| Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. | |
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MedLine Citation:
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PMID: 20494390 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The V3 region of the HIV-1 envelope (Env) glycoprotein gp120 is a key functional domain yet it exhibits distinct mutational patterns across subtypes. Here an invariant residue (Ile 309) was replaced with Leu in 7 subtype C patient-derived Envs from recent infection and 4 related neutralizing antibody escape variants that emerged later. For these 11 Envs, I309L did not alter replication in primary CD4 T cells; however, replication in monocyte-derived macrophages was enhanced. Infection of cell lines with low CD4 or CCR5 revealed that I309L enhanced utilization of CD4 but did not affect the ability to use CCR5. This CD4-enhanced phenotype tracked with sensitivity to sCD4, indicating increased exposure of the CD4 binding site. The results suggest that Ile 309 preserves a V3-mediated masking function that occludes the CD4 binding site. The findings point to an immune evasion strategy in subtype C Env to protect this vulnerable immune target. |
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Authors:
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Rebecca M Lynch; Rong Rong; Bing Li; Tongye Shen; William Honnen; Joseph Mulenga; Susan Allen; Abraham Pinter; S Gnanakaran; Cynthia A Derdeyn |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-05-21 |
Journal Detail:
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Title: Virology Volume: 404 ISSN: 1096-0341 ISO Abbreviation: Virology Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-06-14 Completed Date: 2010-06-29 Revised Date: 2010-12-17 |
Medline Journal Info:
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Nlm Unique ID: 0110674 Medline TA: Virology Country: United States |
Other Details:
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Languages: eng Pagination: 59-70 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, GA 30329, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Substitution
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genetics Antigens, CD4 / metabolism CD4-Positive T-Lymphocytes / virology Conserved Sequence* Female Genotype HIV Envelope Protein gp120 / genetics, immunology*, physiology* HIV-1 / genetics, growth & development, immunology*, pathogenicity* Humans Immune Evasion* Isoleucine / genetics* Macrophages / virology Male Mutagenesis, Site-Directed Receptors, CCR5 / metabolism Receptors, HIV / metabolism Virulence Factors / genetics, immunology, physiology Virus Replication |
| Grant Support | |
ID/Acronym/Agency:
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AI27742/AI/NIAID NIH HHS; AI58706/AI/NIAID NIH HHS; AI78410/AI/NIAID NIH HHS; R01 AI058706-09/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD4; 0/HIV Envelope Protein gp120; 0/Receptors, CCR5; 0/Receptors, HIV; 0/Virulence Factors; 0/gp120 protein, Human immunodeficiency virus 1; 73-32-5/Isoleucine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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