title: M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures.
abstract: Microbicides are considered a promising strategy for preventing human immunodeficiency virus (HIV-1) transmission and disease. In this report, we first analyzed the antiviral activity of the miniCD4 M48U1 peptide formulated in hydroxyethylcellulose (HEC) hydrogel in activated peripheral blood mononuclear cells (PBMCs) infected with R5- and X4-tropic HIV-1 strains. The results demonstrate that M48U1 prevented infection by several HIV-1 strains including laboratory strains, and HIV-1 subtype B and C strains isolated from the activated PBMCs of patients. M48U1 also inhibited infection by two HIV-1 transmitted/founder infectious molecular clones (pREJO.c/2864 and pTHRO.c/2626). In addition, M48U1 was administered in association with tenofovir, and these two antiretroviral drugs synergistically inhibited HIV-1 infection. In the next series of experiments, we tested M48U1 alone or in combination with tenofovir in HEC hydrogel with an organ-like structure mimicking human cervicovaginal tissue. We demonstrated a strong antiviral effect in absence of significant tissue toxicity. Together, these results indicate that co-treatment with M48U1 plus tenofovir is an effective antiviral strategy that may be used as a new topical microbicide to prevent HIV-1 transmission.
authors.affiliation: Department of Experimental, Diagnostics and Specialty Medicine (DIMES), Microbiology Section, University of Bologna, 40138 Bologna, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Musumeci
authors.affiliation: Department of Experimental, Diagnostics and Specialty Medicine (DIMES), Microbiology Section, University of Bologna, 40138 Bologna, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Bon
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Lembo
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cagno
authors.affiliation: Department of Experimental, Diagnostics and Specialty Medicine (DIMES), Microbiology Section, University of Bologna, 40138 Bologna, Italy.
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Re
authors.affiliation: Department of Diagnostics and Public Health, Microbiology and Virology Unit, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Signoretto
authors.affiliation: Department of Diagnostics and Public Health, Microbiology and Virology Unit, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Diani
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Lopalco
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pastori
authors.affiliation: CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Gif sur Yvette, F-91191, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Martin
authors.affiliation: Institut Galien Paris Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris Saclay, 5 rue J-B. Clément, 92296, Châtenay-Malabry cedex, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Ponchel
authors.affiliation: Department of Diagnostics and Public Health, Microbiology and Virology Unit, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gibellini
authors.affiliation: Institut Galien Paris Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris Saclay, 5 rue J-B. Clément, 92296, Châtenay-Malabry cedex, France.
authors.forename: Kawthar
authors.initials: K
authors.lastname: Bouchemal
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D004847:Epithelial Cells / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D000068698:Tenofovir / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D001688:Biological Products; D000068698:Tenofovir