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Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection

The twin pandemics of opioid abuse and HIV infection can have devastating effects on physiological systems, including on the brain. Our previous work found that morphine increased the viral reservoir in the brains of treated SIV-infected macaques. In this study, we investigated the interaction of mo...

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Autores principales: Fox, Howard S., Niu, Meng, Morsey, Brenda M., Lamberty, Benjamin G., Emanuel, Katy, Periyasamy, Palsamy, Callen, Shannon, Acharya, Arpan, Kubik, Gregory, Eudy, James, Guda, Chittibabu, Dyavar, Shetty Ravi, Fletcher, Courtney V., Byrareddy, Siddappa N., Buch, Shilpa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709286/
https://www.ncbi.nlm.nih.gov/pubmed/36466814
http://dx.doi.org/10.3389/fimmu.2022.1012884
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author Fox, Howard S.
Niu, Meng
Morsey, Brenda M.
Lamberty, Benjamin G.
Emanuel, Katy
Periyasamy, Palsamy
Callen, Shannon
Acharya, Arpan
Kubik, Gregory
Eudy, James
Guda, Chittibabu
Dyavar, Shetty Ravi
Fletcher, Courtney V.
Byrareddy, Siddappa N.
Buch, Shilpa
author_facet Fox, Howard S.
Niu, Meng
Morsey, Brenda M.
Lamberty, Benjamin G.
Emanuel, Katy
Periyasamy, Palsamy
Callen, Shannon
Acharya, Arpan
Kubik, Gregory
Eudy, James
Guda, Chittibabu
Dyavar, Shetty Ravi
Fletcher, Courtney V.
Byrareddy, Siddappa N.
Buch, Shilpa
author_sort Fox, Howard S.
collection PubMed
description The twin pandemics of opioid abuse and HIV infection can have devastating effects on physiological systems, including on the brain. Our previous work found that morphine increased the viral reservoir in the brains of treated SIV-infected macaques. In this study, we investigated the interaction of morphine and SIV to identify novel host-specific targets using a multimodal approach. We probed systemic parameters and performed single-cell examination of the targets for infection in the brain, microglia and macrophages. Morphine treatment created an immunosuppressive environment, blunting initial responses to infection, which persisted during antiretroviral treatment. Antiretroviral drug concentrations and penetration into the cerebrospinal fluid and brain were unchanged by morphine treatment. Interestingly, the transcriptional signature of both microglia and brain macrophages was transformed to one of a neurodegenerative phenotype. Notably, the expression of osteopontin, a pleiotropic cytokine, was significantly elevated in microglia. This was especially notable in the white matter, which is also dually affected by HIV and opioids. Increased osteopontin expression was linked to numerous HIV neuropathogenic mechanisms, including those that can maintain a viral reservoir. The opioid morphine is detrimental to SIV/HIV infection, especially in the brain.
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spelling pubmed-97092862022-12-01 Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection Fox, Howard S. Niu, Meng Morsey, Brenda M. Lamberty, Benjamin G. Emanuel, Katy Periyasamy, Palsamy Callen, Shannon Acharya, Arpan Kubik, Gregory Eudy, James Guda, Chittibabu Dyavar, Shetty Ravi Fletcher, Courtney V. Byrareddy, Siddappa N. Buch, Shilpa Front Immunol Immunology The twin pandemics of opioid abuse and HIV infection can have devastating effects on physiological systems, including on the brain. Our previous work found that morphine increased the viral reservoir in the brains of treated SIV-infected macaques. In this study, we investigated the interaction of morphine and SIV to identify novel host-specific targets using a multimodal approach. We probed systemic parameters and performed single-cell examination of the targets for infection in the brain, microglia and macrophages. Morphine treatment created an immunosuppressive environment, blunting initial responses to infection, which persisted during antiretroviral treatment. Antiretroviral drug concentrations and penetration into the cerebrospinal fluid and brain were unchanged by morphine treatment. Interestingly, the transcriptional signature of both microglia and brain macrophages was transformed to one of a neurodegenerative phenotype. Notably, the expression of osteopontin, a pleiotropic cytokine, was significantly elevated in microglia. This was especially notable in the white matter, which is also dually affected by HIV and opioids. Increased osteopontin expression was linked to numerous HIV neuropathogenic mechanisms, including those that can maintain a viral reservoir. The opioid morphine is detrimental to SIV/HIV infection, especially in the brain. Frontiers Media S.A. 2022-11-16 /pmc/articles/PMC9709286/ /pubmed/36466814 http://dx.doi.org/10.3389/fimmu.2022.1012884 Text en Copyright © 2022 Fox, Niu, Morsey, Lamberty, Emanuel, Periyasamy, Callen, Acharya, Kubik, Eudy, Guda, Dyavar, Fletcher, Byrareddy and Buch https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Fox, Howard S.
Niu, Meng
Morsey, Brenda M.
Lamberty, Benjamin G.
Emanuel, Katy
Periyasamy, Palsamy
Callen, Shannon
Acharya, Arpan
Kubik, Gregory
Eudy, James
Guda, Chittibabu
Dyavar, Shetty Ravi
Fletcher, Courtney V.
Byrareddy, Siddappa N.
Buch, Shilpa
Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection
title Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection
title_full Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection
title_fullStr Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection
title_full_unstemmed Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection
title_short Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection
title_sort morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in siv infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709286/
https://www.ncbi.nlm.nih.gov/pubmed/36466814
http://dx.doi.org/10.3389/fimmu.2022.1012884
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