Autophagy inhibitors reduce avian-reovirus-mediated apoptosis in cultured cells and in chicken embryos.
Avian reovirus (ARV)-induced apoptosis contributes to the pathogenesis of reovirus in infected chickens. However, methods for effectively reducing ARV-triggered apoptosis remain to be explored. Here, we show that pretreatment with chloroquine (CQ) or E64d plus pepstatin A decreases ARV-mediated apoptosis in chicken DF-1 cells. By acting as autophagy inhibitors, CQ and E64d plus pepstatin A increase microtubule-associated protein 1 light chain 3-II (LC3II) accumulation in ARV-infected cells, which results in decreased ARV protein synthesis and virus yield and thereby contributes to the reduction of apoptosis. Furthermore, ARV-mediated apoptosis in the bursa, heart and intestines of chicken embryos is attenuated by CQ and E64d plus pepstatin A treatment. Importantly, treatment with these autophagy inhibitors increases the survival of infected chicken embryos. Together, our data suggest that pharmacological inhibition of autophagy might represent a novel strategy for reducing ARV-mediated apoptosis.
Jiangsu Co-Innovation Center for Prevention and Control of Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, Jiangsu, 225009, China.
Shipeng
S
Duan
Jinghua
J
Cheng
Chenxi
C
Li
Liping
L
Yu
Xiaorong
X
Zhang
Ke
K
Jiang
Yupeng
Y
Wang
Jiansheng
J
Xu
Yantao
Y
Wu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002642:Chick Embryo; D002645:Chickens; D002738:Chloroquine / Q000008:administration & dosage*; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D030101:Orthoreovirus, Avian / Q000187:drug effects / Q000502:physiology*; D010436:Pepstatins / Q000008:administration & dosage*; D011201:Poultry Diseases / Q000188:drug therapy / Q000196:embryology / Q000503:physiopathology* / Q000821:virology; D012088:Reoviridae Infections / Q000188:drug therapy / Q000503:physiopathology / Q000662:veterinary* / Q000821:virology
D010436:Pepstatins; D002738:Chloroquine; D007930:Leucine; C108192:aloxistatin; C031375:pepstatin