Delineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition.

Human α-defensins are potent anti-microbial peptides with the ability to neutralize bacterial and viral targets. Single alanine mutagenesis has been used to identify determinants of anti-bacterial activity and binding to bacterial proteins such as anthrax lethal factor. Similar analyses of α-defensi...

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Autores principales:	Victoria R Tenge, Anshu P Gounder, Mayim E Wiens, Wuyuan Lu, Jason G Smith
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ad892edd516044cd9b0a3422a861febb
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spelling	oai:doaj.org-article:ad892edd516044cd9b0a3422a861febb2021-11-25T05:46:05ZDelineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition.1553-73661553-737410.1371/journal.ppat.1004360https://doaj.org/article/ad892edd516044cd9b0a3422a861febb2014-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25188351/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Human α-defensins are potent anti-microbial peptides with the ability to neutralize bacterial and viral targets. Single alanine mutagenesis has been used to identify determinants of anti-bacterial activity and binding to bacterial proteins such as anthrax lethal factor. Similar analyses of α-defensin interactions with non-enveloped viruses are limited. We used a comprehensive set of human α-defensin 5 (HD5) and human neutrophil peptide 1 (HNP1) alanine scan mutants in a combination of binding and neutralization assays with human adenovirus (AdV) and human papillomavirus (HPV). We have identified a core of critical hydrophobic residues that are common determinants for all of the virus-defensin interactions that were analyzed, while specificity in viral recognition is conferred by specific surface-exposed charged residues. The hydrophobic residues serve multiple roles in maintaining the tertiary and quaternary structure of the defensins as well as forming an interface for virus binding. Many of the important solvent-exposed residues of HD5 group together to form a critical surface. However, a single discrete binding face was not identified for HNP1. In lieu of whole AdV, we used a recombinant capsid subunit comprised of penton base and fiber in quantitative binding studies and determined that the anti-viral potency of HD5 was a function of stoichiometry rather than affinity. Our studies support a mechanism in which α-defensins depend on hydrophobic and charge-charge interactions to bind at high copy number to these non-enveloped viruses to neutralize infection and provide insight into properties that guide α-defensin anti-viral activity.Victoria R TengeAnshu P GounderMayim E WiensWuyuan LuJason G SmithPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 9, p e1004360 (2014)
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 Victoria R Tenge Anshu P Gounder Mayim E Wiens Wuyuan Lu Jason G Smith Delineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition.
description	Human α-defensins are potent anti-microbial peptides with the ability to neutralize bacterial and viral targets. Single alanine mutagenesis has been used to identify determinants of anti-bacterial activity and binding to bacterial proteins such as anthrax lethal factor. Similar analyses of α-defensin interactions with non-enveloped viruses are limited. We used a comprehensive set of human α-defensin 5 (HD5) and human neutrophil peptide 1 (HNP1) alanine scan mutants in a combination of binding and neutralization assays with human adenovirus (AdV) and human papillomavirus (HPV). We have identified a core of critical hydrophobic residues that are common determinants for all of the virus-defensin interactions that were analyzed, while specificity in viral recognition is conferred by specific surface-exposed charged residues. The hydrophobic residues serve multiple roles in maintaining the tertiary and quaternary structure of the defensins as well as forming an interface for virus binding. Many of the important solvent-exposed residues of HD5 group together to form a critical surface. However, a single discrete binding face was not identified for HNP1. In lieu of whole AdV, we used a recombinant capsid subunit comprised of penton base and fiber in quantitative binding studies and determined that the anti-viral potency of HD5 was a function of stoichiometry rather than affinity. Our studies support a mechanism in which α-defensins depend on hydrophobic and charge-charge interactions to bind at high copy number to these non-enveloped viruses to neutralize infection and provide insight into properties that guide α-defensin anti-viral activity.
format	article
author	Victoria R Tenge Anshu P Gounder Mayim E Wiens Wuyuan Lu Jason G Smith
author_facet	Victoria R Tenge Anshu P Gounder Mayim E Wiens Wuyuan Lu Jason G Smith
author_sort	Victoria R Tenge
title	Delineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition.
title_short	Delineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition.
title_full	Delineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition.
title_fullStr	Delineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition.
title_full_unstemmed	Delineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition.
title_sort	delineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ad892edd516044cd9b0a3422a861febb
work_keys_str_mv	AT victoriartenge delineationofinterfacesonhumanalphadefensinscriticalforhumanadenovirusandhumanpapillomavirusinhibition AT anshupgounder delineationofinterfacesonhumanalphadefensinscriticalforhumanadenovirusandhumanpapillomavirusinhibition AT mayimewiens delineationofinterfacesonhumanalphadefensinscriticalforhumanadenovirusandhumanpapillomavirusinhibition AT wuyuanlu delineationofinterfacesonhumanalphadefensinscriticalforhumanadenovirusandhumanpapillomavirusinhibition AT jasongsmith delineationofinterfacesonhumanalphadefensinscriticalforhumanadenovirusandhumanpapillomavirusinhibition
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Delineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition.

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