Title
RC-101, a retrocyclin-1 analogue with enhanced activity against primary HIV type 1 isolates
Abbreviated Journal Title
Aids Res. Hum. Retrovir.
Keywords
IMMUNODEFICIENCY-VIRUS TYPE-1; HERPES-SIMPLEX-VIRUS; ANTIMICROBIAL; PEPTIDES; ALPHA-DEFENSINS; BETA-DEFENSINS; THETA-DEFENSINS; HUMAN; ALPHA-DEFENSIN-1; MESSENGER-RNA; HOST-DEFENSE; SUBTYPE-C; Immunology; Infectious Diseases; Virology
Abstract
Rhesus macaques express three theta-defensins (RTDs 1-3), cyclic octadecapeptides with antiviral and lectin-like properties. Corresponding theta-defensin genes exist and are expressed in humans, but a signal sequence mutation prevents the formation of mature theta-defensin peptides. Retrocyclin-1 is a theta-defensin peptide whose precursor is encoded by human theta-defensin pseudogenes. It can protect human peripheral blood lymphocytes from infection by R5 and X4 strains of HIV-1, and provides a molecular template for designing novel antiviral agents. In this study, we used JC53-BL reporter cells to assess the activity of retrocyclin-1 (RC-100) and several analogues against primary HIV-1 isolates, including R5 and R5X4 strains of subtypes A-D, CRF-01_AE, and recombinants. Each analogue differed from retrocyclin-1 by a single amino, acid substitution: Gly -- > Tyr in RC-106, RC-115, and RC-116, and Arg -- > Lys in RC-101. Although the modification in RC-101 was chemically conservative, this peptide was significantly more potent than retrocyclin-1 across the panel of primary isolates. We performed surface plasmon resonance binding studies, using recombinant gp120 and CD4 produced in insect cells. Although RC-100 and RC-101 bound gp120 LAV/IIIB with a K-d of 30-35 nM, they bound gp120 from CRF-01_AE strains (CM 235 and 93TH975.15) with K-d values of 200-750 nM. Overall, our findings suggest that clade-related differences in gp120 glycosylation impact the ability of retrocyclin-1 to bind this viral glycoprotein, and modulate the peptides' ability to prevent HIV-1 infection. The performance of RC-101 suggests that additional "engineering" could further enhance the antiviral properties of theta-defensins.
Journal Title
Aids Research and Human Retroviruses
Volume
20
Issue/Number
11
Publication Date
1-1-2004
Document Type
Article
Language
English
First Page
1157
Last Page
1165
WOS Identifier
ISSN
0889-2229
Recommended Citation
"RC-101, a retrocyclin-1 analogue with enhanced activity against primary HIV type 1 isolates" (2004). Faculty Bibliography 2000s. 4624.
https://stars.library.ucf.edu/facultybib2000/4624
Comments
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