HIV-1 disease progression is associated with bile-salt stimulated lipase (BSSL) gene polymorphism.

<h4>Background</h4>DC-SIGN expressed by dendritic cells captures HIV-1 resulting in trans-infection of CD4(+) T-lymphocytes. However, BSSL (bile-salt stimulated lipase) binding to DC-SIGN interferes with HIV-1 capture. DC-SIGN binding properties of BSSL associate with the polymorphic rep...

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Autores principales:	Martijn J Stax, Neeltje A Kootstra, Angélique B van 't Wout, Michael W T Tanck, Margreet Bakker, Georgios Pollakis, William A Paxton
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e420b8d6bfe94ac2bf25aa55f32116cc
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spelling	oai:doaj.org-article:e420b8d6bfe94ac2bf25aa55f32116cc2021-11-18T07:25:58ZHIV-1 disease progression is associated with bile-salt stimulated lipase (BSSL) gene polymorphism.1932-620310.1371/journal.pone.0032534https://doaj.org/article/e420b8d6bfe94ac2bf25aa55f32116cc2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22412885/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>DC-SIGN expressed by dendritic cells captures HIV-1 resulting in trans-infection of CD4(+) T-lymphocytes. However, BSSL (bile-salt stimulated lipase) binding to DC-SIGN interferes with HIV-1 capture. DC-SIGN binding properties of BSSL associate with the polymorphic repeated motif of BSSL exon 11. Furthermore, BSSL binds to HIV-1 co-receptor CXCR4. We hypothesized that BSSL modulates HIV-1 disease progression and emergence of CXCR4 using HIV-1 (X4) variants.<h4>Results</h4>The relation between BSSL genotype and HIV-1 disease progression and emergence of X4 variants was studied using Kaplan Meier and multivariate Cox proportional hazard analysis in a cohort of HIV-1 infected men having sex with men (n = 334, with n = 130 seroconverters). We analyzed the association of BSSL genotype with set-point viral load and CD4 cell count, both pre-infection and post-infection at viral set-point. The number of repeats in BSSL exon 11 were highly variable ranging from 10 to 18 in seropositive individuals and from 5-17 in HRSN with 16 repeats being dominant (>80% carry at least one allele with 16 repeats). We defined 16 to 18 repeats as high (H) and less than 16 repeats as low (L) repeat numbers. Homozygosity for the high (H) repeat number BSSL genotype (HH) correlated with high CD4 cell numbers prior to infection (p = 0.007). In HIV-1 patients, delayed disease progression was linked to the HH BSSL genotype (RH = 0.462 CI = 0.282-0.757, p = 0.002) as was delayed emergence of X4 variants (RH = 0.525, 95% CI = 0.290-0.953, p = 0.034). The LH BSSL genotype, previously found to be associated with enhanced DC-SIGN binding of human milk, was identified to correlate with accelerated disease progression in our cohort of HIV-1 infected MSM (RH = 0.517, 95% CI = 0.328-0.818, p = 0.005).<h4>Conclusion</h4>We identify BSSL as a marker for HIV-1 disease progression and emergence of X4 variants. Additionally, we identified a relation between BSSL genotype and CD4 cell counts prior to infection.Martijn J StaxNeeltje A KootstraAngélique B van 't WoutMichael W T TanckMargreet BakkerGeorgios PollakisWilliam A PaxtonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e32534 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martijn J Stax Neeltje A Kootstra Angélique B van 't Wout Michael W T Tanck Margreet Bakker Georgios Pollakis William A Paxton HIV-1 disease progression is associated with bile-salt stimulated lipase (BSSL) gene polymorphism.
description	<h4>Background</h4>DC-SIGN expressed by dendritic cells captures HIV-1 resulting in trans-infection of CD4(+) T-lymphocytes. However, BSSL (bile-salt stimulated lipase) binding to DC-SIGN interferes with HIV-1 capture. DC-SIGN binding properties of BSSL associate with the polymorphic repeated motif of BSSL exon 11. Furthermore, BSSL binds to HIV-1 co-receptor CXCR4. We hypothesized that BSSL modulates HIV-1 disease progression and emergence of CXCR4 using HIV-1 (X4) variants.<h4>Results</h4>The relation between BSSL genotype and HIV-1 disease progression and emergence of X4 variants was studied using Kaplan Meier and multivariate Cox proportional hazard analysis in a cohort of HIV-1 infected men having sex with men (n = 334, with n = 130 seroconverters). We analyzed the association of BSSL genotype with set-point viral load and CD4 cell count, both pre-infection and post-infection at viral set-point. The number of repeats in BSSL exon 11 were highly variable ranging from 10 to 18 in seropositive individuals and from 5-17 in HRSN with 16 repeats being dominant (>80% carry at least one allele with 16 repeats). We defined 16 to 18 repeats as high (H) and less than 16 repeats as low (L) repeat numbers. Homozygosity for the high (H) repeat number BSSL genotype (HH) correlated with high CD4 cell numbers prior to infection (p = 0.007). In HIV-1 patients, delayed disease progression was linked to the HH BSSL genotype (RH = 0.462 CI = 0.282-0.757, p = 0.002) as was delayed emergence of X4 variants (RH = 0.525, 95% CI = 0.290-0.953, p = 0.034). The LH BSSL genotype, previously found to be associated with enhanced DC-SIGN binding of human milk, was identified to correlate with accelerated disease progression in our cohort of HIV-1 infected MSM (RH = 0.517, 95% CI = 0.328-0.818, p = 0.005).<h4>Conclusion</h4>We identify BSSL as a marker for HIV-1 disease progression and emergence of X4 variants. Additionally, we identified a relation between BSSL genotype and CD4 cell counts prior to infection.
format	article
author	Martijn J Stax Neeltje A Kootstra Angélique B van 't Wout Michael W T Tanck Margreet Bakker Georgios Pollakis William A Paxton
author_facet	Martijn J Stax Neeltje A Kootstra Angélique B van 't Wout Michael W T Tanck Margreet Bakker Georgios Pollakis William A Paxton
author_sort	Martijn J Stax
title	HIV-1 disease progression is associated with bile-salt stimulated lipase (BSSL) gene polymorphism.
title_short	HIV-1 disease progression is associated with bile-salt stimulated lipase (BSSL) gene polymorphism.
title_full	HIV-1 disease progression is associated with bile-salt stimulated lipase (BSSL) gene polymorphism.
title_fullStr	HIV-1 disease progression is associated with bile-salt stimulated lipase (BSSL) gene polymorphism.
title_full_unstemmed	HIV-1 disease progression is associated with bile-salt stimulated lipase (BSSL) gene polymorphism.
title_sort	hiv-1 disease progression is associated with bile-salt stimulated lipase (bssl) gene polymorphism.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/e420b8d6bfe94ac2bf25aa55f32116cc
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HIV-1 disease progression is associated with bile-salt stimulated lipase (BSSL) gene polymorphism.

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