Cargando…

A comparison of elasticities of viral levels to specific immune response mechanisms in human immunodeficiency virus infection

BACKGROUND: The presence of an asymptomatic phase in an HIV infection indicates that the immune system can partially control the infection. Determining the immune mechanisms that contribute significantly to the partial control of the infection enhance the HIV infection intervention strategies and is...

Descripción completa

Detalles Bibliográficos
Autores principales: Showa, Sarudzai P, Nyabadza, Farai, Hove-Musekwa, Senelani D, Magombedze, Gesham
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221687/
https://www.ncbi.nlm.nih.gov/pubmed/25331717
http://dx.doi.org/10.1186/1756-0500-7-737
_version_ 1782342915384672256
author Showa, Sarudzai P
Nyabadza, Farai
Hove-Musekwa, Senelani D
Magombedze, Gesham
author_facet Showa, Sarudzai P
Nyabadza, Farai
Hove-Musekwa, Senelani D
Magombedze, Gesham
author_sort Showa, Sarudzai P
collection PubMed
description BACKGROUND: The presence of an asymptomatic phase in an HIV infection indicates that the immune system can partially control the infection. Determining the immune mechanisms that contribute significantly to the partial control of the infection enhance the HIV infection intervention strategies and is important in vaccine development. Towards this goal, a discrete time HIV model, which incorporates the life cycle aspects of the virus, the antibody (humoral) response and the cell-mediated immune response is formulated to determine immune system components that are most efficient in controlling viral levels. Ecological relationships are used to model the interplay between the immune system components and the HIV pathogen. Model simulations and transient elasticity analysis of the viral levels to immune response parameters are used to compare the different immune mechanisms. RESULTS: It is shown that cell-mediated immune response is more effective in controlling the viral levels than the antibody response. Killing of infected cells is shown to be crucial in controlling the viral levels. Our results show a negative correlation between the antibody response and the viral levels in the early stages of the infection, but we predicted this immune mechanism to be positively correlated with the viral levels in the late stage of the infection. A result that suggests lack of relevance of antibody response with infection progression. On the contrary, we predicted the cell-mediated immune response to be always negatively correlated with viral levels. CONCLUSION: Neutralizing antibodies can only control the viral levels in the early days of the HIV infection whereas cell-mediated immune response is beneficial during all the stages of the infection. This study predicts that vaccine design efforts should also focus on stimulating killer T cells that target infected cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1756-0500-7-737) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4221687
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-42216872014-11-07 A comparison of elasticities of viral levels to specific immune response mechanisms in human immunodeficiency virus infection Showa, Sarudzai P Nyabadza, Farai Hove-Musekwa, Senelani D Magombedze, Gesham BMC Res Notes Research Article BACKGROUND: The presence of an asymptomatic phase in an HIV infection indicates that the immune system can partially control the infection. Determining the immune mechanisms that contribute significantly to the partial control of the infection enhance the HIV infection intervention strategies and is important in vaccine development. Towards this goal, a discrete time HIV model, which incorporates the life cycle aspects of the virus, the antibody (humoral) response and the cell-mediated immune response is formulated to determine immune system components that are most efficient in controlling viral levels. Ecological relationships are used to model the interplay between the immune system components and the HIV pathogen. Model simulations and transient elasticity analysis of the viral levels to immune response parameters are used to compare the different immune mechanisms. RESULTS: It is shown that cell-mediated immune response is more effective in controlling the viral levels than the antibody response. Killing of infected cells is shown to be crucial in controlling the viral levels. Our results show a negative correlation between the antibody response and the viral levels in the early stages of the infection, but we predicted this immune mechanism to be positively correlated with the viral levels in the late stage of the infection. A result that suggests lack of relevance of antibody response with infection progression. On the contrary, we predicted the cell-mediated immune response to be always negatively correlated with viral levels. CONCLUSION: Neutralizing antibodies can only control the viral levels in the early days of the HIV infection whereas cell-mediated immune response is beneficial during all the stages of the infection. This study predicts that vaccine design efforts should also focus on stimulating killer T cells that target infected cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1756-0500-7-737) contains supplementary material, which is available to authorized users. BioMed Central 2014-10-20 /pmc/articles/PMC4221687/ /pubmed/25331717 http://dx.doi.org/10.1186/1756-0500-7-737 Text en © Showa et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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 Article
Showa, Sarudzai P
Nyabadza, Farai
Hove-Musekwa, Senelani D
Magombedze, Gesham
A comparison of elasticities of viral levels to specific immune response mechanisms in human immunodeficiency virus infection
title A comparison of elasticities of viral levels to specific immune response mechanisms in human immunodeficiency virus infection
title_full A comparison of elasticities of viral levels to specific immune response mechanisms in human immunodeficiency virus infection
title_fullStr A comparison of elasticities of viral levels to specific immune response mechanisms in human immunodeficiency virus infection
title_full_unstemmed A comparison of elasticities of viral levels to specific immune response mechanisms in human immunodeficiency virus infection
title_short A comparison of elasticities of viral levels to specific immune response mechanisms in human immunodeficiency virus infection
title_sort comparison of elasticities of viral levels to specific immune response mechanisms in human immunodeficiency virus infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221687/
https://www.ncbi.nlm.nih.gov/pubmed/25331717
http://dx.doi.org/10.1186/1756-0500-7-737
work_keys_str_mv AT showasarudzaip acomparisonofelasticitiesofvirallevelstospecificimmuneresponsemechanismsinhumanimmunodeficiencyvirusinfection
AT nyabadzafarai acomparisonofelasticitiesofvirallevelstospecificimmuneresponsemechanismsinhumanimmunodeficiencyvirusinfection
AT hovemusekwasenelanid acomparisonofelasticitiesofvirallevelstospecificimmuneresponsemechanismsinhumanimmunodeficiencyvirusinfection
AT magombedzegesham acomparisonofelasticitiesofvirallevelstospecificimmuneresponsemechanismsinhumanimmunodeficiencyvirusinfection
AT showasarudzaip comparisonofelasticitiesofvirallevelstospecificimmuneresponsemechanismsinhumanimmunodeficiencyvirusinfection
AT nyabadzafarai comparisonofelasticitiesofvirallevelstospecificimmuneresponsemechanismsinhumanimmunodeficiencyvirusinfection
AT hovemusekwasenelanid comparisonofelasticitiesofvirallevelstospecificimmuneresponsemechanismsinhumanimmunodeficiencyvirusinfection
AT magombedzegesham comparisonofelasticitiesofvirallevelstospecificimmuneresponsemechanismsinhumanimmunodeficiencyvirusinfection