Acyclovir or Aβ42 peptides attenuate HSV-1-induced miRNA-146a levels in human primary brain cells.
Human brains harbor herpes simplex virus type-1 (HSV-1) DNA, which normally remains quiescent throughout many decades of life. HSV-1 is associated with viral encephalopathy and with the amyloid beta 42 (Abeta42) peptide-enriched lesions that characterize Alzheimer's disease neuropathology. Here we report that infection of human neuronal-glial cells in primary co-culture with HSV-1 induces an irregular hypertrophy of human neuronal-glial cell bodies, an induction of HSV-1 DNA polymerase, and an up-regulation of micro-RNA-146a associated with altered innate-immune responses. Presence of the antiviral acyclovir or soluble Abeta42 peptide significantly attenuated these neuropathological responses. The inhibitory effects of Abeta42 peptide were also observed in an HSV-1-infected CV-1 cell-based viral plaque assay. The results suggest that soluble Abeta42 peptide can invoke non-pathological and anti-viral effects through inactivation of an HSV-1 challenge to human brain cells by simple viral sequestration, viral destruction, or by complex neurogenetic mechanisms.
Lukiw
Walter J
WJ
LSU Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite 904, New Orleans, LA 70112-2272, USA. wlukiw@lsuhsc.edu
Cui
Jian Guo
JG
Yuan
Li Yuan
LY
Bhattacharjee
Partha S
PS
Corkern
Madelyn
M
Clement
Christian
C
Kammerman
Eli M
EM
Ball
M J
MJ
Zhao
Yuhai
Y
Sullivan
Patrick M
PM
Hill
James M
JM
D000212:Acyclovir / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D020803:Encephalitis, Herpes Simplex / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D010446:Peptide Fragments / Q000494:pharmacology*; D012367:RNA, Viral / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D016229:Amyloid beta-Peptides; D000998:Antiviral Agents; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D010446:Peptide Fragments; D012367:RNA, Viral; C075222:amyloid beta-protein (1-42); D000212:Acyclovir