Peptide dendrimers are a class of molecules that exhibit a large array of biological effects including antiviral activity. In this report, we analyzed the antiviral activity of the peptide-derivatized SB105-A10 dendrimer, which is a tetra-branched dendrimer synthetized on a lysine core, in activated peripheral blood mononuclear cells (PBMCs) that were challenged with reference and wild-type human immunodeficiency virus type 1 (HIV-1) strains. SB105-A10 inhibited infections by HIV-1 X4 and R5 strains, interfering with the early phases of the viral replication cycle. SB105-A10 targets heparan sulfate proteoglycans (HSPGs) and, importantly, the surface plasmon resonance (SPR) assay revealed that SB105-A10 strongly binds gp41 and gp120, most likely preventing HIV-1 attachment/entry through multiple mechanisms. Interestingly, the antiviral activity of SB105-A10 was also detectable in an organ-like structure of human cervicovaginal tissue, in which SB105-A10 inhibited the HIV-1ada R5 strain infection without altering the tissue viability. These results demonstrated the strong antiviral activity of SB105-A10 and suggest a potential microbicide use of this dendrimer to prevent the heterosexual transmission of HIV-1.

Peptide-Derivatized SB105-A10 Dendrimer Inhibits the Infectivity of R5 and X4 HIV-1 Strains in Primary PBMCs and Cervicovaginal Histocultures.

LEMBO, David;LANDOLFO, Santo Giuseppe;
2013-01-01

Abstract

Peptide dendrimers are a class of molecules that exhibit a large array of biological effects including antiviral activity. In this report, we analyzed the antiviral activity of the peptide-derivatized SB105-A10 dendrimer, which is a tetra-branched dendrimer synthetized on a lysine core, in activated peripheral blood mononuclear cells (PBMCs) that were challenged with reference and wild-type human immunodeficiency virus type 1 (HIV-1) strains. SB105-A10 inhibited infections by HIV-1 X4 and R5 strains, interfering with the early phases of the viral replication cycle. SB105-A10 targets heparan sulfate proteoglycans (HSPGs) and, importantly, the surface plasmon resonance (SPR) assay revealed that SB105-A10 strongly binds gp41 and gp120, most likely preventing HIV-1 attachment/entry through multiple mechanisms. Interestingly, the antiviral activity of SB105-A10 was also detectable in an organ-like structure of human cervicovaginal tissue, in which SB105-A10 inhibited the HIV-1ada R5 strain infection without altering the tissue viability. These results demonstrated the strong antiviral activity of SB105-A10 and suggest a potential microbicide use of this dendrimer to prevent the heterosexual transmission of HIV-1.
8
10
e76482
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0076482
Anti-HIV Agents; peptide
Amino Acid Sequence; Antiviral Agents; Cervix Uteri; Dendrimers; Female; Flow Cytometry; HIV Envelope Protein gp120; HIV Envelope Protein gp41; HIV Infections; HIV-1; Host-Pathogen Interactions; Humans; Leukocytes, Mononuclear; Molecular Structure; Peptides; Protein Binding; Species Specificity; Tissue Culture Techniques; Vagina; Virus Replication; Agricultural and Biological Sciences (all); Biochemistry, Genetics and Molecular Biology (all); Medicine (all)
Bon I; Lembo D; Rusnati M; Clò A; Morini S; Miserocchi A; Bugatti A; Grigolon S; Musumeci G; Landolfo S; Re MC; Gibellini D.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/139097
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