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5-羟基酪醇抑制HIV-1在女性上、下生殖道原代细胞中的复制。

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

作者信息

Saba Elisa, Panina-Bordignon Paola, Pagani Isabel, Origoni Massimo, Candiani Massimo, Doglioni Claudio, Taccagni Gianluca, Ghezzi Silvia, Alcami José, Vicenzi Elisa, Poli Guido

机构信息

AIDS Immunopathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy.

Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy.

出版信息

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

DOI:10.1016/j.antiviral.2017.03.003
PMID:28286236
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-1 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 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 CD38CD8 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.

摘要

我们研究了候选杀微生物剂5-羟基酪醇（5-HT）在原发性人宫颈组织外植体（CTE）和子宫内膜相关白细胞（EAL）中的潜在抗HIV-1活性。CTE取自接受子宫切除术妇女的组织，将其暴露于实验室适应的HIV-1或原发性病毒分离株中，同时存在或不存在5-HT或作为对照的3TC/拉米夫定，然后根据培养上清液中HIV-1 p24 Gag抗原的产生情况监测12天。还通过逆转录酶（RT）活性在EAL中评估HIV-1复制情况。5-HT的最高无毒浓度（CTE和EAL分别为200和100μM）对两个原代细胞系统中的病毒复制均产生了显著抑制作用。就CD4、CCR5、CD25、CD69和HLA-DR表达而言，5-HT并未引起CD4和CD8 T细胞活化谱的显著改变，尽管它降低了CD38CD8 T细胞的百分比。因此，5-HT值得作为预防HIV-1传播或抑制其在女性生殖道中复制的潜在候选杀微生物剂加以考虑。

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