The theta-defensin, retrocyclin, inhibits HIV-1 entry

    Authors

    C. Munk; G. Wei; O. O. Yang; A. J. Waring; W. Wang; T. Hong; R. I. Lehrer; N. R. Landau;A. M. Cole

    Comments

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    Abbreviated Journal Title

    Aids Res. Hum. Retrovir.

    Keywords

    IMMUNODEFICIENCY-VIRUS TYPE-1; RHESUS-MACAQUE LEUKOCYTES; ANTIMICROBIAL; PEPTIDES; REPLICATION; CELLS; ANTIBIOTICS; INFECTION; FUSION; BLOCK; Immunology; Infectious Diseases; Virology

    Abstract

    Retrocyclin is a circular antimicrobial 18-residue peptide encoded in the human genome by a theta-defensin pseudogene. In the human genome, the gene for retrocyclin is inactivated by an in-frame stop codon in its signal sequence but its mature coding sequence is intact. The peptide corresponding to the processed human retrocyclin, generated by solid phase peptide synthesis, inhibited replication of R5 and X4 strains of HIV-1 in human cells. Luciferase reporter virus and Vpr-BLaM entry assays were used to demonstrate that retrocyclin specifically blocked R5 and X4 HIV-1 replication at entry. Surface plasmon resonance demonstrated that retrocyclin bound to soluble CD4 and gp120, but gp120 cell-binding assays revealed that retrocyclin did not fully inhibit the binding of soluble CD4 to gp120. A fluorescent retrocyclin congener localized in cell-surface patches either alone or colocalized with CD4, CXCR4, and CCR5. In the aggregate, these results suggest that retrocyclin blocks an entry step in HIV-1 replication. Retrocyclin represents a new class of small molecule HIV-1 entry inhibitors.

    Journal Title

    Aids Research and Human Retroviruses

    Volume

    19

    Issue/Number

    10

    Publication Date

    1-1-2003

    Document Type

    Article

    Language

    English

    First Page

    875

    Last Page

    881

    WOS Identifier

    WOS:000186175100005

    ISSN

    0889-2229

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