Abstract
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 (Aβ42) 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 Aβ42 peptide significantly attenuated these neuropathological responses. The inhibitory effects of Aβ42 peptide were also observed in an HSV-1-infected CV-1 cell-based viral plaque assay. The results suggest that soluble Aβ42 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.
| Original language | English |
|---|---|
| Pages (from-to) | 922-927 |
| Number of pages | 6 |
| Journal | NeuroReport |
| Volume | 21 |
| Issue number | 14 |
| DOIs | |
| State | Published - Oct 6 2010 |
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Keywords
- acyclovir
- acyloguanosine
- Alzheimer's disease
- amyloid-beta 42 peptide
- herpes simplex virus type-1
- inflammation
- innate immune response
- miRNA-146a
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Acyclovir or Aβ42 peptides attenuate HSV-1-induced miRNA-146a levels in human primary brain cells. / Lukiw, Walter J.; Cui, Jian Guo; Yuan, Li Yuan; Bhattacharjee, Partha S.; Corkern, Madelyn; Clement, Christian; Kammerman, Eli M.; Ball, M. J.; Zhao, Yuhai; Sullivan, Patrick M.; Hill, James M.
In: NeuroReport, Vol. 21, No. 14, 06.10.2010, p. 922-927.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Acyclovir or Aβ42 peptides attenuate HSV-1-induced miRNA-146a levels in human primary brain cells
AU - Lukiw, Walter J.
AU - Cui, Jian Guo
AU - Yuan, Li Yuan
AU - Bhattacharjee, Partha S.
AU - Corkern, Madelyn
AU - Clement, Christian
AU - Kammerman, Eli M.
AU - Ball, M. J.
AU - Zhao, Yuhai
AU - Sullivan, Patrick M.
AU - Hill, James M.
PY - 2010/10/6
Y1 - 2010/10/6
N2 - 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 (Aβ42) 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 Aβ42 peptide significantly attenuated these neuropathological responses. The inhibitory effects of Aβ42 peptide were also observed in an HSV-1-infected CV-1 cell-based viral plaque assay. The results suggest that soluble Aβ42 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.
AB - 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 (Aβ42) 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 Aβ42 peptide significantly attenuated these neuropathological responses. The inhibitory effects of Aβ42 peptide were also observed in an HSV-1-infected CV-1 cell-based viral plaque assay. The results suggest that soluble Aβ42 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.
KW - acyclovir
KW - acyloguanosine
KW - Alzheimer's disease
KW - amyloid-beta 42 peptide
KW - herpes simplex virus type-1
KW - inflammation
KW - innate immune response
KW - miRNA-146a
UR - http://www.scopus.com/inward/record.url?scp=77956406669&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956406669&partnerID=8YFLogxK
U2 - 10.1097/WNR.0b013e32833da51a
DO - 10.1097/WNR.0b013e32833da51a
M3 - Article
C2 - 20683212
AN - SCOPUS:77956406669
VL - 21
SP - 922
EP - 927
JO - NeuroReport
JF - NeuroReport
SN - 0959-4965
IS - 14
ER -