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Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection

HIV-1 replication within the central nervous system (CNS) impairs neurocognitive function and has the potential to establish persistent, compartmentalized viral reservoirs. The origins of HIV-1 detected in the CNS compartment are unknown, including whether cells within the cerebrospinal fluid (CSF)...

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Autores principales: Sharma, Vishakha, Creegan, Matthew, Tokarev, Andrey, Hsu, Denise, Slike, Bonnie M., Sacdalan, Carlo, Chan, Phillip, Spudich, Serena, Ananworanich, Jintanat, Eller, Michael A., Krebs, Shelly J., Vasan, Sandhya, Bolton, Diane L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683024/
https://www.ncbi.nlm.nih.gov/pubmed/34874976
http://dx.doi.org/10.1371/journal.ppat.1010105
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author Sharma, Vishakha
Creegan, Matthew
Tokarev, Andrey
Hsu, Denise
Slike, Bonnie M.
Sacdalan, Carlo
Chan, Phillip
Spudich, Serena
Ananworanich, Jintanat
Eller, Michael A.
Krebs, Shelly J.
Vasan, Sandhya
Bolton, Diane L.
author_facet Sharma, Vishakha
Creegan, Matthew
Tokarev, Andrey
Hsu, Denise
Slike, Bonnie M.
Sacdalan, Carlo
Chan, Phillip
Spudich, Serena
Ananworanich, Jintanat
Eller, Michael A.
Krebs, Shelly J.
Vasan, Sandhya
Bolton, Diane L.
author_sort Sharma, Vishakha
collection PubMed
description HIV-1 replication within the central nervous system (CNS) impairs neurocognitive function and has the potential to establish persistent, compartmentalized viral reservoirs. The origins of HIV-1 detected in the CNS compartment are unknown, including whether cells within the cerebrospinal fluid (CSF) produce virus. We measured viral RNA+ cells in CSF from acutely infected macaques longitudinally and people living with early stages of acute HIV-1. Active viral transcription (spliced viral RNA) was present in CSF CD4+ T cells as early as four weeks post-SHIV infection, and among all acute HIV-1 specimens (N = 6; Fiebig III/IV). Replication-inactive CD4+ T cell infection, indicated by unspliced viral RNA in the absence of spliced viral RNA, was even more prevalent, present in CSF of >50% macaques and human CSF at ~10-fold higher frequency than productive infection. Infection levels were similar between CSF and peripheral blood (and lymph nodes in macaques), indicating comparable T cell infection across these compartments. In addition, surface markers of activation were increased on CSF T cells and monocytes and correlated with CSF soluble markers of inflammation. These studies provide direct evidence of HIV-1 replication in CD4+ T cells and broad immune activation in peripheral blood and the CNS during acute infection, likely contributing to early neuroinflammation and reservoir seeding. Thus, early initiation of antiretroviral therapy may not be able to prevent establishment of CNS viral reservoirs and sources of long-term inflammation, important targets for HIV-1 cure and therapeutic strategies.
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spelling pubmed-86830242021-12-18 Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection Sharma, Vishakha Creegan, Matthew Tokarev, Andrey Hsu, Denise Slike, Bonnie M. Sacdalan, Carlo Chan, Phillip Spudich, Serena Ananworanich, Jintanat Eller, Michael A. Krebs, Shelly J. Vasan, Sandhya Bolton, Diane L. PLoS Pathog Research Article HIV-1 replication within the central nervous system (CNS) impairs neurocognitive function and has the potential to establish persistent, compartmentalized viral reservoirs. The origins of HIV-1 detected in the CNS compartment are unknown, including whether cells within the cerebrospinal fluid (CSF) produce virus. We measured viral RNA+ cells in CSF from acutely infected macaques longitudinally and people living with early stages of acute HIV-1. Active viral transcription (spliced viral RNA) was present in CSF CD4+ T cells as early as four weeks post-SHIV infection, and among all acute HIV-1 specimens (N = 6; Fiebig III/IV). Replication-inactive CD4+ T cell infection, indicated by unspliced viral RNA in the absence of spliced viral RNA, was even more prevalent, present in CSF of >50% macaques and human CSF at ~10-fold higher frequency than productive infection. Infection levels were similar between CSF and peripheral blood (and lymph nodes in macaques), indicating comparable T cell infection across these compartments. In addition, surface markers of activation were increased on CSF T cells and monocytes and correlated with CSF soluble markers of inflammation. These studies provide direct evidence of HIV-1 replication in CD4+ T cells and broad immune activation in peripheral blood and the CNS during acute infection, likely contributing to early neuroinflammation and reservoir seeding. Thus, early initiation of antiretroviral therapy may not be able to prevent establishment of CNS viral reservoirs and sources of long-term inflammation, important targets for HIV-1 cure and therapeutic strategies. Public Library of Science 2021-12-07 /pmc/articles/PMC8683024/ /pubmed/34874976 http://dx.doi.org/10.1371/journal.ppat.1010105 Text en © 2021 Sharma et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sharma, Vishakha
Creegan, Matthew
Tokarev, Andrey
Hsu, Denise
Slike, Bonnie M.
Sacdalan, Carlo
Chan, Phillip
Spudich, Serena
Ananworanich, Jintanat
Eller, Michael A.
Krebs, Shelly J.
Vasan, Sandhya
Bolton, Diane L.
Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection
title Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection
title_full Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection
title_fullStr Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection
title_full_unstemmed Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection
title_short Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection
title_sort cerebrospinal fluid cd4+ t cell infection in humans and macaques during acute hiv-1 and shiv infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683024/
https://www.ncbi.nlm.nih.gov/pubmed/34874976
http://dx.doi.org/10.1371/journal.ppat.1010105
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