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Article: Parallel evolution of CCR5-null phenotypes in humans and in a natural host of simian immunodeficiency virus

TitleParallel evolution of CCR5-null phenotypes in humans and in a natural host of simian immunodeficiency virus
Authors
Issue Date1998
PublisherCell Press. The Journal's web site is located at http://www.current-biology.com/
Citation
Current Biology, 1998, v. 8 n. 16, p. 943-946 How to Cite?
AbstractThe C-C chemokine receptor CCR5 in humans and rhesus macaques (Macaca mulatta) serves as the primary coreceptor for cellular entry by macrophagetropic strains of human immunodeficiency virus type 1 (HIV-1) and all reported strains of simian immunodeficiency virus (SIV) [1-6]. Humans homozygous for a 32 bp deletion allele of CCR5, resulting in a null phenotype, are highly resistant to infection by HIV-1 [7-9], prompting development of therapies and vaccines targeting CCR5. We now report a novel deletion allele of CCR5, with an allele frequency of 0.04, in sooty mangabey monkeys (Cercocebus torquatus atys), a natural host of SlY (SIVsmm) [10]. The mutant protein was not expressed at the cell surface and accordingly did not function as a vital coreceptor. Primary activated lymphocytes from mangabeys heterozygous for the deletion allele expressed significantly less CCR5 on the cell surface. Moreover, SIV seroprevalence and viremia were comparable among CCR5 heterozygotes and wild-type animals. Parallel evolution of CCR5-null alleles in humans and sooty mangabeys suggests that similar negative selection-pressures have acted against CCR5, as would occur during epidemics of infectious agents that require CCR5 for pathogenesis. Sooty mangabeys bred to homozygosity for the deletion allele will be useful for experimental studies on the context-dependent role of CCR5 in host defense and microbial pathogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/157391
ISSN
2015 Impact Factor: 8.983
2015 SCImago Journal Rankings: 4.729
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPalacios, Een_US
dc.contributor.authorDigilio, Len_US
dc.contributor.authorMcclure, HMen_US
dc.contributor.authorChen, Zen_US
dc.contributor.authorMarx, PAen_US
dc.contributor.authorGoldsmith, MAen_US
dc.contributor.authorGrant, RMen_US
dc.date.accessioned2012-08-08T08:49:35Z-
dc.date.available2012-08-08T08:49:35Z-
dc.date.issued1998en_US
dc.identifier.citationCurrent Biology, 1998, v. 8 n. 16, p. 943-946en_US
dc.identifier.issn0960-9822en_US
dc.identifier.urihttp://hdl.handle.net/10722/157391-
dc.description.abstractThe C-C chemokine receptor CCR5 in humans and rhesus macaques (Macaca mulatta) serves as the primary coreceptor for cellular entry by macrophagetropic strains of human immunodeficiency virus type 1 (HIV-1) and all reported strains of simian immunodeficiency virus (SIV) [1-6]. Humans homozygous for a 32 bp deletion allele of CCR5, resulting in a null phenotype, are highly resistant to infection by HIV-1 [7-9], prompting development of therapies and vaccines targeting CCR5. We now report a novel deletion allele of CCR5, with an allele frequency of 0.04, in sooty mangabey monkeys (Cercocebus torquatus atys), a natural host of SlY (SIVsmm) [10]. The mutant protein was not expressed at the cell surface and accordingly did not function as a vital coreceptor. Primary activated lymphocytes from mangabeys heterozygous for the deletion allele expressed significantly less CCR5 on the cell surface. Moreover, SIV seroprevalence and viremia were comparable among CCR5 heterozygotes and wild-type animals. Parallel evolution of CCR5-null alleles in humans and sooty mangabeys suggests that similar negative selection-pressures have acted against CCR5, as would occur during epidemics of infectious agents that require CCR5 for pathogenesis. Sooty mangabeys bred to homozygosity for the deletion allele will be useful for experimental studies on the context-dependent role of CCR5 in host defense and microbial pathogenesis.en_US
dc.languageengen_US
dc.publisherCell Press. The Journal's web site is located at http://www.current-biology.com/en_US
dc.relation.ispartofCurrent Biologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntigens, Cd - Physiologyen_US
dc.subject.meshAntigens, Cd4 - Physiologyen_US
dc.subject.meshCos Cellsen_US
dc.subject.meshCercocebusen_US
dc.subject.meshHiv-1 - Physiologyen_US
dc.subject.meshHeterozygote Detectionen_US
dc.subject.meshHomozygoteen_US
dc.subject.meshHumansen_US
dc.subject.meshMacaca Mulattaen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshReceptors, Ccr5 - Deficiency - Genetics - Physiologyen_US
dc.subject.meshRecombinant Proteins - Biosynthesisen_US
dc.subject.meshSequence Deletionen_US
dc.subject.meshSimian Immunodeficiency Virus - Physiologyen_US
dc.subject.meshTransfectionen_US
dc.titleParallel evolution of CCR5-null phenotypes in humans and in a natural host of simian immunodeficiency virusen_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.pmid9707408-
dc.identifier.scopuseid_2-s2.0-13144262804en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-13144262804&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume8en_US
dc.identifier.issue16en_US
dc.identifier.spage943en_US
dc.identifier.epage946en_US
dc.identifier.isiWOS:000075262100023-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridPalacios, E=7102758992en_US
dc.identifier.scopusauthoridDigilio, L=6602258692en_US
dc.identifier.scopusauthoridMcClure, HM=35463579000en_US
dc.identifier.scopusauthoridChen, Z=35271180800en_US
dc.identifier.scopusauthoridMarx, PA=7102894750en_US
dc.identifier.scopusauthoridGoldsmith, MA=7201364736en_US
dc.identifier.scopusauthoridGrant, RM=7402006018en_US

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