PMID- 25861024
OWN - NLM
STAT- MEDLINE
DCOM- 20160418
LR  - 20190223
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 4
DP  - 2015
TI  - Induction of microglia activation after infection with the non-neurotropic 
      A/CA/04/2009 H1N1 influenza virus.
PG  - e0124047
LID - 10.1371/journal.pone.0124047 [doi]
LID - e0124047
AB  - Although influenza is primarily a respiratory disease, it has been shown, in some 
      cases, to induce encephalitis, including people acutely infected with the 
      pandemic A/California/04/2009 (CA/09) H1N1 virus. Based on previous studies 
      showing that the highly pathogenic avian influenza (HPAI) A/Vietnam/1203/2004 
      H5N1 virus was neurotropic, induced CNS inflammation and a transient 
      parkinsonism, we examined the neurotropic and inflammatory potential of the CA/09 
      H1N1 virus in mice. Following intranasal inoculation, we found no evidence for 
      CA/09 H1N1 virus neurotropism in the enteric, peripheral or central nervous 
      systems. We did, however, observe a robust increase in microglial activity in the 
      brain characterized by an increase in the number of activated Iba-1-positive 
      microglia in the substantia nigra (SN) and the hippocampus, despite the absence 
      of virus in the brain. qPCR analysis in SN tissue showed that the induction of 
      microgliosis was preceded by reduced gene expression of the neurotrophic factors 
      bdnf, and gdnf and increases in the immune modulatory chemokine chemokine (C-C 
      motif) ligand 4 (ccl4). We also noted changes in the expression of transforming 
      growth factor-1 (tgfbeta1) in the SN starting at 7 days post-infection (dpi) that 
      was sustained through 21 dpi, coupled with increases in arginase-1 (arg1) and 
      csf1, M2 markers for microglia. Given that neuroinflammation contributes to 
      generation and progression of a number of neurodegenerative disorders, these 
      findings have significant implications as they highlight the possibility that 
      influenza and perhaps other non-neurotropic viruses can initiate inflammatory 
      signals via microglia activation in the brain and contribute to, but not 
      necessarily be the primary cause of, neurodegenerative disorders.
FAU - Sadasivan, Shankar
AU  - Sadasivan S
AD  - Department of Developmental Neurobiology, Saint Jude Children's Research 
      Hospital, Memphis, Tennessee, 38105, United States of America.
FAU - Zanin, Mark
AU  - Zanin M
AD  - Department of Infectious Diseases, Saint Jude Children's Research Hospital, 
      Memphis, Tennessee, 38105, United States of America.
FAU - O'Brien, Kevin
AU  - O'Brien K
AD  - Department of Infectious Diseases, Saint Jude Children's Research Hospital, 
      Memphis, Tennessee, 38105, United States of America.
FAU - Schultz-Cherry, Stacey
AU  - Schultz-Cherry S
AD  - Department of Infectious Diseases, Saint Jude Children's Research Hospital, 
      Memphis, Tennessee, 38105, United States of America.
FAU - Smeyne, Richard J
AU  - Smeyne RJ
AD  - Department of Developmental Neurobiology, Saint Jude Children's Research 
      Hospital, Memphis, Tennessee, 38105, United States of America.
LA  - eng
GR  - R01 NS075840/NS/NINDS NIH HHS/United States
GR  - NS075840-01/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150410
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chemokines)
RN  - 0 (Csf1r protein, mouse)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptors, Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 3.5.3.1 (Arg1 protein, mouse)
RN  - EC 3.5.3.1 (Arginase)
SB  - IM
MH  - Animals
MH  - Arginase/genetics
MH  - Blood-Brain Barrier
MH  - Chemokines/metabolism
MH  - Dentate Gyrus/pathology/virology
MH  - Encephalitis/etiology/pathology/virology
MH  - Female
MH  - Gene Expression
MH  - Influenza A Virus, H1N1 Subtype/classification/*pathogenicity
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/*pathology/virology
MH  - Nerve Growth Factors/metabolism
MH  - Orthomyxoviridae Infections/*etiology/*pathology/virology
MH  - Pars Compacta/pathology/virology
MH  - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics
MH  - Signal Transduction
MH  - T-Lymphocytes/pathology
MH  - Transforming Growth Factor beta1/genetics/metabolism
PMC - PMC4393251
COIS- Competing Interests: Richard Jay Smeyne, Ph.D. is a member of the PLOS ONE 
      Editorial Board; but understand that this does not alter the authors' adherence 
      to PLOS ONE Editorial policies and criteria.
EDAT- 2015/04/11 06:00
MHDA- 2016/04/19 06:00
PMCR- 2015/04/10
CRDT- 2015/04/11 06:00
PHST- 2014/09/18 00:00 [received]
PHST- 2015/02/26 00:00 [accepted]
PHST- 2015/04/11 06:00 [entrez]
PHST- 2015/04/11 06:00 [pubmed]
PHST- 2016/04/19 06:00 [medline]
PHST- 2015/04/10 00:00 [pmc-release]
AID - PONE-D-14-42094 [pii]
AID - 10.1371/journal.pone.0124047 [doi]
PST - epublish
SO  - PLoS One. 2015 Apr 10;10(4):e0124047. doi: 10.1371/journal.pone.0124047. 
      eCollection 2015.