PMID- 28286236 OWN - NLM STAT- MEDLINE DCOM- 20171215 LR - 20180213 IS - 1872-9096 (Electronic) IS - 0166-3542 (Linking) VI - 142 DP - 2017 Jun TI - 5-Hydroxytyrosol inhibits HIV-1 replication in primary cells of the lower and upper female reproductive tract. PG - 16-20 LID - S0166-3542(16)30499-5 [pii] LID - 10.1016/j.antiviral.2017.03.003 [doi] AB - 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-1(BaL) or 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-1(BaL) replication was also evaluated in EAL by reverse transcriptase (RT) activity. The highest nontoxic concentrations of 5-HT (200 and 100 muM 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. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Saba, Elisa AU - Saba E AD - 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. FAU - Panina-Bordignon, Paola AU - Panina-Bordignon P AD - 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. FAU - Pagani, Isabel AU - Pagani I AD - 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. FAU - Origoni, Massimo AU - Origoni M AD - 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. FAU - Candiani, Massimo AU - Candiani M AD - 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. FAU - Doglioni, Claudio AU - Doglioni C AD - 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. FAU - Taccagni, Gianluca AU - Taccagni G AD - Pathology Unit, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy. Electronic address: taccagni.gianluca@hsr.it. FAU - Ghezzi, Silvia AU - Ghezzi S AD - 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. FAU - Alcami, Jose AU - Alcami J AD - 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. FAU - Vicenzi, Elisa AU - Vicenzi E AD - 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. FAU - Poli, Guido AU - Poli G AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170307 PL - Netherlands TA - Antiviral Res JT - Antiviral research JID - 8109699 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, T-Lymphocyte) RN - 0 (CCR5 protein, human) RN - 0 (CD4 Antigens) RN - 0 (CD69 antigen) RN - 0 (HLA-DR Antigens) RN - 0 (IL2RA protein, human) RN - 0 (Interleukin-2 Receptor alpha Subunit) RN - 0 (Lectins, C-Type) RN - 0 (Membrane Glycoproteins) RN - 0 (Receptors, CCR5) RN - 10597-60-1 (3,4-dihydroxyphenylethanol) RN - 2T8Q726O95 (Lamivudine) RN - EC 3.2.2.5 (CD38 protein, human) RN - EC 3.2.2.6 (ADP-ribosyl Cyclase 1) RN - ML9LGA7468 (Phenylethyl Alcohol) SB - IM MH - ADP-ribosyl Cyclase 1/metabolism MH - Adult MH - Aged MH - Antigens, CD/metabolism MH - Antigens, Differentiation, T-Lymphocyte/metabolism MH - CD4 Antigens/metabolism MH - CD4-Positive T-Lymphocytes/metabolism MH - CD8-Positive T-Lymphocytes/metabolism MH - Cervix Uteri/immunology/*virology MH - DNA Replication/drug effects MH - Endometrium/virology MH - Female MH - HIV Infections/*drug therapy/immunology/prevention & control/transmission MH - HIV-1/*drug effects MH - HLA-DR Antigens/metabolism MH - Humans MH - Interleukin-2 Receptor alpha Subunit/metabolism MH - Lamivudine MH - Lectins, C-Type/metabolism MH - Membrane Glycoproteins/metabolism MH - Middle Aged MH - Phenylethyl Alcohol/*analogs & derivatives/antagonists & inhibitors MH - Receptors, CCR5/metabolism MH - Virus Replication/*drug effects OTO - NOTNLM OT - 5-Hydroxytyrosol OT - CD38 OT - Endometrium-associated leukocytes OT - HIV-1 OT - Human cervical tissue explants OT - Microbicide EDAT- 2017/03/14 06:00 MHDA- 2017/12/16 06:00 CRDT- 2017/03/14 06:00 PHST- 2016/09/06 00:00 [received] PHST- 2017/02/27 00:00 [revised] PHST- 2017/03/01 00:00 [accepted] PHST- 2017/03/14 06:00 [pubmed] PHST- 2017/12/16 06:00 [medline] PHST- 2017/03/14 06:00 [entrez] AID - S0166-3542(16)30499-5 [pii] AID - 10.1016/j.antiviral.2017.03.003 [doi] PST - ppublish SO - Antiviral Res. 2017 Jun;142:16-20. doi: 10.1016/j.antiviral.2017.03.003. Epub 2017 Mar 7.