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

Showa SP, Nyabadza F, Hove-Musekwa SD, Magombedze G - BMC Res Notes (2014)

Bottom Line: Model simulations and transient elasticity analysis of the viral levels to immune response parameters are used to compare the different immune mechanisms.On the contrary, we predicted the cell-mediated immune response to be always negatively correlated with viral levels.This study predicts that vaccine design efforts should also focus on stimulating killer T cells that target infected cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Mathematics, National University of Science and Technology, P,O, Box AC 939 Ascot, Bulawayo, Zimbabwe. showa.sarudzai@gmail.com.

ABSTRACT

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.

Show MeSH

Related in: MedlinePlus

Scatter plots with a quadratic fit between the viral levels and the infected cell killing efficiency of CTLs. The red line represent the quadratic fit and the small circles represent the data points (model outcomes). There is a negative relationship which can be best be explained by a quadratic function between the viral levels and the killing efficiency of infected cells by CTLs. The parameter values used are given in Table 1 and the initial conditions were .
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4221687&req=5

Fig7: Scatter plots with a quadratic fit between the viral levels and the infected cell killing efficiency of CTLs. The red line represent the quadratic fit and the small circles represent the data points (model outcomes). There is a negative relationship which can be best be explained by a quadratic function between the viral levels and the killing efficiency of infected cells by CTLs. The parameter values used are given in Table 1 and the initial conditions were .

Mentions: We also observed that the viral levels were most elastic to h2, the killing efficiency of CTLs during the late days of the infection and that the effect of this parameter was not dependent on the stage of the infection (all the elasticity values were negative in Figure 5). This means that an inverse relationship will be observed at all the stages of the infection. We randomly picked time point 100, to generate the scatter plot in Figure 7. The scatter plot in Figure 7 shows that there is a negative correlation between the killing efficiency h2 and the viral levels. We expect the same relationship at all time points.Figure 7


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

Showa SP, Nyabadza F, Hove-Musekwa SD, Magombedze G - BMC Res Notes (2014)

Scatter plots with a quadratic fit between the viral levels and the infected cell killing efficiency of CTLs. The red line represent the quadratic fit and the small circles represent the data points (model outcomes). There is a negative relationship which can be best be explained by a quadratic function between the viral levels and the killing efficiency of infected cells by CTLs. The parameter values used are given in Table 1 and the initial conditions were .
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4221687&req=5

Fig7: Scatter plots with a quadratic fit between the viral levels and the infected cell killing efficiency of CTLs. The red line represent the quadratic fit and the small circles represent the data points (model outcomes). There is a negative relationship which can be best be explained by a quadratic function between the viral levels and the killing efficiency of infected cells by CTLs. The parameter values used are given in Table 1 and the initial conditions were .
Mentions: We also observed that the viral levels were most elastic to h2, the killing efficiency of CTLs during the late days of the infection and that the effect of this parameter was not dependent on the stage of the infection (all the elasticity values were negative in Figure 5). This means that an inverse relationship will be observed at all the stages of the infection. We randomly picked time point 100, to generate the scatter plot in Figure 7. The scatter plot in Figure 7 shows that there is a negative correlation between the killing efficiency h2 and the viral levels. We expect the same relationship at all time points.Figure 7

Bottom Line: Model simulations and transient elasticity analysis of the viral levels to immune response parameters are used to compare the different immune mechanisms.On the contrary, we predicted the cell-mediated immune response to be always negatively correlated with viral levels.This study predicts that vaccine design efforts should also focus on stimulating killer T cells that target infected cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Mathematics, National University of Science and Technology, P,O, Box AC 939 Ascot, Bulawayo, Zimbabwe. showa.sarudzai@gmail.com.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus