title: Porcine reproductive and respiratory syndrome virus induces autophagy to promote virus replication.
abstract: An increasing number of studies demonstrate that autophagy, an intrinsic mechanism that can degrade cytoplasmic components, is involved in the infection processes of a variety of pathogens. It can be hijacked by various viruses to facilitate their replication. In this study, we found that PRRSV infection significantly increases the number of double- or single-membrane vesicles in the cytoplasm of host cells in ultrastructural analysis. Our results showed the LC3-I was converted into LC3-II after virus infection, suggesting the autophagy machinery was activated. We further used pharmacological agents and shRNAs to confirm that autophagy promoted the replication of PRRSV in host cells. Confocal microscopy analysis showed that PRRSV inhibited the fusion between autophagosomes and lysosomes, suggesting that PRRSV induced incomplete autophagy. This suppression caused the accumulation of autophagosomes which may serve as replication site to enhance PRRSV replication. It has been shown that NSP2 and NSP3 of arterivirus are two components of virus replication complex. We also found in our studies that NSP2 colocalized with LC3 in MARC-145 cells by performing confocal microscopy analysis and continuous density gradient centrifugation. Our studies presented here indicated that autophagy was activated during PRRSV infection and enhanced PRRSV replication in host cells by preventing autophagosome and lysosome fusion.
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, China.
authors: Ming-Xia
authors: MX
authors: Sun
authors: Li
authors: L
authors: Huang
authors: Rui
authors: R
authors: Wang
authors: Ya-Ling
authors: YL
authors: Yu
authors: Chen
authors: C
authors: Li
authors: Peng-Peng
authors: PP
authors: Li
authors: Xiao-Chun
authors: XC
authors: Hu
authors: Hong-Ping
authors: HP
authors: Hao
authors: Hassan A
authors: HA
authors: Ishag
authors: Xiang
authors: X
authors: Mao
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D055785:Gene Knockdown Techniques; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008561:Membrane Fusion / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010588:Phagosomes / Q000648:ultrastructure / Q000821:virology; D019318:Porcine Reproductive and Respiratory Syndrome / Q000473:pathology / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D034622:RNA Interference / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D013552:Swine / Q000821:virology*; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D008869:Microtubule-Associated Proteins; D017361:Viral Nonstructural Proteins; C025946:3-methyladenine; D000225:Adenine; D020123:Sirolimus