HSV-1 infection of human brain cells induces miRNA-146a and Alzheimer-type inflammatory signaling.
Herpes simplex virus type-1 (HSV-1) infection of human brain cells induces changes in gene expression favorable to the propagation of the infecting agent and detrimental to the function of the host cells. We report that infection of human primary neural cells with a high phenotypic reactivator HSV-1 (17syn+) induces upregulation of a brain-enriched microRNA (miRNA)-146a that is associated with proinflammatory signaling in stressed brain cells and Alzheimer's disease. Expression of cytoplasmic phospholipase A2, the inducible prostaglandin synthase cyclooxygenase-2, and the neuroinflammatory cytokine interleukin-1beta were each upregulated. A known miRNA-146a target in the brain, complement factor H, was downregulated. These data suggest a role for HSV-1-induced miRNA-146a in the evasion of HSV-1 from the complement system, and the activation of key elements of the arachidonic acid cascade known to contribute to Alzheimer-type neuropathological change.
LSU Neuroscience Center and Departments of Ophthalmology, Pharmacology, Microbiology, Genetics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
James M
JM
Hill
Yuhai
Y
Zhao
Christian
C
Clement
Donna M
DM
Neumann
Walter J
WJ
Lukiw
D001921:Brain / Q000166:cytology*; D002478:Cells, Cultured; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006561:Herpes Simplex / Q000473:pathology*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000821:virology; D054467:Phospholipases A2; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
D053583:Interleukin-1beta; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D017242:Complement Factor H; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D054467:Phospholipases A2