Limits...
HIV-1 Dual Infected LTNP-EC Patients Developed an Unexpected Antibody Cross-Neutralizing Activity.

Pernas M, Sanchez-Merino V, Casado C, Merino-Mansilla A, Olivares I, Yuste E, Lopez-Galindez C - PLoS ONE (2015)

Bottom Line: Our results showed an improved neutralization breadth in DI LTNP-EC patients when compared with matched LTNP single-infected patients.We found a positive correlation between neutralization breadth and diversity within the viral quasispecies.This correlation could explain why a group of LTNP-EC patients developed a broad neutralizing response despite having undetectable levels of viremia.

View Article: PubMed Central - PubMed

Affiliation: Centro Nacional de MicrobiologĂ­a (CNM), Instituto de Salud Carlos III, Majadahonda, Madrid 28220, Spain.

ABSTRACT
This study evaluated the neutralization breadth in dually infected (DI) HIV-1 long-term non-progressor elite controller patients (LTNP-EC) using a representative minipanel of 6 viruses from 5 different subtypes. Our results showed an improved neutralization breadth in DI LTNP-EC patients when compared with matched LTNP single-infected patients. The role of viral diversity in neutralization was estimated with the Shannon Entropy and the p-distance in viral quasispecies. We found a positive correlation between neutralization breadth and diversity within the viral quasispecies. This correlation could explain why a group of LTNP-EC patients developed a broad neutralizing response despite having undetectable levels of viremia.

No MeSH data available.


Related in: MedlinePlus

Correlation between clinical data and genetic diversity parameters with heterologous NAb response.Association between viral load (panel A), Cd4+T cells (panel B), years after infection (panel C), Shannon Entropy (panel D), p-distance (panel E), number of synonymous mutations (ds) (panel F), number of non-synonymous mutations (dn) (panel G) and the ratio ds/dn (Panel H) and number of cross-reactive subtypes was calculated. Median of the different clinical data and the genetic parameters for each patient (y axis) was plotted against the number of subtypes neutralized by each the patients (x axis). Patients are identified by the following symbols. LTNP 17 (blue triangle), LTNP 2 (purple triangle), LTNP 20 (green triangle), LTNP 21 (grey triangle), LTNP 3 (orange triangle), MDM (green circle), LTNP-5 (yellow circle), and LTNP 15 (red circle). Correlation between parameters was calculated by linear regression with a 95% of confidence using GraphPad Prism V 4.0 software. For the comparison of the values, a statistical analysis was performed with the non-parametric 2-tailed Mann-Whitney U test with a restrictive significance at the 95% using GraphPad Prism V 4.0 software.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4530867&req=5

pone.0134054.g003: Correlation between clinical data and genetic diversity parameters with heterologous NAb response.Association between viral load (panel A), Cd4+T cells (panel B), years after infection (panel C), Shannon Entropy (panel D), p-distance (panel E), number of synonymous mutations (ds) (panel F), number of non-synonymous mutations (dn) (panel G) and the ratio ds/dn (Panel H) and number of cross-reactive subtypes was calculated. Median of the different clinical data and the genetic parameters for each patient (y axis) was plotted against the number of subtypes neutralized by each the patients (x axis). Patients are identified by the following symbols. LTNP 17 (blue triangle), LTNP 2 (purple triangle), LTNP 20 (green triangle), LTNP 21 (grey triangle), LTNP 3 (orange triangle), MDM (green circle), LTNP-5 (yellow circle), and LTNP 15 (red circle). Correlation between parameters was calculated by linear regression with a 95% of confidence using GraphPad Prism V 4.0 software. For the comparison of the values, a statistical analysis was performed with the non-parametric 2-tailed Mann-Whitney U test with a restrictive significance at the 95% using GraphPad Prism V 4.0 software.

Mentions: Viral load values and CD4+ T cell counts were recorded during the patient clinical follow-up and as shown in Fig 3A and 3B, there was no association between these clinical data nor between years after first HIV+ detection (Fig 3C) and the number of cross-reactive subtypes. In contrast, a positive correlation between viral diversity, measured as Shannon Entropy (p = 0.01, r2 = 0.66) (Fig 3D), or p-distance (p = 0.01, r2 = 0.51) (Fig 3E) and the number of cross-reactive subtypes was observed. This result suggested that viral diversity has contributed to the increase of Nab breadth in DI patients. This diversity was more contributed by the synonymous (Fig 3F) than to the non-synonymous changes (Fig 3G) but it was not significant in ds/dn ratios. In summary all these analysis supported a clear contribution of viral diversity, because of DI, to the neutralization breath in these patients.


HIV-1 Dual Infected LTNP-EC Patients Developed an Unexpected Antibody Cross-Neutralizing Activity.

Pernas M, Sanchez-Merino V, Casado C, Merino-Mansilla A, Olivares I, Yuste E, Lopez-Galindez C - PLoS ONE (2015)

Correlation between clinical data and genetic diversity parameters with heterologous NAb response.Association between viral load (panel A), Cd4+T cells (panel B), years after infection (panel C), Shannon Entropy (panel D), p-distance (panel E), number of synonymous mutations (ds) (panel F), number of non-synonymous mutations (dn) (panel G) and the ratio ds/dn (Panel H) and number of cross-reactive subtypes was calculated. Median of the different clinical data and the genetic parameters for each patient (y axis) was plotted against the number of subtypes neutralized by each the patients (x axis). Patients are identified by the following symbols. LTNP 17 (blue triangle), LTNP 2 (purple triangle), LTNP 20 (green triangle), LTNP 21 (grey triangle), LTNP 3 (orange triangle), MDM (green circle), LTNP-5 (yellow circle), and LTNP 15 (red circle). Correlation between parameters was calculated by linear regression with a 95% of confidence using GraphPad Prism V 4.0 software. For the comparison of the values, a statistical analysis was performed with the non-parametric 2-tailed Mann-Whitney U test with a restrictive significance at the 95% using GraphPad Prism V 4.0 software.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530867&req=5

pone.0134054.g003: Correlation between clinical data and genetic diversity parameters with heterologous NAb response.Association between viral load (panel A), Cd4+T cells (panel B), years after infection (panel C), Shannon Entropy (panel D), p-distance (panel E), number of synonymous mutations (ds) (panel F), number of non-synonymous mutations (dn) (panel G) and the ratio ds/dn (Panel H) and number of cross-reactive subtypes was calculated. Median of the different clinical data and the genetic parameters for each patient (y axis) was plotted against the number of subtypes neutralized by each the patients (x axis). Patients are identified by the following symbols. LTNP 17 (blue triangle), LTNP 2 (purple triangle), LTNP 20 (green triangle), LTNP 21 (grey triangle), LTNP 3 (orange triangle), MDM (green circle), LTNP-5 (yellow circle), and LTNP 15 (red circle). Correlation between parameters was calculated by linear regression with a 95% of confidence using GraphPad Prism V 4.0 software. For the comparison of the values, a statistical analysis was performed with the non-parametric 2-tailed Mann-Whitney U test with a restrictive significance at the 95% using GraphPad Prism V 4.0 software.
Mentions: Viral load values and CD4+ T cell counts were recorded during the patient clinical follow-up and as shown in Fig 3A and 3B, there was no association between these clinical data nor between years after first HIV+ detection (Fig 3C) and the number of cross-reactive subtypes. In contrast, a positive correlation between viral diversity, measured as Shannon Entropy (p = 0.01, r2 = 0.66) (Fig 3D), or p-distance (p = 0.01, r2 = 0.51) (Fig 3E) and the number of cross-reactive subtypes was observed. This result suggested that viral diversity has contributed to the increase of Nab breadth in DI patients. This diversity was more contributed by the synonymous (Fig 3F) than to the non-synonymous changes (Fig 3G) but it was not significant in ds/dn ratios. In summary all these analysis supported a clear contribution of viral diversity, because of DI, to the neutralization breath in these patients.

Bottom Line: Our results showed an improved neutralization breadth in DI LTNP-EC patients when compared with matched LTNP single-infected patients.We found a positive correlation between neutralization breadth and diversity within the viral quasispecies.This correlation could explain why a group of LTNP-EC patients developed a broad neutralizing response despite having undetectable levels of viremia.

View Article: PubMed Central - PubMed

Affiliation: Centro Nacional de MicrobiologĂ­a (CNM), Instituto de Salud Carlos III, Majadahonda, Madrid 28220, Spain.

ABSTRACT
This study evaluated the neutralization breadth in dually infected (DI) HIV-1 long-term non-progressor elite controller patients (LTNP-EC) using a representative minipanel of 6 viruses from 5 different subtypes. Our results showed an improved neutralization breadth in DI LTNP-EC patients when compared with matched LTNP single-infected patients. The role of viral diversity in neutralization was estimated with the Shannon Entropy and the p-distance in viral quasispecies. We found a positive correlation between neutralization breadth and diversity within the viral quasispecies. This correlation could explain why a group of LTNP-EC patients developed a broad neutralizing response despite having undetectable levels of viremia.

No MeSH data available.


Related in: MedlinePlus