Paradoxical effects of two theta-defensins on HIV type 1 infection.
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.
Wang
Qiuwei
Q
UCLA School of Dentistry, and Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Wang
Wei
W
Zheng
Junying
J
Tabibian
Sina
S
Xie
Yiming
Y
Song
Jun
J
Waring
Alan J
AJ
Chiu
Robert
R
Yang
Otto O
OO
Chen
Irvin S Y
IS
Lehrer
Robert I
RI
Pang
Shen
S
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002461:Cell Line, Transformed; D023082:Defensins / Q000819:agonists / Q000737:chemistry / Q000494:pharmacology*; D004847:Epithelial Cells / Q000821:virology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000196:embryology; D009457:Neuroglia / Q000821:virology*
D023082:Defensins; C450142:theta-defensin