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Monitoring HIV DNA and cellular activation markers in HIV-infected humanized mice under cART
BACKGROUND: The major obstacle to cure of HIV type-1 infection is the presence of the HIV reservoir, hidden from the immune system and insensitive to combined antiretroviral therapy (cART). Eradication approaches have been hindered by the difficulty for accurately monitoring its size in vivo, especi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296118/ https://www.ncbi.nlm.nih.gov/pubmed/30558630 http://dx.doi.org/10.1186/s12985-018-1101-9 |
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author | Rochat, Mary-Aude Schlaepfer, Erika Kuster, Stefan P. Li, Duo Audige, Annette Ivic, Sandra Fahrny, Audrey Speck, Roberto F. |
author_facet | Rochat, Mary-Aude Schlaepfer, Erika Kuster, Stefan P. Li, Duo Audige, Annette Ivic, Sandra Fahrny, Audrey Speck, Roberto F. |
author_sort | Rochat, Mary-Aude |
collection | PubMed |
description | BACKGROUND: The major obstacle to cure of HIV type-1 infection is the presence of the HIV reservoir, hidden from the immune system and insensitive to combined antiretroviral therapy (cART). Eradication approaches have been hindered by the difficulty for accurately monitoring its size in vivo, especially in the lymphoid organs. Humanized mouse models are a valuable tool for systematically assess the efficacy of therapeutic interventions in reducing the HIV reservoir. Nonetheless, persistence of the HIV reservoir over time, in the presence of cART, has yet to be analyzed in this in vivo model. FINDINGS: We found that the proviral DNA as well as the total DNA were very stable in the spleen and mesenteric lymph node irrespective of the length of cART. Notably, the amount of proviral DNA was very similar in the spleen and lymph node. Furthermore, we observed a correlation between the percentage of splenic human CD4+ T-cells with total HIV DNA, between the number of human CD38 + CD8+ T-cells in the spleen with the amount of integrated HIV DNA, and eventually between the hCD4/hCD8 ratio in the spleen with integrated as well as total HIV DNA implying that the CD8+ T cells influence the size of the HIV reservoir. CONCLUSIONS: Here, we demonstrated the stability of this reservoir in humanized mice irrespective of the length of cART, confirming the relevancy of this model for HIV latency eradication investigations. Notably, we also found correlates between the frequency of CD4+ T-cells, their activation status and viral parameters, which were analogous to the ones in HIV-infected patients. Thus, hu-mice represent a very valuable HIV latency model. |
format | Online Article Text |
id | pubmed-6296118 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-62961182018-12-18 Monitoring HIV DNA and cellular activation markers in HIV-infected humanized mice under cART Rochat, Mary-Aude Schlaepfer, Erika Kuster, Stefan P. Li, Duo Audige, Annette Ivic, Sandra Fahrny, Audrey Speck, Roberto F. Virol J Short Report BACKGROUND: The major obstacle to cure of HIV type-1 infection is the presence of the HIV reservoir, hidden from the immune system and insensitive to combined antiretroviral therapy (cART). Eradication approaches have been hindered by the difficulty for accurately monitoring its size in vivo, especially in the lymphoid organs. Humanized mouse models are a valuable tool for systematically assess the efficacy of therapeutic interventions in reducing the HIV reservoir. Nonetheless, persistence of the HIV reservoir over time, in the presence of cART, has yet to be analyzed in this in vivo model. FINDINGS: We found that the proviral DNA as well as the total DNA were very stable in the spleen and mesenteric lymph node irrespective of the length of cART. Notably, the amount of proviral DNA was very similar in the spleen and lymph node. Furthermore, we observed a correlation between the percentage of splenic human CD4+ T-cells with total HIV DNA, between the number of human CD38 + CD8+ T-cells in the spleen with the amount of integrated HIV DNA, and eventually between the hCD4/hCD8 ratio in the spleen with integrated as well as total HIV DNA implying that the CD8+ T cells influence the size of the HIV reservoir. CONCLUSIONS: Here, we demonstrated the stability of this reservoir in humanized mice irrespective of the length of cART, confirming the relevancy of this model for HIV latency eradication investigations. Notably, we also found correlates between the frequency of CD4+ T-cells, their activation status and viral parameters, which were analogous to the ones in HIV-infected patients. Thus, hu-mice represent a very valuable HIV latency model. BioMed Central 2018-12-17 /pmc/articles/PMC6296118/ /pubmed/30558630 http://dx.doi.org/10.1186/s12985-018-1101-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Short Report Rochat, Mary-Aude Schlaepfer, Erika Kuster, Stefan P. Li, Duo Audige, Annette Ivic, Sandra Fahrny, Audrey Speck, Roberto F. Monitoring HIV DNA and cellular activation markers in HIV-infected humanized mice under cART |
title | Monitoring HIV DNA and cellular activation markers in HIV-infected humanized mice under cART |
title_full | Monitoring HIV DNA and cellular activation markers in HIV-infected humanized mice under cART |
title_fullStr | Monitoring HIV DNA and cellular activation markers in HIV-infected humanized mice under cART |
title_full_unstemmed | Monitoring HIV DNA and cellular activation markers in HIV-infected humanized mice under cART |
title_short | Monitoring HIV DNA and cellular activation markers in HIV-infected humanized mice under cART |
title_sort | monitoring hiv dna and cellular activation markers in hiv-infected humanized mice under cart |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296118/ https://www.ncbi.nlm.nih.gov/pubmed/30558630 http://dx.doi.org/10.1186/s12985-018-1101-9 |
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