Abstract:
:The unexpected encounter between the fields of HIV and chemokines has opened new perspectives for understanding the mechanisms of AIDS pathogenesis, as well as for the development of effective therapies and vaccines. Selected chemokines act as potent natural inhibitors of HIV infection, as they bind and downmodulate chemokine receptors that serve as critical coreceptors for HIV to gain access into cells. The differential usage of the two major HIV coreceptors, CCR5 and CXCR4, determines the biological diversity among HIV variants. Most primary HIV strains use CCR5 as a coreceptor and thereby are sensitive to inhibition by the CCR5-ligand chemokines, RANTES, MIP-1alpha and MIP-1beta. The high level of expression of these proinflammatory chemokines in HIV-infected secondary lymphoid tissues may help to explain the inherently slow course of HIV disease. The crucial role played by CCR5 in the physiology of HIV infection is further attested by the near-complete resistance to HIV infection in people carrying a homozygous 32 bp deletion within the CCR5 gene (CCR5-delta32). A smaller proportion of HIV isolates, commonly emerging in concomitance with the clinical progression toward AIDS, uses CXCR4 as a coreceptor and is inhibited by the CXCR4 ligand, SDF-1. The high level of expresion of SDF-1 in the genital mucosa may help to explain the inefficient transmission of CXCR4-tropic HIV. Although chemokines or derivative-molecules could be exploited as therapeutic agents against HIV, the risk of inducing inflammatory side-effects or of interfering with the physiology of the homeostatic chemokine system represents a potential limitation. However, the ability of chemokines to block HIV infection can be uncoupled from their receptor-mediated signaling activity, thus providing a theoretical foundation for the rational design of safe and effective chemokine receptor inhibitors.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Verani A,Lusso Pdoi
10.2174/1566524023361862keywords:
subject
Has Abstractpub_date
2002-12-01 00:00:00pages
691-702issue
8eissn
1566-5240issn
1875-5666journal_volume
2pub_type
杂志文章,评审abstract::The world is aging and we must face the challenges that this brings. One of the reasons for the increasing aging of the world's population is the increase in life expectancy and, since we live longer, it is of paramount importance to live well and to prevent age-associated diseases. In this way, it is crucial to impro...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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pub_type: 杂志文章,多中心研究
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更新日期:2011-03-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
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journal_title:Current molecular medicine
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更新日期:2020-01-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2008-11-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200123161340
更新日期:2020-01-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190918160032
更新日期:2019-01-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2005-11-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2012-09-01 00:00:00
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pub_type: 杂志文章
doi:10.2174/1566524019666190509102620
更新日期:2019-01-01 00:00:00
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journal_title:Current molecular medicine
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更新日期:2014-01-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2008-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2021-01-10 00:00:00
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更新日期:2012-12-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2010-02-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2003-05-01 00:00:00
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更新日期:2001-05-01 00:00:00
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更新日期:2007-08-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2011-07-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
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journal_title:Current molecular medicine
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doi:10.2174/156652407779940503
更新日期:2007-02-01 00:00:00