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 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.
Dettin
M
M
Department of Chemical Process Engineering, University of Padova, 35131 Padova, Italy. monica.dettin@unipd.it
Zanchetta
M
M
Pasquato
A
A
Borrello
M
M
Piatier-Tonneau
D
D
Di Bello
C
C
De Rossi
A
A
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000737:chemistry*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015854:Up-Regulation
D015704:CD4 Antigens; D010455:Peptides; D019713:Receptors, CCR5; D019718:Receptors, CXCR4