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AIDS Res Hum Retroviruses. 2007 Apr;23(4):508-14.

Paradoxical effects of two theta-defensins on HIV type 1 infection.

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1
UCLA School of Dentistry, and Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA 90095, USA.

Abstract

Retrocyclin-1 (RC-100) is a cyclic octadecapeptide whose primary structure is based on the sequence of an expressed human theta-defensin pseudogene. RC-111 has the same amino acid sequence as RC-100 and is also cyclic, but its residues are placed in reverse order along the peptide's backbone. We quantified the effects of RC-100 and RC-111 on HIV-1 infection using HIV clones that expressed green fluorescent protein. Whereas 0.2 microg/ml of RC-100 inhibited infection of CD4-positive cells by approximately 80%, its retro-analogue significantly enhanced infection of the cells. RC-100 and RC-111 also demonstrate their effects in HIV infection of CD4-negative cells. Whereas 40 ng/ml of RC-111 significantly enhanced infection of CD4-negative cells by HIV-1, RC-100 demonstrated significant inhibition of HIV infection with a concentration of approximately 10 microg/ml. RC-111ox, an acyclic variant of RC-111 with a beta-hairpin structure, also enhanced HIV-1 infection, but did so less effectively than cyclic RC-111. The divergent actions of RC-100 and RC-111 show that topology and polarity of theta-defensin peptides can determine their effect on HIV infection. The ability of RC-111 to enhance HIV-1 infection might prove useful in developing peptides that can enhance gene delivery by HIV-based lentiviral vectors.

PMID:
17506607
DOI:
10.1089/aid.2006.0119
[Indexed for MEDLINE]

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