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Peptide T inhibits HIV-1 infection mediated by the chemokine receptor-5 (CCR5)

  1. Author:
    Ruff, M. R.
    Melendez-Guerrero, L. M.
    Yang, Q. E.
    Ho, W. Z.
    Mikovits, J. W.
    Pert, C. B.
    Ruscetti, F. A.
  2. Author Address

    Georgetown Univ, Sch Med, Dept Physiol & Biophys, Basic Sci Bldg, Room 215, 3900 Reservoir Rd NW, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. Univ Puerto Rico, Sch Med, Dept Microbiol & Med Zool, San Juan, PR 00936 USA. NCI, Lab Antiviral Drug Mechanisms, Screening Technol Branch, FCRDC, Ft Detrick, MD 21702 USA. Childrens Hosp Philadelphia, Div Immunol & Infect Dis, Philadelphia, PA 19104 USA. NCI, Leukocyte Biol Sect, Canc Res Ctr, FCRDC, Frederick, MD 21702 USA. Ruff MR Georgetown Univ, Sch Med, Dept Physiol & Biophys, Basic Sci Bldg, Room 215, 3900 Reservoir Rd NW, Washington, DC 20007 USA.
    1. Year: 2001
  1. Journal: Antiviral Research
    1. 52
    2. 1
    3. Pages: 63-75
  2. Type of Article: Article
  1. Abstract:

    Peptide T, which is derived from the V2 region of HIV-1, inhibits replication of R5 and dual-tropic (R5/X4) HIV-1 strains in monocyte-derived macrophages (MDMs), microglia, and primary CD4(+) T cells. Little to no inhibition by peptide T was observed with lab adapted X4 viruses such as IIIB. MN. or NL4-3 propagated in CD4(+) T cells or in the MAGI entry assay. The more clinically relevant R5/X4 early passage patient isolates were inhibited via either the X4 or R5 chemokine receptors, although inhibition was greater with R5 compared to X4 receptors. Virus inhibition ranged from 60 to 99%, depending on the assay, receptor target, viral isolate and amount of added virus. Peak inhibitory effects were detected at concentrations from 10(-12) to 10(-9) M. Peptide T acted to block viral entry as it inhibited in the MAGI cell assay and blocked infection in the luciferase reporter assay using HIV virions pseudotyped with ADA envelope. These results using early passage virus grown in primary cells, together with two different entry reporter assays, show that peptide T selectively inhibits HIV replication using chemokine receptor CCR5 compared to CXC4, explaining past inconsistencies of in vitro antiviral effects. (C) 2001 Elsevier Science B.V. All rights reserved.

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