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Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model

BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs) infected with simian immunodeficiency virus (SIV) have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. MET...

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Autores principales: Chen, Song, Lai, Chunhui, Wu, Xiaoxiang, Lu, Yaozheng, Han, Daishu, Guo, Weizhong, Fu, Linchun, Andrieu, Jean-Marie, Lu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151272/
https://www.ncbi.nlm.nih.gov/pubmed/21850259
http://dx.doi.org/10.1371/journal.pone.0023177
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author Chen, Song
Lai, Chunhui
Wu, Xiaoxiang
Lu, Yaozheng
Han, Daishu
Guo, Weizhong
Fu, Linchun
Andrieu, Jean-Marie
Lu, Wei
author_facet Chen, Song
Lai, Chunhui
Wu, Xiaoxiang
Lu, Yaozheng
Han, Daishu
Guo, Weizhong
Fu, Linchun
Andrieu, Jean-Marie
Lu, Wei
author_sort Chen, Song
collection PubMed
description BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs) infected with simian immunodeficiency virus (SIV) have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL FINDINGS: By randomizing 150 (78 male and 72 female) Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group) challenged with intrarectal (ir) SIVmac239, intravenous (iv) SIVmac239, or iv SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1–2 weeks. Plasma viral load (VL) peaked at weeks 1–2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (ir or iv)-infected than in SIVmac251 (iv)-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68). The rates of progression to AIDS or death were more rapid in SIVmac239 (ir or iv)-infected than in SIVmac251 (iv)-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with ir or iv SIVmac239. The variability (standard deviation) in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (ir or iv) than in those infected with SIVmac251 (iv), allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies.
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spelling pubmed-31512722011-08-17 Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model Chen, Song Lai, Chunhui Wu, Xiaoxiang Lu, Yaozheng Han, Daishu Guo, Weizhong Fu, Linchun Andrieu, Jean-Marie Lu, Wei PLoS One Research Article BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs) infected with simian immunodeficiency virus (SIV) have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL FINDINGS: By randomizing 150 (78 male and 72 female) Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group) challenged with intrarectal (ir) SIVmac239, intravenous (iv) SIVmac239, or iv SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1–2 weeks. Plasma viral load (VL) peaked at weeks 1–2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (ir or iv)-infected than in SIVmac251 (iv)-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68). The rates of progression to AIDS or death were more rapid in SIVmac239 (ir or iv)-infected than in SIVmac251 (iv)-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with ir or iv SIVmac239. The variability (standard deviation) in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (ir or iv) than in those infected with SIVmac251 (iv), allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies. Public Library of Science 2011-08-05 /pmc/articles/PMC3151272/ /pubmed/21850259 http://dx.doi.org/10.1371/journal.pone.0023177 Text en Chen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chen, Song
Lai, Chunhui
Wu, Xiaoxiang
Lu, Yaozheng
Han, Daishu
Guo, Weizhong
Fu, Linchun
Andrieu, Jean-Marie
Lu, Wei
Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model
title Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model
title_full Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model
title_fullStr Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model
title_full_unstemmed Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model
title_short Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model
title_sort variability of bio-clinical parameters in chinese-origin rhesus macaques infected with simian immunodeficiency virus: a nonhuman primate aids model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151272/
https://www.ncbi.nlm.nih.gov/pubmed/21850259
http://dx.doi.org/10.1371/journal.pone.0023177
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