The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection.

The antiviral factor tripartite interaction motif 5alpha (Trim5alpha) restricts a broad range of retroviruses in a species-specific manner. Although human Trim5alpha is unable to block HIV-1 infection in human cells, a modest inhibition of HIV-1 replication has been reported. Recently two polymorphi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Daniëlle van Manen, Maarten A N Rits, Corrine Beugeling, Karel van Dort, Hanneke Schuitemaker, Neeltje A Kootstra
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7b1a1eb83b8b45e39f23fa13e36a2a56
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7b1a1eb83b8b45e39f23fa13e36a2a56
record_format	dspace
spelling	oai:doaj.org-article:7b1a1eb83b8b45e39f23fa13e36a2a562021-11-25T05:46:45ZThe effect of Trim5 polymorphisms on the clinical course of HIV-1 infection.1553-73661553-737410.1371/journal.ppat.0040018https://doaj.org/article/7b1a1eb83b8b45e39f23fa13e36a2a562008-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18248091/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The antiviral factor tripartite interaction motif 5alpha (Trim5alpha) restricts a broad range of retroviruses in a species-specific manner. Although human Trim5alpha is unable to block HIV-1 infection in human cells, a modest inhibition of HIV-1 replication has been reported. Recently two polymorphisms in the Trim5 gene (H43Y and R136Q) were shown to affect the antiviral activity of Trim5alpha in vitro. In this study, participants of the Amsterdam Cohort studies were screened for polymorphisms at amino acid residue 43 and 136 of the Trim5 gene, and the potential effects of these polymorphisms on the clinical course of HIV-1 infection were analyzed. In agreement with the reported decreased antiviral activity of Trim5alpha that contains a Y at amino acid residue 43 in vitro, an accelerated disease progression was observed for individuals who were homozygous for the 43Y genotype as compared to individuals who were heterozygous or homozygous for the 43H genotype. A protective effect of the 136Q genotype was observed but only after the emergence of CXCR4-using (X4) HIV-1 variants and when a viral load of 10(4.5) copies per ml plasma was used as an endpoint in survival analysis. Interestingly, naive CD4 T cells, which are selectively targeted by X4 HIV-1, revealed a significantly higher expression of Trim5alpha than memory CD4 T cells. In addition, we observed that the 136Q allele in combination with the -2GG genotype in the 5'UTR was associated with an accelerated disease progression. Thus, polymorphisms in the Trim5 gene may influence the clinical course of HIV-1 infection also underscoring the antiviral effect of Trim5alpha on HIV-1 in vivo.Daniëlle van ManenMaarten A N RitsCorrine BeugelingKarel van DortHanneke SchuitemakerNeeltje A KootstraPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 2, p e18 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Daniëlle van Manen Maarten A N Rits Corrine Beugeling Karel van Dort Hanneke Schuitemaker Neeltje A Kootstra The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection.
description	The antiviral factor tripartite interaction motif 5alpha (Trim5alpha) restricts a broad range of retroviruses in a species-specific manner. Although human Trim5alpha is unable to block HIV-1 infection in human cells, a modest inhibition of HIV-1 replication has been reported. Recently two polymorphisms in the Trim5 gene (H43Y and R136Q) were shown to affect the antiviral activity of Trim5alpha in vitro. In this study, participants of the Amsterdam Cohort studies were screened for polymorphisms at amino acid residue 43 and 136 of the Trim5 gene, and the potential effects of these polymorphisms on the clinical course of HIV-1 infection were analyzed. In agreement with the reported decreased antiviral activity of Trim5alpha that contains a Y at amino acid residue 43 in vitro, an accelerated disease progression was observed for individuals who were homozygous for the 43Y genotype as compared to individuals who were heterozygous or homozygous for the 43H genotype. A protective effect of the 136Q genotype was observed but only after the emergence of CXCR4-using (X4) HIV-1 variants and when a viral load of 10(4.5) copies per ml plasma was used as an endpoint in survival analysis. Interestingly, naive CD4 T cells, which are selectively targeted by X4 HIV-1, revealed a significantly higher expression of Trim5alpha than memory CD4 T cells. In addition, we observed that the 136Q allele in combination with the -2GG genotype in the 5'UTR was associated with an accelerated disease progression. Thus, polymorphisms in the Trim5 gene may influence the clinical course of HIV-1 infection also underscoring the antiviral effect of Trim5alpha on HIV-1 in vivo.
format	article
author	Daniëlle van Manen Maarten A N Rits Corrine Beugeling Karel van Dort Hanneke Schuitemaker Neeltje A Kootstra
author_facet	Daniëlle van Manen Maarten A N Rits Corrine Beugeling Karel van Dort Hanneke Schuitemaker Neeltje A Kootstra
author_sort	Daniëlle van Manen
title	The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection.
title_short	The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection.
title_full	The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection.
title_fullStr	The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection.
title_full_unstemmed	The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection.
title_sort	effect of trim5 polymorphisms on the clinical course of hiv-1 infection.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/7b1a1eb83b8b45e39f23fa13e36a2a56
work_keys_str_mv	AT daniellevanmanen theeffectoftrim5polymorphismsontheclinicalcourseofhiv1infection AT maartenanrits theeffectoftrim5polymorphismsontheclinicalcourseofhiv1infection AT corrinebeugeling theeffectoftrim5polymorphismsontheclinicalcourseofhiv1infection AT karelvandort theeffectoftrim5polymorphismsontheclinicalcourseofhiv1infection AT hannekeschuitemaker theeffectoftrim5polymorphismsontheclinicalcourseofhiv1infection AT neeltjeakootstra theeffectoftrim5polymorphismsontheclinicalcourseofhiv1infection AT daniellevanmanen effectoftrim5polymorphismsontheclinicalcourseofhiv1infection AT maartenanrits effectoftrim5polymorphismsontheclinicalcourseofhiv1infection AT corrinebeugeling effectoftrim5polymorphismsontheclinicalcourseofhiv1infection AT karelvandort effectoftrim5polymorphismsontheclinicalcourseofhiv1infection AT hannekeschuitemaker effectoftrim5polymorphismsontheclinicalcourseofhiv1infection AT neeltjeakootstra effectoftrim5polymorphismsontheclinicalcourseofhiv1infection
_version_	1718414464415432704

The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection.

Ejemplares similares