Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus.
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/...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4393251?pdf=render |
| _version_ | 1818997703331282944 |
|---|---|
| author | Shankar Sadasivan Mark Zanin Kevin O'Brien Stacey Schultz-Cherry Richard J Smeyne |
| author_facet | Shankar Sadasivan Mark Zanin Kevin O'Brien Stacey Schultz-Cherry Richard J Smeyne |
| author_sort | Shankar Sadasivan |
| collection | DOAJ |
| description | 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 (tgfβ1) 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. |
| first_indexed | 2024-12-20T21:49:51Z |
| format | Article |
| id | doaj.art-762ccf93e7d04a838e53d34b1120f16f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T21:49:51Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-762ccf93e7d04a838e53d34b1120f16f2022-12-21T19:25:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012404710.1371/journal.pone.0124047Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus.Shankar SadasivanMark ZaninKevin O'BrienStacey Schultz-CherryRichard J SmeyneAlthough 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 (tgfβ1) 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.http://europepmc.org/articles/PMC4393251?pdf=render |
| spellingShingle | Shankar Sadasivan Mark Zanin Kevin O'Brien Stacey Schultz-Cherry Richard J Smeyne Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus. PLoS ONE |
| title | Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus. |
| title_full | Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus. |
| title_fullStr | Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus. |
| title_full_unstemmed | Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus. |
| title_short | Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus. |
| title_sort | induction of microglia activation after infection with the non neurotropic a ca 04 2009 h1n1 influenza virus |
| url | http://europepmc.org/articles/PMC4393251?pdf=render |
| work_keys_str_mv | AT shankarsadasivan inductionofmicrogliaactivationafterinfectionwiththenonneurotropicaca042009h1n1influenzavirus AT markzanin inductionofmicrogliaactivationafterinfectionwiththenonneurotropicaca042009h1n1influenzavirus AT kevinobrien inductionofmicrogliaactivationafterinfectionwiththenonneurotropicaca042009h1n1influenzavirus AT staceyschultzcherry inductionofmicrogliaactivationafterinfectionwiththenonneurotropicaca042009h1n1influenzavirus AT richardjsmeyne inductionofmicrogliaactivationafterinfectionwiththenonneurotropicaca042009h1n1influenzavirus |