Retrocyclin: a primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1.
Human bone marrow expresses a pseudogene that encodes an antimicrobial peptide homologous to rhesus monkey circular minidefensins (delta-defensins). We prepared the putative ancestral human peptide by solid-phase synthesis and named it "retrocyclin." Retrocyclin did not cause direct inactivation of HIV-1, and its modest antibacterial properties resembled those of its rhesus homologs. Nevertheless, retrocyclin had a remarkable ability to inhibit proviral DNA formation and to protect immortalized and primary human CD4(+) lymphocytes from in vitro infection by both T-tropic and M-tropic strains of HIV-1. Confocal fluorescent microscopy studies performed with BODIPY-FL-labeled RC-101, a close analog of retrocyclin, showed that the peptide formed patch-like aggregates on the surface of CD4(+) cells. These findings suggest that retrocyclin interferes with an early stage of HIV-1 infection and that retrocyclin-like agents might be useful topical agents to prevent sexually acquired HIV-1 infections.
Cole
Alexander M
AM
Department of Medicine, AIDS Institute, University of California School of Medicine, Los Angeles, CA 90095, USA.
Hong
Teresa
T
Boo
Lee Ming
LM
Nguyen
Tung
T
Zhao
Chengquan
C
Bristol
Greg
G
Zack
Jerome A
JA
Waring
Alan J
AJ
Yang
Otto O
OO
Lehrer
Robert I
RI
D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000378:metabolism*; D001896:Boron Compounds / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology*; D002942:Circular Dichroism; D018076:DNA, Complementary / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D023082:Defensins / Q000737:chemistry* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008253:Macaca mulatta; D018613:Microscopy, Confocal; D008954:Models, Biological; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012492:Salts / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013997:Time Factors
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D018076:DNA, Complementary; D004279:DNA, Viral; D023082:Defensins; D016376:Oligonucleotides, Antisense; D010455:Peptides; D011506:Proteins; C450143:RC 101; D012492:Salts; C450142:theta-defensin