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- Publisher Website: 10.1016/S0960-9822(07)00378-8
- Scopus: eid_2-s2.0-13144262804
- PMID: 9707408
- WOS: WOS:000075262100023
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Article: Parallel evolution of CCR5-null phenotypes in humans and in a natural host of simian immunodeficiency virus
Title | Parallel evolution of CCR5-null phenotypes in humans and in a natural host of simian immunodeficiency virus |
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Authors | |
Issue Date | 1998 |
Publisher | Cell 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? |
Abstract | The 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 Identifier | http://hdl.handle.net/10722/157391 |
ISSN | 2023 Impact Factor: 8.1 2023 SCImago Journal Rankings: 2.982 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Palacios, E | en_US |
dc.contributor.author | Digilio, L | en_US |
dc.contributor.author | Mcclure, HM | en_US |
dc.contributor.author | Chen, Z | en_US |
dc.contributor.author | Marx, PA | en_US |
dc.contributor.author | Goldsmith, MA | en_US |
dc.contributor.author | Grant, RM | en_US |
dc.date.accessioned | 2012-08-08T08:49:35Z | - |
dc.date.available | 2012-08-08T08:49:35Z | - |
dc.date.issued | 1998 | en_US |
dc.identifier.citation | Current Biology, 1998, v. 8 n. 16, p. 943-946 | en_US |
dc.identifier.issn | 0960-9822 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/157391 | - |
dc.description.abstract | The 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.language | eng | en_US |
dc.publisher | Cell Press. The Journal's web site is located at http://www.current-biology.com/ | en_US |
dc.relation.ispartof | Current Biology | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Antigens, Cd - Physiology | en_US |
dc.subject.mesh | Antigens, Cd4 - Physiology | en_US |
dc.subject.mesh | Cos Cells | en_US |
dc.subject.mesh | Cercocebus | en_US |
dc.subject.mesh | Hiv-1 - Physiology | en_US |
dc.subject.mesh | Heterozygote Detection | en_US |
dc.subject.mesh | Homozygote | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Macaca Mulatta | en_US |
dc.subject.mesh | Phenotype | en_US |
dc.subject.mesh | Receptors, Ccr5 - Deficiency - Genetics - Physiology | en_US |
dc.subject.mesh | Recombinant Proteins - Biosynthesis | en_US |
dc.subject.mesh | Sequence Deletion | en_US |
dc.subject.mesh | Simian Immunodeficiency Virus - Physiology | en_US |
dc.subject.mesh | Transfection | en_US |
dc.title | Parallel evolution of CCR5-null phenotypes in humans and in a natural host of simian immunodeficiency virus | en_US |
dc.type | Article | en_US |
dc.identifier.email | Chen, Z:zchenai@hkucc.hku.hk | en_US |
dc.identifier.authority | Chen, Z=rp00243 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1016/S0960-9822(07)00378-8 | - |
dc.identifier.pmid | 9707408 | - |
dc.identifier.scopus | eid_2-s2.0-13144262804 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-13144262804&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 8 | en_US |
dc.identifier.issue | 16 | en_US |
dc.identifier.spage | 943 | en_US |
dc.identifier.epage | 946 | en_US |
dc.identifier.isi | WOS:000075262100023 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Palacios, E=7102758992 | en_US |
dc.identifier.scopusauthorid | Digilio, L=6602258692 | en_US |
dc.identifier.scopusauthorid | McClure, HM=35463579000 | en_US |
dc.identifier.scopusauthorid | Chen, Z=35271180800 | en_US |
dc.identifier.scopusauthorid | Marx, PA=7102894750 | en_US |
dc.identifier.scopusauthorid | Goldsmith, MA=7201364736 | en_US |
dc.identifier.scopusauthorid | Grant, RM=7402006018 | en_US |
dc.identifier.issnl | 0960-9822 | - |