CCR5 N-terminus peptides enhance X4 HIV-1 infection by CXCR4 up-regulation

The HIV-1 envelope glycoprotein gp120 interacts consecutively with CD4 and CCR5 to mediate the entry of R5-HIV-1 strains into target cells. The N-terminus of CCR5, which contains several sulfated tyrosines, plays a critical role in gp120–CCR5 binding and, consequently, in viral entry. Here, we demon...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2003-08, Vol.307 (3), p.640-646
Main Authors: Dettin, M, Zanchetta, M, Pasquato, A, Borrello, M, Piatier-Tonneau, D, Di Bello, C, De Rossi, A
Format: Article
Language:English
Subjects:
AIDS
Amino Acid Sequence
Animals
CCR5
CD4
CD4 Antigens - metabolism
Cell Line
CXCR4
Dose-Response Relationship, Drug
gp120
HIV Infections - immunology
HIV-1
HIV-1 - pathogenicity
Molecular Sequence Data
Peptide
Peptides - chemistry
Peptides - pharmacology
Receptors, CCR5 - chemistry
Receptors, CXCR4 - metabolism
Sulfated tyrosines
Up-Regulation
Viral entry
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Summary:The HIV-1 envelope glycoprotein gp120 interacts consecutively with CD4 and CCR5 to mediate the entry of R5-HIV-1 strains into target cells. The N-terminus of CCR5, which contains several sulfated tyrosines, plays a critical role in gp120–CCR5 binding and, consequently, in viral entry. Here, we demonstrate that a tyrosine sulfated peptide, reproducing the entire N-terminal extracellular region of CCR5, its unsulfated analogue, and a point-mutated peptide are unable to inhibit R5-HIV-1 mediated infection, competing with the entire CCR5 in the formation of gp120–CD4–CCR5 complex. Surprisingly, these peptides show the capability of enhancing HIV-1 infection caused by X4 strains through the up-regulation of both CD4 and CXCR4 receptors.
ISSN:0006-291X
1090-2104
DOI:10.1016/S0006-291X(03)01237-3