title: Peptide-derivatized SB105-A10 dendrimer inhibits the infectivity of R5 and X4 HIV-1 strains in primary PBMCs and cervicovaginal histocultures.
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.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Microbiology Section, University of Bologna, Bologna, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Bon
authors.forename: David
authors.initials: D
authors.lastname: Lembo
authors.forename: Marco
authors.initials: M
authors.lastname: Rusnati
authors.forename: Alberto
authors.initials: A
authors.lastname: Clò
authors.forename: Silvia
authors.initials: S
authors.lastname: Morini
authors.forename: Anna
authors.initials: A
authors.lastname: Miserocchi
authors.forename: Antonella
authors.initials: A
authors.lastname: Bugatti
authors.forename: Sonia
authors.initials: S
authors.lastname: Grigolon
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Musumeci
authors.forename: Santo
authors.initials: S
authors.lastname: Landolfo
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Re
authors.forename: Davide
authors.initials: D
authors.lastname: Gibellini
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D002584:Cervix Uteri / Q000187:drug effects* / Q000821:virology; D050091:Dendrimers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000821:virology; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D013045:Species Specificity; D046509:Tissue Culture Techniques; D014621:Vagina / Q000187:drug effects* / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D050091:Dendrimers; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D010455:Peptides; C000590113:SB105-A10; C514787:gp41 protein, Human immunodeficiency virus 1