HIV-1 nef protein structures associated with brain infection and dementia pathogenesis.

The difference between regional rates of HIV-associated dementia (HAD) in patients infected with different subtypes of HIV suggests that genetic determinants exist within HIV that influence the ability of the virus to replicate in the central nervous system (in Uganda, Africa, subtype D HAD rate is...

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Autores principales:	Susanna L Lamers, Art F Y Poon, Michael S McGrath
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b887c44bc399434191534a02c2b6ec68
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spelling	oai:doaj.org-article:b887c44bc399434191534a02c2b6ec682021-11-18T06:59:00ZHIV-1 nef protein structures associated with brain infection and dementia pathogenesis.1932-620310.1371/journal.pone.0016659https://doaj.org/article/b887c44bc399434191534a02c2b6ec682011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347424/?tool=EBIhttps://doaj.org/toc/1932-6203The difference between regional rates of HIV-associated dementia (HAD) in patients infected with different subtypes of HIV suggests that genetic determinants exist within HIV that influence the ability of the virus to replicate in the central nervous system (in Uganda, Africa, subtype D HAD rate is 89%, while subtype A HAD rate is 24%). HIV-1 nef is a multifunctional protein with known toxic effects in the brain compartment. The goal of the current study was to identify if specific three-dimensional nef structures may be linked to patients who developed HAD. HIV-1 nef structures were computationally derived for consensus brain and non-brain sequences from a panel of patients infected with subtype B who died due to varied disease pathologies and consensus subtype A and subtype D sequences from Uganda. Site directed mutation analysis identified signatures in brain structures that appear to change binding potentials and could affect folding conformations of brain-associated structures. Despite the large sequence variation between HIV subtypes, structural alignments confirmed that viral structures derived from patients with HAD were more similar to subtype D structures than to structures derived from patient sequences without HAD. Furthermore, structures derived from brain sequences of patients with HAD were more similar to subtype D structures than they were to their own non-brain structures. The potential finding of a brain-specific nef structure indicates that HAD may result from genetic alterations that alter the folding or binding potential of the protein.Susanna L LamersArt F Y PoonMichael S McGrathPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e16659 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Susanna L Lamers Art F Y Poon Michael S McGrath HIV-1 nef protein structures associated with brain infection and dementia pathogenesis.
description	The difference between regional rates of HIV-associated dementia (HAD) in patients infected with different subtypes of HIV suggests that genetic determinants exist within HIV that influence the ability of the virus to replicate in the central nervous system (in Uganda, Africa, subtype D HAD rate is 89%, while subtype A HAD rate is 24%). HIV-1 nef is a multifunctional protein with known toxic effects in the brain compartment. The goal of the current study was to identify if specific three-dimensional nef structures may be linked to patients who developed HAD. HIV-1 nef structures were computationally derived for consensus brain and non-brain sequences from a panel of patients infected with subtype B who died due to varied disease pathologies and consensus subtype A and subtype D sequences from Uganda. Site directed mutation analysis identified signatures in brain structures that appear to change binding potentials and could affect folding conformations of brain-associated structures. Despite the large sequence variation between HIV subtypes, structural alignments confirmed that viral structures derived from patients with HAD were more similar to subtype D structures than to structures derived from patient sequences without HAD. Furthermore, structures derived from brain sequences of patients with HAD were more similar to subtype D structures than they were to their own non-brain structures. The potential finding of a brain-specific nef structure indicates that HAD may result from genetic alterations that alter the folding or binding potential of the protein.
format	article
author	Susanna L Lamers Art F Y Poon Michael S McGrath
author_facet	Susanna L Lamers Art F Y Poon Michael S McGrath
author_sort	Susanna L Lamers
title	HIV-1 nef protein structures associated with brain infection and dementia pathogenesis.
title_short	HIV-1 nef protein structures associated with brain infection and dementia pathogenesis.
title_full	HIV-1 nef protein structures associated with brain infection and dementia pathogenesis.
title_fullStr	HIV-1 nef protein structures associated with brain infection and dementia pathogenesis.
title_full_unstemmed	HIV-1 nef protein structures associated with brain infection and dementia pathogenesis.
title_sort	hiv-1 nef protein structures associated with brain infection and dementia pathogenesis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/b887c44bc399434191534a02c2b6ec68
work_keys_str_mv	AT susannallamers hiv1nefproteinstructuresassociatedwithbraininfectionanddementiapathogenesis AT artfypoon hiv1nefproteinstructuresassociatedwithbraininfectionanddementiapathogenesis AT michaelsmcgrath hiv1nefproteinstructuresassociatedwithbraininfectionanddementiapathogenesis
_version_	1718424128817463296

HIV-1 nef protein structures associated with brain infection and dementia pathogenesis.

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