Cargando…
Coreceptor and Cytokine Concentrations May Not Explain Differences in Disease Progression Observed in HIV-1 Clade A and D Infected Ugandans
BACKGROUND: The use of cellular coreceptors and modulation of cytokine concentrations by HIV to establish a productive infection is well documented. However, it is unknown whether the expression of these proteins affects the course of HIV clade A and D disease, reported to have different progression...
Autores principales: | , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104992/ https://www.ncbi.nlm.nih.gov/pubmed/21655330 http://dx.doi.org/10.1371/journal.pone.0019902 |
_version_ | 1782204663181869056 |
---|---|
author | Wright, Edward Mugaba, Susan Grant, Paul Parkes-Ratanshi, Rosalind Van der Paal, Lieve Grosskurth, Heiner Kaleebu, Pontiano |
author_facet | Wright, Edward Mugaba, Susan Grant, Paul Parkes-Ratanshi, Rosalind Van der Paal, Lieve Grosskurth, Heiner Kaleebu, Pontiano |
author_sort | Wright, Edward |
collection | PubMed |
description | BACKGROUND: The use of cellular coreceptors and modulation of cytokine concentrations by HIV to establish a productive infection is well documented. However, it is unknown whether the expression of these proteins affects the course of HIV clade A and D disease, reported to have different progression rates. METHODOLOGY/PRINCIPAL FINDINGS: We investigated whether the number of CD4(+) T-cells expressing CCR5 or CXCR4, the density of these coreceptors and concentrations of specific immune proteins linked to HIV pathogenesis vary between individuals infected with HIV clade A or D. We undertook additional analyses stratifying participants by early (CD4>500 cells/µl) or late (CD4<200 cells/µl) disease stage. Whole blood samples were taken from 50 HIV-1 infected individuals drawn from cohorts in rural south-west Uganda. Late stage participants had less than half the number of CD4(+)/CCR5(+) T-cells (p = 0.0113) and 5.6 times fewer CD4(+)/CXCR4(+) cells (p<0.0001) than early stage participants. There was also a statistically significant difference in the density of CXCR4 on CD4(+) cells between clade A and D infected early stage participants (142 [A] vs 84 [D]; p = 0.0146). Across all participants we observed significantly higher concentration of Th(1) cytokines compared to Th(2) (66.4 vs 23.8 pg/ml; p<0.0001). Plasma concentrations of IFNγ and IL-2 were 1.8 and 2.4 fold lower respectively in Late-D infected participants compared to Late-A participants. MIP-1β levels also decreased from 118.0 pg/ml to 47.1 pg/ml (p = 0.0396) as HIV disease progressed. CONCLUSIONS/SIGNIFICANCE: We observed specific alterations in the abundance of CD4(+)/CCR5(+) and CD4(+)/CXCR4(+) T-cells, and concentrations of immune proteins across different HIV clades and as infection progresses. Our results suggest that these changes are unlikely to explain the observed differences in disease progression between subtype A and D infections. However, our observations further the understanding of the natural progression of non-clade B HIV infection and how the virus adapts to exploit the host environment. |
format | Text |
id | pubmed-3104992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31049922011-06-08 Coreceptor and Cytokine Concentrations May Not Explain Differences in Disease Progression Observed in HIV-1 Clade A and D Infected Ugandans Wright, Edward Mugaba, Susan Grant, Paul Parkes-Ratanshi, Rosalind Van der Paal, Lieve Grosskurth, Heiner Kaleebu, Pontiano PLoS One Research Article BACKGROUND: The use of cellular coreceptors and modulation of cytokine concentrations by HIV to establish a productive infection is well documented. However, it is unknown whether the expression of these proteins affects the course of HIV clade A and D disease, reported to have different progression rates. METHODOLOGY/PRINCIPAL FINDINGS: We investigated whether the number of CD4(+) T-cells expressing CCR5 or CXCR4, the density of these coreceptors and concentrations of specific immune proteins linked to HIV pathogenesis vary between individuals infected with HIV clade A or D. We undertook additional analyses stratifying participants by early (CD4>500 cells/µl) or late (CD4<200 cells/µl) disease stage. Whole blood samples were taken from 50 HIV-1 infected individuals drawn from cohorts in rural south-west Uganda. Late stage participants had less than half the number of CD4(+)/CCR5(+) T-cells (p = 0.0113) and 5.6 times fewer CD4(+)/CXCR4(+) cells (p<0.0001) than early stage participants. There was also a statistically significant difference in the density of CXCR4 on CD4(+) cells between clade A and D infected early stage participants (142 [A] vs 84 [D]; p = 0.0146). Across all participants we observed significantly higher concentration of Th(1) cytokines compared to Th(2) (66.4 vs 23.8 pg/ml; p<0.0001). Plasma concentrations of IFNγ and IL-2 were 1.8 and 2.4 fold lower respectively in Late-D infected participants compared to Late-A participants. MIP-1β levels also decreased from 118.0 pg/ml to 47.1 pg/ml (p = 0.0396) as HIV disease progressed. CONCLUSIONS/SIGNIFICANCE: We observed specific alterations in the abundance of CD4(+)/CCR5(+) and CD4(+)/CXCR4(+) T-cells, and concentrations of immune proteins across different HIV clades and as infection progresses. Our results suggest that these changes are unlikely to explain the observed differences in disease progression between subtype A and D infections. However, our observations further the understanding of the natural progression of non-clade B HIV infection and how the virus adapts to exploit the host environment. Public Library of Science 2011-05-31 /pmc/articles/PMC3104992/ /pubmed/21655330 http://dx.doi.org/10.1371/journal.pone.0019902 Text en Wright 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 Wright, Edward Mugaba, Susan Grant, Paul Parkes-Ratanshi, Rosalind Van der Paal, Lieve Grosskurth, Heiner Kaleebu, Pontiano Coreceptor and Cytokine Concentrations May Not Explain Differences in Disease Progression Observed in HIV-1 Clade A and D Infected Ugandans |
title | Coreceptor and Cytokine Concentrations May Not Explain Differences in Disease Progression Observed in HIV-1 Clade A and D Infected Ugandans |
title_full | Coreceptor and Cytokine Concentrations May Not Explain Differences in Disease Progression Observed in HIV-1 Clade A and D Infected Ugandans |
title_fullStr | Coreceptor and Cytokine Concentrations May Not Explain Differences in Disease Progression Observed in HIV-1 Clade A and D Infected Ugandans |
title_full_unstemmed | Coreceptor and Cytokine Concentrations May Not Explain Differences in Disease Progression Observed in HIV-1 Clade A and D Infected Ugandans |
title_short | Coreceptor and Cytokine Concentrations May Not Explain Differences in Disease Progression Observed in HIV-1 Clade A and D Infected Ugandans |
title_sort | coreceptor and cytokine concentrations may not explain differences in disease progression observed in hiv-1 clade a and d infected ugandans |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104992/ https://www.ncbi.nlm.nih.gov/pubmed/21655330 http://dx.doi.org/10.1371/journal.pone.0019902 |
work_keys_str_mv | AT wrightedward coreceptorandcytokineconcentrationsmaynotexplaindifferencesindiseaseprogressionobservedinhiv1cladeaanddinfectedugandans AT mugabasusan coreceptorandcytokineconcentrationsmaynotexplaindifferencesindiseaseprogressionobservedinhiv1cladeaanddinfectedugandans AT grantpaul coreceptorandcytokineconcentrationsmaynotexplaindifferencesindiseaseprogressionobservedinhiv1cladeaanddinfectedugandans AT parkesratanshirosalind coreceptorandcytokineconcentrationsmaynotexplaindifferencesindiseaseprogressionobservedinhiv1cladeaanddinfectedugandans AT vanderpaallieve coreceptorandcytokineconcentrationsmaynotexplaindifferencesindiseaseprogressionobservedinhiv1cladeaanddinfectedugandans AT grosskurthheiner coreceptorandcytokineconcentrationsmaynotexplaindifferencesindiseaseprogressionobservedinhiv1cladeaanddinfectedugandans AT kaleebupontiano coreceptorandcytokineconcentrationsmaynotexplaindifferencesindiseaseprogressionobservedinhiv1cladeaanddinfectedugandans |