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Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities

APOBEC3H (A3H) is a member of the APOBEC3 family of proteins with varying activities against retroviruses and retrotransposons. The A3H gene contains several single nucleotide polymorphisms and up to seven haplotypes have been detected in humans. Although variations in anti-viral function among A3H...

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Autores principales: Zhen, Anjie, Du, Juan, Zhou, Xiaohong, Xiong, Yong, Yu, Xiao-Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408456/
https://www.ncbi.nlm.nih.gov/pubmed/22859935
http://dx.doi.org/10.1371/journal.pone.0038771
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author Zhen, Anjie
Du, Juan
Zhou, Xiaohong
Xiong, Yong
Yu, Xiao-Fang
author_facet Zhen, Anjie
Du, Juan
Zhou, Xiaohong
Xiong, Yong
Yu, Xiao-Fang
author_sort Zhen, Anjie
collection PubMed
description APOBEC3H (A3H) is a member of the APOBEC3 family of proteins with varying activities against retroviruses and retrotransposons. The A3H gene contains several single nucleotide polymorphisms and up to seven haplotypes have been detected in humans. Although variations in anti-viral function among A3H haplotypes are not fully understood, only 15N105R-containing A3H variants are known to have potent activities against Vif-deficient HIV-1. Unique motif RLYY(F/Y)W of APOBEC3G (A3G) and APOBEC3F (A3F) required for 7SL RNA binding and HIV-1 incorporation is also conserved in all A3H variants. Like A3G, A3H HapII also demonstrated high binding affinity to host small RNAs such as 7SL and Y RNAs. Mutation of a critical amino acid, W115A resulted in reduced expression level, decreased affinity for 7SL RNA, impairment of virion packaging and reduced anti-viral activity. By comparison, A3H HapI had lower binding affinities to host small RNAs and reduced efficiency of virion incorporation, resulting in significantly reduced anti-viral activity. The SNP ΔN15 commonly found in A3H HapIII and HapIV abolished their abilities to associate with RNAs, and A3H HapIIΔ15N failed to package into HIV-1 virions or exhibited any anti-viral activity. Finally, we showed that A3H variants had distinct cellular localization patterns, which correlated with their different RNA binding affinities. Thus, Pol-III RNA such as 7SL RNA binding is a conserved feature of potent anti-HIV human APOBEC3 cytidine deaminases.
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spelling pubmed-34084562012-08-02 Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities Zhen, Anjie Du, Juan Zhou, Xiaohong Xiong, Yong Yu, Xiao-Fang PLoS One Research Article APOBEC3H (A3H) is a member of the APOBEC3 family of proteins with varying activities against retroviruses and retrotransposons. The A3H gene contains several single nucleotide polymorphisms and up to seven haplotypes have been detected in humans. Although variations in anti-viral function among A3H haplotypes are not fully understood, only 15N105R-containing A3H variants are known to have potent activities against Vif-deficient HIV-1. Unique motif RLYY(F/Y)W of APOBEC3G (A3G) and APOBEC3F (A3F) required for 7SL RNA binding and HIV-1 incorporation is also conserved in all A3H variants. Like A3G, A3H HapII also demonstrated high binding affinity to host small RNAs such as 7SL and Y RNAs. Mutation of a critical amino acid, W115A resulted in reduced expression level, decreased affinity for 7SL RNA, impairment of virion packaging and reduced anti-viral activity. By comparison, A3H HapI had lower binding affinities to host small RNAs and reduced efficiency of virion incorporation, resulting in significantly reduced anti-viral activity. The SNP ΔN15 commonly found in A3H HapIII and HapIV abolished their abilities to associate with RNAs, and A3H HapIIΔ15N failed to package into HIV-1 virions or exhibited any anti-viral activity. Finally, we showed that A3H variants had distinct cellular localization patterns, which correlated with their different RNA binding affinities. Thus, Pol-III RNA such as 7SL RNA binding is a conserved feature of potent anti-HIV human APOBEC3 cytidine deaminases. Public Library of Science 2012-07-30 /pmc/articles/PMC3408456/ /pubmed/22859935 http://dx.doi.org/10.1371/journal.pone.0038771 Text en © 2012 Zhen 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
Zhen, Anjie
Du, Juan
Zhou, Xiaohong
Xiong, Yong
Yu, Xiao-Fang
Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities
title Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities
title_full Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities
title_fullStr Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities
title_full_unstemmed Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities
title_short Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities
title_sort reduced apobec3h variant anti-viral activities are associated with altered rna binding activities
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408456/
https://www.ncbi.nlm.nih.gov/pubmed/22859935
http://dx.doi.org/10.1371/journal.pone.0038771
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