Loading…

Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1: e1003496

SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2013-07, Vol.9 (7)
Main Authors: Fregoso, Oliver I, Ahn, Jinwoo, Wang, Chuanping, Mehrens, Jennifer, Skowronski, Jacek, Emerman, Michael
Format: Article
Language:English
Subjects:
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites
container_end_page
container_issue 7
container_start_page
container_title PLoS pathogens
container_volume 9
creator Fregoso, Oliver I
Ahn, Jinwoo
Wang, Chuanping
Mehrens, Jennifer
Skowronski, Jacek
Emerman, Michael
description SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts.
doi_str_mv 10.1371/journal.ppat.1003496
format article
fullrecord <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_journals_1430786406</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3066040121</sourcerecordid><originalsourceid>FETCH-proquest_journals_14307864063</originalsourceid><addsrcrecordid>eNqNj0FrAjEUhENRqFX_QQ-Bnl3zSMzWY6mKl16qeJUQsvFJSGKSlfrvu1ukZ08zDN8MDCGvwCrgNczPoU1euSpGVSpgjIulfCIjWCz4rOa1GPx7KZ_JS85nxgRwkCPi19fg2oLBq3Sj-2CtQ29paOgh_swPMdFdNBob1Fhu9Nvk1pVM0dMVXk2yxpcu1MF67Df6XjmZnisJ9V-0UbqEbubja7uCCRk2ymUzveuYvG3W-8_tLKZwabvW8f4lH0FwVr9LwSR_jPoFiNhTHQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1430786406</pqid></control><display><type>article</type><title>Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1: e1003496</title><source>PubMed Central(OpenAccess)</source><source>ProQuest Publicly Available Content database</source><creator>Fregoso, Oliver I ; Ahn, Jinwoo ; Wang, Chuanping ; Mehrens, Jennifer ; Skowronski, Jacek ; Emerman, Michael</creator><creatorcontrib>Fregoso, Oliver I ; Ahn, Jinwoo ; Wang, Chuanping ; Mehrens, Jennifer ; Skowronski, Jacek ; Emerman, Michael</creatorcontrib><description>SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts.</description><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1003496</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>HIV ; Human immunodeficiency virus ; Infections ; Microbiology ; Molecular weight ; Proteins ; Viruses</subject><ispartof>PLoS pathogens, 2013-07, Vol.9 (7)</ispartof><rights>2013 Fregoso et al. 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 credited: Fregoso OI, Ahn J, Wang C, Mehrens J, Skowronski J, et al. (2013) Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1. PLoS Pathog 9(7): e1003496. doi:10.1371/journal.ppat.1003496</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1430786406/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1430786406?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,25753,27924,27925,37012,44590,75126</link.rule.ids></links><search><creatorcontrib>Fregoso, Oliver I</creatorcontrib><creatorcontrib>Ahn, Jinwoo</creatorcontrib><creatorcontrib>Wang, Chuanping</creatorcontrib><creatorcontrib>Mehrens, Jennifer</creatorcontrib><creatorcontrib>Skowronski, Jacek</creatorcontrib><creatorcontrib>Emerman, Michael</creatorcontrib><title>Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1: e1003496</title><title>PLoS pathogens</title><description>SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts.</description><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Infections</subject><subject>Microbiology</subject><subject>Molecular weight</subject><subject>Proteins</subject><subject>Viruses</subject><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNqNj0FrAjEUhENRqFX_QQ-Bnl3zSMzWY6mKl16qeJUQsvFJSGKSlfrvu1ukZ08zDN8MDCGvwCrgNczPoU1euSpGVSpgjIulfCIjWCz4rOa1GPx7KZ_JS85nxgRwkCPi19fg2oLBq3Sj-2CtQ29paOgh_swPMdFdNBob1Fhu9Nvk1pVM0dMVXk2yxpcu1MF67Df6XjmZnisJ9V-0UbqEbubja7uCCRk2ymUzveuYvG3W-8_tLKZwabvW8f4lH0FwVr9LwSR_jPoFiNhTHQ</recordid><startdate>20130701</startdate><enddate>20130701</enddate><creator>Fregoso, Oliver I</creator><creator>Ahn, Jinwoo</creator><creator>Wang, Chuanping</creator><creator>Mehrens, Jennifer</creator><creator>Skowronski, Jacek</creator><creator>Emerman, Michael</creator><general>Public Library of Science</general><scope>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20130701</creationdate><title>Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1</title><author>Fregoso, Oliver I ; Ahn, Jinwoo ; Wang, Chuanping ; Mehrens, Jennifer ; Skowronski, Jacek ; Emerman, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_journals_14307864063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>HIV</topic><topic>Human immunodeficiency virus</topic><topic>Infections</topic><topic>Microbiology</topic><topic>Molecular weight</topic><topic>Proteins</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fregoso, Oliver I</creatorcontrib><creatorcontrib>Ahn, Jinwoo</creatorcontrib><creatorcontrib>Wang, Chuanping</creatorcontrib><creatorcontrib>Mehrens, Jennifer</creatorcontrib><creatorcontrib>Skowronski, Jacek</creatorcontrib><creatorcontrib>Emerman, Michael</creatorcontrib><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Biological Science Journals</collection><collection>ProQuest Publicly Available Content database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fregoso, Oliver I</au><au>Ahn, Jinwoo</au><au>Wang, Chuanping</au><au>Mehrens, Jennifer</au><au>Skowronski, Jacek</au><au>Emerman, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1: e1003496</atitle><jtitle>PLoS pathogens</jtitle><date>2013-07-01</date><risdate>2013</risdate><volume>9</volume><issue>7</issue><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><doi>10.1371/journal.ppat.1003496</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1553-7366
ispartof PLoS pathogens, 2013-07, Vol.9 (7)
issn 1553-7366
1553-7374
language eng
recordid cdi_proquest_journals_1430786406
source PubMed Central(OpenAccess); ProQuest Publicly Available Content database
subjects HIV
Human immunodeficiency virus
Infections
Microbiology
Molecular weight
Proteins
Viruses
title Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1: e1003496
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T18%3A54%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evolutionary%20Toggling%20of%20Vpx/Vpr%20Specificity%20Results%20in%20Divergent%20Recognition%20of%20the%20Restriction%20Factor%20SAMHD1:%20e1003496&rft.jtitle=PLoS%20pathogens&rft.au=Fregoso,%20Oliver%20I&rft.date=2013-07-01&rft.volume=9&rft.issue=7&rft.issn=1553-7366&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1003496&rft_dat=%3Cproquest%3E3066040121%3C/proquest%3E%3Cgrp_id%3Ecdi_FETCH-proquest_journals_14307864063%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1430786406&rft_id=info:pmid/&rfr_iscdi=true