title: 5-Hydroxytyrosol inhibits HIV-1 replication in primary cells of the lower and upper female reproductive tract.
abstract: We investigated the potential anti-HIV-1 activity of the candidate microbicide 5-hydroxytyrosol (5-HT) both in primary human cervical tissue explants (CTE), established from tissues of women undergoing histerectomy, and in endometrium-associated leukocytes (EAL). CTE were exposed to either the laboratory-adapted HIV-1BaLor to primary viral isolates in the presence or absence of 5-HT or 3TC/lamivudine as control and were then monitored for 12 days in terms of HIV-1 p24 Gag antigen production in culture supernatants. HIV-1BaLreplication was also evaluated in EAL by reverse transcriptase (RT) activity. The highest nontoxic concentrations of 5-HT (200 and 100 μM for CTE and EAL, respectively) exerted a significant inhibitory effect on virus replication in both primary cell systems. 5-HT did not cause significant alterations of the activation profile of CD4+and CD8+T cells, in terms of CD4, CCR5, CD25, CD69 and HLA-DR expression, although it decreased the percentage of CD38+CD8+T cells. Thus, 5-HT deserves consideration as a potential candidate microbicide for preventing HIV-1 transmission or curtailing its replication in the female reproductive tract.
authors.affiliation: AIDS Immunopathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy. Electronic address: elisa.saba@gmail.com.
authors.forename: Elisa
authors.initials: E
authors.lastname: Saba
authors.affiliation: Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy. Electronic address: panina.paola@hsr.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Panina-Bordignon
authors.affiliation: Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy. Electronic address: pagani.isabel@hsr.it.
authors.forename: Isabel
authors.initials: I
authors.lastname: Pagani
authors.affiliation: Department of Obstetrics and Gynecology, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy; Vita-Salute San Raffaele University, School of Medicine, Via Olgettina 58, 20132, Milano, Italy. Electronic address: origoni.massimo@hsr.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Origoni
authors.affiliation: Department of Obstetrics and Gynecology, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy; Vita-Salute San Raffaele University, School of Medicine, Via Olgettina 58, 20132, Milano, Italy. Electronic address: candiani.massimo@hsr.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Candiani
authors.affiliation: Vita-Salute San Raffaele University, School of Medicine, Via Olgettina 58, 20132, Milano, Italy; Pathology Unit, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy. Electronic address: doglioni.claudio@hsr.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.affiliation: Pathology Unit, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy. Electronic address: taccagni.gianluca@hsr.it.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Taccagni
authors.affiliation: Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy. Electronic address: ghezzi.silvia@hsr.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ghezzi
authors.affiliation: AIDS Immunopathology Department, National Centre of Microbiology, Instituto de Salud Carlos III. Cra Majadahonda a Pozuelo, 28220, Majadahonda, Madrid, Spain. Electronic address: ppalcami@isciii.es.
authors.forename: José
authors.initials: J
authors.lastname: Alcami
authors.affiliation: Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy. Electronic address: vicenzi.elisa@hsr.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Vicenzi
authors.affiliation: AIDS Immunopathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy; Vita-Salute San Raffaele University, School of Medicine, Via Olgettina 58, 20132, Milano, Italy. Electronic address: poli.guido@hsr.it.
authors.forename: Guido
authors.initials: G
authors.lastname: Poli
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002584:Cervix Uteri / Q000276:immunology / Q000821:virology*; D004261:DNA Replication / Q000187:drug effects; D004717:Endometrium / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D019259:Lamivudine; D037181:Lectins, C-Type / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D019713:Receptors, CCR5 / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*; D000099192:CD69 Antigens
chemical_list: D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D006684:HLA-DR Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D019259:Lamivudine; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D010626:Phenylethyl Alcohol; D019713:Receptors, CCR5; D000099192:CD69 Antigens; C584933:CCR5 protein, human; C508017:IL2RA protein, human; C005975:3,4-dihydroxyphenylethanol; C498154:CD38 protein, human
keywords: 5-Hydroxytyrosol; CD38; Endometrium-associated leukocytes; HIV-1; Human cervical tissue explants; Microbicide