophagy in PK-15 cells, as assessed by the markedly increased expression of microtubule-associated protein 1 light chain 3 (LC3)-II, autophagy-related protein 5 (ATG5), and Beclin-1 and the accumulation of green fluorescent protein (GFP)-LC3 dots. OTA induced complete autophagic flux, which was detected by monitoring p62 degradation and LC3-II turnover using immunoblotting. Inhibition of autophagy by 3-methylademine (3-MA) and chloroquine (CQ) significantly attenuated OTA-induced PCV2 replication promotion. The observed phenomenon was further confirmed by the knock-down of ATG5 or Beclin-1 by specific siRNA. Further studies showed that N-acetyl-L-cysteine (NAC), an ROS scavenger could block autophagy induced by OTA, indicating that ROS may be involved in the regulation of OTA-induced autophagy. Furthermore, we observed significant increases in OTA concentrations in lung, spleen, kidney, liver and inguinal lymph nodes (ILN) and bronchial lymph nodes (BLN) of pigs fed 75 and 150 μg/kg OTA compared with controls in vivo. Administration of 75 μg/kg OTA significantly increased PCV2 replication and autophagy in the lung, spleen, kidney and BLN of pigs. Taken together, it could be concluded that OTA-induced autophagy in vitro and in vivo promotes PCV2 replication.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Qian, Gang" sort="Qian, Gang" uniqKey="Qian G" first="Gang" last="Qian">Gang Qian</name></noRegion><name sortKey="Chen, Xingxiang" sort="Chen, Xingxiang" uniqKey="Chen X" first="Xingxiang" last="Chen">Xingxiang Chen</name><name sortKey="Gan, Fang" sort="Gan, Fang" uniqKey="Gan F" first="Fang" last="Gan">Fang Gan</name><name sortKey="Hou, Lili" sort="Hou, Lili" uniqKey="Hou L" first="Lili" last="Hou">Lili Hou</name><name sortKey="Hu, Junfa" sort="Hu, Junfa" uniqKey="Hu J" first="Junfa" last="Hu">Junfa Hu</name><name sortKey="Huang, Kehe" sort="Huang, Kehe" uniqKey="Huang K" first="Kehe" last="Huang">Kehe Huang</name><name sortKey="Liu, Dandan" sort="Liu, Dandan" uniqKey="Liu D" first="Dandan" last="Liu">Dandan Liu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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