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Low level expression of the Mitochondrial Antiviral Signaling protein (MAVS) associated with long-term nonprogression in SIV-infected rhesus macaques

BACKGROUND: Abnormally increased immune activation is one of the main pathological features of acquired immunodeficiency syndrome (AIDS). This study aimed to determine whether long-term nonprogression (LTNP) suppresses the upregulation of immune activation and to elucidate the mechanisms whereby the...

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Autores principales: Zhang, Miaomiao, Fu, Zhuotao, Chen, Jiantao, Zhu, Boqiang, Cheng, Ye, Fu, Linchun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192151/
https://www.ncbi.nlm.nih.gov/pubmed/30326919
http://dx.doi.org/10.1186/s12985-018-1069-5
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author Zhang, Miaomiao
Fu, Zhuotao
Chen, Jiantao
Zhu, Boqiang
Cheng, Ye
Fu, Linchun
author_facet Zhang, Miaomiao
Fu, Zhuotao
Chen, Jiantao
Zhu, Boqiang
Cheng, Ye
Fu, Linchun
author_sort Zhang, Miaomiao
collection PubMed
description BACKGROUND: Abnormally increased immune activation is one of the main pathological features of acquired immunodeficiency syndrome (AIDS). This study aimed to determine whether long-term nonprogression (LTNP) suppresses the upregulation of immune activation and to elucidate the mechanisms whereby the LTNP state is maintained. METHODS: For this study we selected 4 rhesus macaques(RMs) infected with simian immunodeficiency virus (SIV) that were long-term nonprogressors (LTNP); for comparison we chose 4 healthy RMs that were seronegative for SIV (hereafter referred to as the Control group), and 4 progressing infection (Progressive group) SIV RMs. We observed these animals for 6 months without intervention and explored the immunological and pathological differences among the 3 groups. A series of immune activation and inflammation markers—such as C- C chemokine receptor type 5 (CCR5), beta 2- microglobulin (β2-MG), Human Leukocyte Antigen - antigen D Related (HLA-DR), CD38, the levels of microbial translocation (LPS -binding protein), and MAVS—and histological features were monitored during this period. RESULTS: Both SIV RNA and SIV DNA in the plasma and lymph nodes (LNs) of the LTNP group were at significantly lower levels than those of the Progressive group (P < 0.05). The CD4/CD8 ratio and CD4 cell count and proportion in the LTNP group were between those of the Progressive and Control groups (P < 0.05): that is, they were higher than in the Progressive group and lower than in the Control group. The LTNP macaques manifested slow progression and decreased immune activation and inflammation; they also had lower levels of CCR5, LPS-binding protein, and β2-MG than the Progressive RMs (P < 0.05). Activation of LTNP in both CD4+ and CD8+ T cells was significantly lower than in the Progressive group and closer to that in the Control group. The histological features of the LTNP macaques were also closer to those of the Control group, even though they had been infected with SIV 4 years earlier. These data point to low viral replication in the LTNP macaques but it is not static. The expression of MAVS in peripheral blood and LNs was lower in the LTNP group than that in the Progressive group (P < 0.01), and MAVS was positively correlated with SIV DNA in LNs (P < 0.05). This may reflect the low activation of T lymphocytes. It was speculated that MAVS may be the link between innate and acquired antiviral immunity in SIV infection. CONCLUSIONS: The LTNP RMs in our study were in a relatively stable state of low activation and inflammation, some biological progression with no disease events. This may have been associated with their low levels of the mitochondrial antiviral signaling protein (MAVS).
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spelling pubmed-61921512018-10-22 Low level expression of the Mitochondrial Antiviral Signaling protein (MAVS) associated with long-term nonprogression in SIV-infected rhesus macaques Zhang, Miaomiao Fu, Zhuotao Chen, Jiantao Zhu, Boqiang Cheng, Ye Fu, Linchun Virol J Research BACKGROUND: Abnormally increased immune activation is one of the main pathological features of acquired immunodeficiency syndrome (AIDS). This study aimed to determine whether long-term nonprogression (LTNP) suppresses the upregulation of immune activation and to elucidate the mechanisms whereby the LTNP state is maintained. METHODS: For this study we selected 4 rhesus macaques(RMs) infected with simian immunodeficiency virus (SIV) that were long-term nonprogressors (LTNP); for comparison we chose 4 healthy RMs that were seronegative for SIV (hereafter referred to as the Control group), and 4 progressing infection (Progressive group) SIV RMs. We observed these animals for 6 months without intervention and explored the immunological and pathological differences among the 3 groups. A series of immune activation and inflammation markers—such as C- C chemokine receptor type 5 (CCR5), beta 2- microglobulin (β2-MG), Human Leukocyte Antigen - antigen D Related (HLA-DR), CD38, the levels of microbial translocation (LPS -binding protein), and MAVS—and histological features were monitored during this period. RESULTS: Both SIV RNA and SIV DNA in the plasma and lymph nodes (LNs) of the LTNP group were at significantly lower levels than those of the Progressive group (P < 0.05). The CD4/CD8 ratio and CD4 cell count and proportion in the LTNP group were between those of the Progressive and Control groups (P < 0.05): that is, they were higher than in the Progressive group and lower than in the Control group. The LTNP macaques manifested slow progression and decreased immune activation and inflammation; they also had lower levels of CCR5, LPS-binding protein, and β2-MG than the Progressive RMs (P < 0.05). Activation of LTNP in both CD4+ and CD8+ T cells was significantly lower than in the Progressive group and closer to that in the Control group. The histological features of the LTNP macaques were also closer to those of the Control group, even though they had been infected with SIV 4 years earlier. These data point to low viral replication in the LTNP macaques but it is not static. The expression of MAVS in peripheral blood and LNs was lower in the LTNP group than that in the Progressive group (P < 0.01), and MAVS was positively correlated with SIV DNA in LNs (P < 0.05). This may reflect the low activation of T lymphocytes. It was speculated that MAVS may be the link between innate and acquired antiviral immunity in SIV infection. CONCLUSIONS: The LTNP RMs in our study were in a relatively stable state of low activation and inflammation, some biological progression with no disease events. This may have been associated with their low levels of the mitochondrial antiviral signaling protein (MAVS). BioMed Central 2018-10-16 /pmc/articles/PMC6192151/ /pubmed/30326919 http://dx.doi.org/10.1186/s12985-018-1069-5 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 Research
Zhang, Miaomiao
Fu, Zhuotao
Chen, Jiantao
Zhu, Boqiang
Cheng, Ye
Fu, Linchun
Low level expression of the Mitochondrial Antiviral Signaling protein (MAVS) associated with long-term nonprogression in SIV-infected rhesus macaques
title Low level expression of the Mitochondrial Antiviral Signaling protein (MAVS) associated with long-term nonprogression in SIV-infected rhesus macaques
title_full Low level expression of the Mitochondrial Antiviral Signaling protein (MAVS) associated with long-term nonprogression in SIV-infected rhesus macaques
title_fullStr Low level expression of the Mitochondrial Antiviral Signaling protein (MAVS) associated with long-term nonprogression in SIV-infected rhesus macaques
title_full_unstemmed Low level expression of the Mitochondrial Antiviral Signaling protein (MAVS) associated with long-term nonprogression in SIV-infected rhesus macaques
title_short Low level expression of the Mitochondrial Antiviral Signaling protein (MAVS) associated with long-term nonprogression in SIV-infected rhesus macaques
title_sort low level expression of the mitochondrial antiviral signaling protein (mavs) associated with long-term nonprogression in siv-infected rhesus macaques
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192151/
https://www.ncbi.nlm.nih.gov/pubmed/30326919
http://dx.doi.org/10.1186/s12985-018-1069-5
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