5-Hydroxytyrosol inhibits HIV-1 replication in primary cells of the lower and upper female reproductive tract

Antiviral Res. 2017 Jun;142:16-20. doi: 10.1016/j.antiviral.2017.03.003. Epub 2017 Mar 7.

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-1BaL 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-1BaL replication 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.

Keywords: 5-Hydroxytyrosol; CD38; Endometrium-associated leukocytes; HIV-1; Human cervical tissue explants; Microbicide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD4 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Cervix Uteri / immunology
  • Cervix Uteri / virology*
  • DNA Replication / drug effects
  • Endometrium / virology
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV Infections / transmission
  • HIV-1 / drug effects*
  • HLA-DR Antigens / metabolism
  • Humans
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Lamivudine
  • Lectins, C-Type / metabolism
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / antagonists & inhibitors
  • Receptors, CCR5 / metabolism
  • Virus Replication / drug effects*

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CCR5 protein, human
  • CD4 Antigens
  • CD69 antigen
  • HLA-DR Antigens
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Membrane Glycoproteins
  • Receptors, CCR5
  • 3,4-dihydroxyphenylethanol
  • Lamivudine
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1
  • Phenylethyl Alcohol