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Article: A simian immunodeficiency virus V3 loop mutant that does not efficiently use CCR5 or common alternative coreceptors is moderately attenuated in vivo

TitleA simian immunodeficiency virus V3 loop mutant that does not efficiently use CCR5 or common alternative coreceptors is moderately attenuated in vivo
Authors
KeywordsCCR5
Coreceptor
Pathogenesis
SIV
TAK-779
Issue Date2007
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yviro
Citation
Virology, 2007, v. 360 n. 2, p. 275-285 How to Cite?
AbstractSexually transmitted HIV-1 strains utilize the chemokine receptor CCR5 for viral entry and inhibitors targeting this coreceptor offer great promise for antiretroviral therapy. They also raise the question, however, whether viral variants exhibiting altered coreceptor interactions and resistance against these antiviral agents might still be pathogenic. In the present study, we analyzed a SIVmac239 envelope (Env) mutant (239DL) containing two mutations in the V3 loop which reduced viral entry via CCR5 by 10- to 20-fold, disrupted utilization of common alternative SIV coreceptors and changed the way Env engaged CCR5. To evaluate its replicative capacity and pathogenic potential in vivo we infected six rhesus macaques with 239DL. We found that 239DL replication was only slightly attenuated early during infection. Thereafter, a D324V change, which restored efficient CCR5 usage and coincided with 239wt-like levels of viral replication, emerged in two animals. In contrast, the viral geno- and phenotype remained stable in the other four rhesus macaques. Although these animals had about 100-fold reduced viral RNA loads relative to 239wt-infected macaques, they showed pronounced CD4 T-cell depletion in the intestinal lamina propria, and one developed opportunistic infections and died with simian AIDS. Thus, changes in the V3 loop that diminished CCR5 usage and altered Env interactions with CCR5 reduced the pathogenic potential of SIVmac in rhesus macaques but did not abolish it entirely. © 2006 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/157476
ISSN
2023 Impact Factor: 2.8
2023 SCImago Journal Rankings: 0.838
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPöhlmann, Sen_US
dc.contributor.authorMünch, Jen_US
dc.contributor.authorAziz, Sen_US
dc.contributor.authorReeves, JDen_US
dc.contributor.authorOtto, Cen_US
dc.contributor.authorLeslie, GJen_US
dc.contributor.authorHofmann, Hen_US
dc.contributor.authorPuffer, BAen_US
dc.contributor.authorBaribaud, Fen_US
dc.contributor.authorMarzi, Aen_US
dc.contributor.authorGramberg, Ten_US
dc.contributor.authorChen, Zen_US
dc.contributor.authorStolte, Nen_US
dc.contributor.authorHaaft, PTen_US
dc.contributor.authorHeeney, JLen_US
dc.contributor.authorStahlHennig, Cen_US
dc.contributor.authorMätzRensing, Ken_US
dc.contributor.authorSchneider, Ten_US
dc.contributor.authorDoms, RWen_US
dc.contributor.authorKirchhoff, Fen_US
dc.date.accessioned2012-08-08T08:50:19Z-
dc.date.available2012-08-08T08:50:19Z-
dc.date.issued2007en_US
dc.identifier.citationVirology, 2007, v. 360 n. 2, p. 275-285en_US
dc.identifier.issn0042-6822en_US
dc.identifier.urihttp://hdl.handle.net/10722/157476-
dc.description.abstractSexually transmitted HIV-1 strains utilize the chemokine receptor CCR5 for viral entry and inhibitors targeting this coreceptor offer great promise for antiretroviral therapy. They also raise the question, however, whether viral variants exhibiting altered coreceptor interactions and resistance against these antiviral agents might still be pathogenic. In the present study, we analyzed a SIVmac239 envelope (Env) mutant (239DL) containing two mutations in the V3 loop which reduced viral entry via CCR5 by 10- to 20-fold, disrupted utilization of common alternative SIV coreceptors and changed the way Env engaged CCR5. To evaluate its replicative capacity and pathogenic potential in vivo we infected six rhesus macaques with 239DL. We found that 239DL replication was only slightly attenuated early during infection. Thereafter, a D324V change, which restored efficient CCR5 usage and coincided with 239wt-like levels of viral replication, emerged in two animals. In contrast, the viral geno- and phenotype remained stable in the other four rhesus macaques. Although these animals had about 100-fold reduced viral RNA loads relative to 239wt-infected macaques, they showed pronounced CD4 T-cell depletion in the intestinal lamina propria, and one developed opportunistic infections and died with simian AIDS. Thus, changes in the V3 loop that diminished CCR5 usage and altered Env interactions with CCR5 reduced the pathogenic potential of SIVmac in rhesus macaques but did not abolish it entirely. © 2006 Elsevier Inc. All rights reserved.en_US
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yviroen_US
dc.relation.ispartofVirologyen_US
dc.subjectCCR5-
dc.subjectCoreceptor-
dc.subjectPathogenesis-
dc.subjectSIV-
dc.subjectTAK-779-
dc.subject.meshAnimalsen_US
dc.subject.meshCd4 Lymphocyte Counten_US
dc.subject.meshCell Lineen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshGene Products, Env - Genetics - Physiologyen_US
dc.subject.meshIntestines - Immunologyen_US
dc.subject.meshLeukocytes, Mononuclear - Virologyen_US
dc.subject.meshMacaca Mulattaen_US
dc.subject.meshMucous Membrane - Immunologyen_US
dc.subject.meshMutationen_US
dc.subject.meshRna, Viral - Blooden_US
dc.subject.meshReceptors, Ccr5 - Metabolismen_US
dc.subject.meshReceptors, Hiv - Metabolismen_US
dc.subject.meshSimian Acquired Immunodeficiency Syndrome - Virologyen_US
dc.subject.meshSimian Immunodeficiency Virus - Genetics - Pathogenicity - Physiologyen_US
dc.subject.meshViral Loaden_US
dc.subject.meshViremiaen_US
dc.subject.meshVirus Internalizationen_US
dc.subject.meshVirus Replicationen_US
dc.titleA simian immunodeficiency virus V3 loop mutant that does not efficiently use CCR5 or common alternative coreceptors is moderately attenuated in vivoen_US
dc.typeArticleen_US
dc.identifier.emailChen, Z:zchenai@hkucc.hku.hken_US
dc.identifier.authorityChen, Z=rp00243en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.virol.2006.10.020en_US
dc.identifier.pmid17126374-
dc.identifier.scopuseid_2-s2.0-33947604539en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33947604539&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume360en_US
dc.identifier.issue2en_US
dc.identifier.spage275en_US
dc.identifier.epage285en_US
dc.identifier.isiWOS:000245566100004-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridPöhlmann, S=7003508167en_US
dc.identifier.scopusauthoridMünch, J=7102005157en_US
dc.identifier.scopusauthoridAziz, S=15767073800en_US
dc.identifier.scopusauthoridReeves, JD=7403190121en_US
dc.identifier.scopusauthoridOtto, C=7202696590en_US
dc.identifier.scopusauthoridLeslie, GJ=7102173674en_US
dc.identifier.scopusauthoridHofmann, H=35320035600en_US
dc.identifier.scopusauthoridPuffer, BA=6602414258en_US
dc.identifier.scopusauthoridBaribaud, F=6602132353en_US
dc.identifier.scopusauthoridMarzi, A=8832647400en_US
dc.identifier.scopusauthoridGramberg, T=8135783000en_US
dc.identifier.scopusauthoridChen, Z=35271180800en_US
dc.identifier.scopusauthoridStolte, N=6603945372en_US
dc.identifier.scopusauthoridHaaft, PT=6506228781en_US
dc.identifier.scopusauthoridHeeney, JL=7005843527en_US
dc.identifier.scopusauthoridStahlHennig, C=7005711034en_US
dc.identifier.scopusauthoridMätzRensing, K=7004612423en_US
dc.identifier.scopusauthoridSchneider, T=7401835859en_US
dc.identifier.scopusauthoridDoms, RW=7007070550en_US
dc.identifier.scopusauthoridKirchhoff, F=7005249256en_US
dc.identifier.issnl0042-6822-

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