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Natural Infection of a Homozygous Δ24 CCR5 Red-capped Mangabey with an R2b-Tropic Simian Immunodeficiency Virus

A homozygous 24-bp deletion (Δ24) was found in the CC chemokine receptor 5 (CCR5) of 11 out of 15 red-capped mangabeys (RCMs), Cercocebus torquatus torquatus, both in Africa and in an American zoo. The CCR5 Δ24 defect encompassed eight amino acids in frame in the fourth transmembrane region. Unexpec...

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Autores principales: Chen, Zhiwei, Kwon, Douglas, Jin, Zhanqun, Monard, Simon, Telfer, Paul, Jones, Morris S., Lu, Chang Y., Aguilar, Roberto F., Ho, David D., Marx, Preston A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212380/
https://www.ncbi.nlm.nih.gov/pubmed/9841919
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author Chen, Zhiwei
Kwon, Douglas
Jin, Zhanqun
Monard, Simon
Telfer, Paul
Jones, Morris S.
Lu, Chang Y.
Aguilar, Roberto F.
Ho, David D.
Marx, Preston A.
author_facet Chen, Zhiwei
Kwon, Douglas
Jin, Zhanqun
Monard, Simon
Telfer, Paul
Jones, Morris S.
Lu, Chang Y.
Aguilar, Roberto F.
Ho, David D.
Marx, Preston A.
author_sort Chen, Zhiwei
collection PubMed
description A homozygous 24-bp deletion (Δ24) was found in the CC chemokine receptor 5 (CCR5) of 11 out of 15 red-capped mangabeys (RCMs), Cercocebus torquatus torquatus, both in Africa and in an American zoo. The CCR5 Δ24 defect encompassed eight amino acids in frame in the fourth transmembrane region. Unexpectedly, RCM-009, one of 11 homozygotes (Δ24CCR5/ Δ24CCR5), was found to be naturally infected with a divergent simian immunodeficiency virus (SIV) strain, which was not R5-tropic, but used CCR2b (R2b) as its major coreceptor. SIVrcmGab1 was the only R2b-tropic SIV among other divergent SIVs tested. Cells transfected with the Δ24 CCR5 did not support entry of R5-tropic SIVmac, SIVcpz, SIVmne, HIV-2, or HIV-1, and were also inactive in signal transduction mediated by β-chemokines. At 86.6%, the Δ24 allelic frequency was significantly higher than that of the 32-bp deletion found in humans. The Δ24 frequency was 4.1% in 34 sooty mangabeys (SMs), a geographically isolated subspecies that was naturally infected with R5-tropic SIV. Finding identical deletions in two mangabey subspecies separated for 10,000 years or more dates the Δ24 CCR5 deletion as ancient. However, the source of the selective pressure for the high rate of CCR5 deletion in RCMs remains to be determined. The high allelic frequency of the Δ24 CCR5 in RCMs, in comparison to that of SMs, suggests that R2b-tropism may have been acquired by SIVrcm, as an adaptation to CCR5 genetic defects appeared in its host.
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spelling pubmed-22123802008-04-16 Natural Infection of a Homozygous Δ24 CCR5 Red-capped Mangabey with an R2b-Tropic Simian Immunodeficiency Virus Chen, Zhiwei Kwon, Douglas Jin, Zhanqun Monard, Simon Telfer, Paul Jones, Morris S. Lu, Chang Y. Aguilar, Roberto F. Ho, David D. Marx, Preston A. J Exp Med Articles A homozygous 24-bp deletion (Δ24) was found in the CC chemokine receptor 5 (CCR5) of 11 out of 15 red-capped mangabeys (RCMs), Cercocebus torquatus torquatus, both in Africa and in an American zoo. The CCR5 Δ24 defect encompassed eight amino acids in frame in the fourth transmembrane region. Unexpectedly, RCM-009, one of 11 homozygotes (Δ24CCR5/ Δ24CCR5), was found to be naturally infected with a divergent simian immunodeficiency virus (SIV) strain, which was not R5-tropic, but used CCR2b (R2b) as its major coreceptor. SIVrcmGab1 was the only R2b-tropic SIV among other divergent SIVs tested. Cells transfected with the Δ24 CCR5 did not support entry of R5-tropic SIVmac, SIVcpz, SIVmne, HIV-2, or HIV-1, and were also inactive in signal transduction mediated by β-chemokines. At 86.6%, the Δ24 allelic frequency was significantly higher than that of the 32-bp deletion found in humans. The Δ24 frequency was 4.1% in 34 sooty mangabeys (SMs), a geographically isolated subspecies that was naturally infected with R5-tropic SIV. Finding identical deletions in two mangabey subspecies separated for 10,000 years or more dates the Δ24 CCR5 deletion as ancient. However, the source of the selective pressure for the high rate of CCR5 deletion in RCMs remains to be determined. The high allelic frequency of the Δ24 CCR5 in RCMs, in comparison to that of SMs, suggests that R2b-tropism may have been acquired by SIVrcm, as an adaptation to CCR5 genetic defects appeared in its host. The Rockefeller University Press 1998-12-07 /pmc/articles/PMC2212380/ /pubmed/9841919 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Chen, Zhiwei
Kwon, Douglas
Jin, Zhanqun
Monard, Simon
Telfer, Paul
Jones, Morris S.
Lu, Chang Y.
Aguilar, Roberto F.
Ho, David D.
Marx, Preston A.
Natural Infection of a Homozygous Δ24 CCR5 Red-capped Mangabey with an R2b-Tropic Simian Immunodeficiency Virus
title Natural Infection of a Homozygous Δ24 CCR5 Red-capped Mangabey with an R2b-Tropic Simian Immunodeficiency Virus
title_full Natural Infection of a Homozygous Δ24 CCR5 Red-capped Mangabey with an R2b-Tropic Simian Immunodeficiency Virus
title_fullStr Natural Infection of a Homozygous Δ24 CCR5 Red-capped Mangabey with an R2b-Tropic Simian Immunodeficiency Virus
title_full_unstemmed Natural Infection of a Homozygous Δ24 CCR5 Red-capped Mangabey with an R2b-Tropic Simian Immunodeficiency Virus
title_short Natural Infection of a Homozygous Δ24 CCR5 Red-capped Mangabey with an R2b-Tropic Simian Immunodeficiency Virus
title_sort natural infection of a homozygous δ24 ccr5 red-capped mangabey with an r2b-tropic simian immunodeficiency virus
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212380/
https://www.ncbi.nlm.nih.gov/pubmed/9841919
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