title: Autophagy is involved in influenza A virus replication.
abstract: Autophagy is involved in the replication of viruses, especially those that perform RNA assembly on the surface of cytoplasmic membrane in host cells. However, little is known about the regulatory role of autophagy in influenza A virus replication. Using fluorescence and electron microscopy, we observed that autophagosomes can be induced and identified upon influenza A virus infection. The virus increased the amount of the autophagosome marker protein microtubule-associated protein light chain 3-II (LC3-II) and enhanced autophagic flux. When autophagy was pharmacologically inhibited by either 3-methylademine or wortmannin, the titers of influenza A virus were remarkably decreased. Viral reduction via autophagy inhibition was further confirmed by RNA interference, through which two different proteins required for autophagy were depleted. Noticeably, the compounds utilized had no marked effect on virus entry or cell viability, either of which might limit viral replication. Furthermore, alteration of cellular autophagy via pharmacological reagents or RNA interference impaired viral protein accumulation. Taken together, these findings indicate that autophagy is actively involved in influenza A virus replication.
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jiang
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fan
authors.forename: Xudong
authors.initials: X
authors.lastname: Hu
authors.forename: Jinguo
authors.initials: J
authors.lastname: Yan
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002470:Cell Survival; D004285:Dogs; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014779:Virus Replication; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C025946:3-methyladenine; D012313:RNA; D000225:Adenine; D000077191:Wortmannin