title: Viroporin-mediated calcium-activated autophagy.
abstract: Autophagy is a cellular response activated by many pathogens, but the mechanism of activation is largely unknown. Recently we showed for the first time that rotavirus initiates the autophagy pathway through a calcium-mediated mechanism. Expression of the rotavirus-encoded NSP4, a pore-forming protein (viroporin), elicits the release of endoplasmic reticulum (ER) lumenal calcium into the cytoplasm of the infected cell. The increased cytoplasmic calcium activates a calcium signaling pathway involving calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) and 5' adenosine monophosphate-activated protein kinase (AMPK) to trigger autophagy. Rotavirus further manipulates autophagy membrane trafficking to transport viral ER-associated proteins to viroplasms, sites of viral genome replication and immature particle assembly. Transport of viral proteins to viroplasms is required for assembly of infectious virus. Thus, NSP4, a multifunctional viral protein known to regulate infectious particle assembly, also modulates membrane trafficking by orchestrating the activation of autophagy to benefit viral replication.
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: Sue E
authors: SE
authors: Crawford
authors: Mary K
authors: MK
authors: Estes
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D012401:Rotavirus / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D014118:Toxins, Biological / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D019065:Virus Assembly / Q000187:drug effects
chemical_list: D006023:Glycoproteins; C081369:NS28 protein, rotavirus; D014118:Toxins, Biological; D017361:Viral Nonstructural Proteins; D002118:Calcium
keywords: autophagy; calcium; kinase; stress; virus