Characterization of Nef expression in different brain regions of SIV-infected macaques.
<h4>Objective</h4>HIV-associated CNS dysfunction is a significant problem among people with HIV (PWH), who now live longer due to viral suppression from combined anti-retroviral therapy (ART). Over the course of infection, HIV generates toxic viral proteins and induces inflammatory cytok...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0241667 |
| _version_ | 1818398549781512192 |
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| author | Shadan S Yarandi Jake A Robinson Sarah Vakili Martina Donadoni Tricia H Burdo Ilker K Sariyer |
| author_facet | Shadan S Yarandi Jake A Robinson Sarah Vakili Martina Donadoni Tricia H Burdo Ilker K Sariyer |
| author_sort | Shadan S Yarandi |
| collection | DOAJ |
| description | <h4>Objective</h4>HIV-associated CNS dysfunction is a significant problem among people with HIV (PWH), who now live longer due to viral suppression from combined anti-retroviral therapy (ART). Over the course of infection, HIV generates toxic viral proteins and induces inflammatory cytokines that have toxic effects on neurons in the CNS. Among these viral proteins, HIV Nef has been found in neurons of postmortem brain specimens from PWH. However, the source of Nef and its impact on neuronal cell homeostasis are still elusive.<h4>Methods and results</h4>Here, in using a simian immunodeficiency virus (SIV) infected rhesus macaque model of neuroHIV, we find SIV Nef reactivity in the frontal cortex, hippocampus and cerebellum of SIV-infected animals using immunohistochemistry (IHC). Interestingly, SIV-infected macaques treated with ART also showed frequent Nef positive cells in the cerebellum and hippocampus. Using dual quantitative RNAscope and IHC, we observed cells that were positive for Nef, but were not for SIV RNA, suggesting that Nef protein is present in cells that are not actively infected with SIV. Using cell specific markers, we observed Nef protein in microglia/macrophages and astrocytes. Importantly, we also identified a number of NeuN-positive neurons, which are not permissive to SIV infection, but contained Nef protein. Further characterization of Nef-positive neurons showed caspase 3 activation, indicating late stage apoptosis in the CNS neurons.<h4>Conclusions</h4>Our results suggest that regardless of ART status, Nef is expressed in the brain of SIV infected macaques and may contribute to neurological complications seen in PWH. |
| first_indexed | 2024-12-14T07:06:33Z |
| format | Article |
| id | doaj.art-546b6b1a04294dcaaa4aedbd2fdd0af0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T07:06:33Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-546b6b1a04294dcaaa4aedbd2fdd0af02022-12-21T23:12:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-011511e024166710.1371/journal.pone.0241667Characterization of Nef expression in different brain regions of SIV-infected macaques.Shadan S YarandiJake A RobinsonSarah VakiliMartina DonadoniTricia H BurdoIlker K Sariyer<h4>Objective</h4>HIV-associated CNS dysfunction is a significant problem among people with HIV (PWH), who now live longer due to viral suppression from combined anti-retroviral therapy (ART). Over the course of infection, HIV generates toxic viral proteins and induces inflammatory cytokines that have toxic effects on neurons in the CNS. Among these viral proteins, HIV Nef has been found in neurons of postmortem brain specimens from PWH. However, the source of Nef and its impact on neuronal cell homeostasis are still elusive.<h4>Methods and results</h4>Here, in using a simian immunodeficiency virus (SIV) infected rhesus macaque model of neuroHIV, we find SIV Nef reactivity in the frontal cortex, hippocampus and cerebellum of SIV-infected animals using immunohistochemistry (IHC). Interestingly, SIV-infected macaques treated with ART also showed frequent Nef positive cells in the cerebellum and hippocampus. Using dual quantitative RNAscope and IHC, we observed cells that were positive for Nef, but were not for SIV RNA, suggesting that Nef protein is present in cells that are not actively infected with SIV. Using cell specific markers, we observed Nef protein in microglia/macrophages and astrocytes. Importantly, we also identified a number of NeuN-positive neurons, which are not permissive to SIV infection, but contained Nef protein. Further characterization of Nef-positive neurons showed caspase 3 activation, indicating late stage apoptosis in the CNS neurons.<h4>Conclusions</h4>Our results suggest that regardless of ART status, Nef is expressed in the brain of SIV infected macaques and may contribute to neurological complications seen in PWH.https://doi.org/10.1371/journal.pone.0241667 |
| spellingShingle | Shadan S Yarandi Jake A Robinson Sarah Vakili Martina Donadoni Tricia H Burdo Ilker K Sariyer Characterization of Nef expression in different brain regions of SIV-infected macaques. PLoS ONE |
| title | Characterization of Nef expression in different brain regions of SIV-infected macaques. |
| title_full | Characterization of Nef expression in different brain regions of SIV-infected macaques. |
| title_fullStr | Characterization of Nef expression in different brain regions of SIV-infected macaques. |
| title_full_unstemmed | Characterization of Nef expression in different brain regions of SIV-infected macaques. |
| title_short | Characterization of Nef expression in different brain regions of SIV-infected macaques. |
| title_sort | characterization of nef expression in different brain regions of siv infected macaques |
| url | https://doi.org/10.1371/journal.pone.0241667 |
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