• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

人β防御素 2 和 3 融合 HIV-1 Tat 蛋白转导结构域对极化的婴儿扁桃体上皮细胞中 HIV-1 的灭活作用。

Inactivation of HIV-1 in Polarized Infant Tonsil Epithelial Cells by Human Beta-Defensins 2 and 3 Tagged with the Protein Transduction Domain of HIV-1 Tat.

机构信息

Department of Medicine, University of California-San Francisco, 513 Parnassus Ave., San Francisco, CA 94143, USA.

Department of Otolaryngology, University of California-San Francisco, San Francisco, CA 94115, USA.

出版信息

Viruses. 2021 Oct 11;13(10):2043. doi: 10.3390/v13102043.

DOI:10.3390/v13102043
PMID:34696473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8538026/
Abstract

Mother-to-child transmission (MTCT) of HIV-1 may occur during pregnancy, labor, and breastfeeding; however, the molecular mechanism of MTCT of virus remains poorly understood. Infant tonsil mucosal epithelium may sequester HIV-1, serving as a transient reservoir, and may play a critical role in MTCT. Innate immune proteins human beta-defensins 2 (hBD-2) and -3 may inactivate intravesicular virions. To establish delivery of hBD-2 and -3 into vesicles containing HIV-1, we tagged hBDs with the protein transduction domain (PTD) of HIV-1 Tat, which facilitates an efficient translocation of proteins across cell membranes. Our new findings showed that hBD-2 and -3 proteins tagged with PTD efficiently penetrated polarized tonsil epithelial cells by endocytosis and direct penetration. PTD-initiated internalization of hBD-2 and -3 proteins into epithelial cells led to their subsequent penetration of multivesicular bodies (MVB) and vacuoles containing HIV-1. Furthermore, PTD played a role in the fusion of vesicles containing HIV-1 with lysosomes, where virus was inactivated. PTD-initiated internalization of hBD-2 and -3 proteins into ex vivo tonsil tissue explants reduced the spread of virus from epithelial cells to CD4+ T lymphocytes, CD68+ macrophages, and CD1c+ dendritic cells, suggesting that this approach may serve as an antiviral strategy for inactivating intraepithelial HIV-1 and reducing viral MTCT.

摘要

母婴传播 (MTCT) 的 HIV-1 可能发生在怀孕、分娩和母乳喂养期间;然而，病毒 MTCT 的分子机制仍知之甚少。婴儿扁桃体黏膜上皮细胞可能会隔离 HIV-1，作为一个短暂的储库，并可能在 MTCT 中发挥关键作用。先天免疫蛋白人β防御素 2 (hBD-2) 和 -3 可能使囊泡内的病毒失活。为了建立 hBD-2 和 -3 递送到含有 HIV-1 的囊泡中，我们用 HIV-1 Tat 的蛋白转导结构域 (PTD) 标记 hBDs，这促进了蛋白质穿过细胞膜的有效转运。我们的新发现表明，带有 PTD 的 hBD-2 和 -3 蛋白通过内吞作用和直接穿透有效地穿透极化的扁桃体上皮细胞。PTD 引发的 hBD-2 和 -3 蛋白内化进入上皮细胞，导致它们随后穿透含有 HIV-1 的多泡体 (MVB) 和空泡。此外，PTD 在含有 HIV-1 的囊泡与溶酶体融合中发挥作用，在溶酶体中病毒被失活。PTD 引发的 hBD-2 和 -3 蛋白内吞进入离体扁桃体组织外植体，减少了病毒从上皮细胞向 CD4+T 淋巴细胞、CD68+巨噬细胞和 CD1c+树突状细胞的传播，这表明这种方法可能作为一种抗病毒策略，用于灭活上皮内 HIV-1 并减少病毒的母婴传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/2f742845b245/viruses-13-02043-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/ca668824f813/viruses-13-02043-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/9d60a9ada56a/viruses-13-02043-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/74599764e60b/viruses-13-02043-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/b6dd9d93f7f5/viruses-13-02043-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/d4877e0d21cf/viruses-13-02043-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/08b658cc4a9c/viruses-13-02043-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/3af13d863ef8/viruses-13-02043-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/e1cfb4a30ab1/viruses-13-02043-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/f001653cb7f5/viruses-13-02043-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/3bca6edd17d2/viruses-13-02043-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/e299919ef5df/viruses-13-02043-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/2f742845b245/viruses-13-02043-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/ca668824f813/viruses-13-02043-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/9d60a9ada56a/viruses-13-02043-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/74599764e60b/viruses-13-02043-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/b6dd9d93f7f5/viruses-13-02043-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/d4877e0d21cf/viruses-13-02043-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/08b658cc4a9c/viruses-13-02043-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/3af13d863ef8/viruses-13-02043-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/e1cfb4a30ab1/viruses-13-02043-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/f001653cb7f5/viruses-13-02043-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/3bca6edd17d2/viruses-13-02043-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/e299919ef5df/viruses-13-02043-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96fa/8538026/2f742845b245/viruses-13-02043-g012.jpg

相似文献

1
Inactivation of HIV-1 in Polarized Infant Tonsil Epithelial Cells by Human Beta-Defensins 2 and 3 Tagged with the Protein Transduction Domain of HIV-1 Tat.人β防御素 2 和 3 融合 HIV-1 Tat 蛋白转导结构域对极化的婴儿扁桃体上皮细胞中 HIV-1 的灭活作用。
Viruses. 2021 Oct 11;13(10):2043. doi: 10.3390/v13102043.
2
Human Immunodeficiency Virus (HIV) and Human Cytomegalovirus (HCMV) Coinfection of Infant Tonsil Epithelium May Synergistically Promote both HIV-1 and HCMV Spread and Infection.人类免疫缺陷病毒 (HIV) 和人类巨细胞病毒 (HCMV) 对婴儿扁桃体上皮细胞的合并感染可能协同促进 HIV-1 和 HCMV 的传播和感染。
J Virol. 2021 Aug 25;95(18):e0092121. doi: 10.1128/JVI.00921-21.
3
Release of HIV-1 sequestered in the vesicles of oral and genital mucosal epithelial cells by epithelial-lymphocyte interaction.通过上皮细胞与淋巴细胞的相互作用，释放存在于口腔和生殖器黏膜上皮细胞囊泡中的HIV-1。
PLoS Pathog. 2017 Feb 27;13(2):e1006247. doi: 10.1371/journal.ppat.1006247. eCollection 2017 Feb.
4
Human beta-defensins 2 and -3 cointernalize with human immunodeficiency virus via heparan sulfate proteoglycans and reduce infectivity of intracellular virions in tonsil epithelial cells.人β-防御素2和-3通过硫酸乙酰肝素蛋白聚糖与人免疫缺陷病毒共同内化，并降低扁桃体上皮细胞内病毒粒子的感染性。
Virology. 2016 Jan;487:172-87. doi: 10.1016/j.virol.2015.09.025. Epub 2015 Nov 2.
5
HIV internalization into oral and genital epithelial cells by endocytosis and macropinocytosis leads to viral sequestration in the vesicles.HIV 通过胞吞作用和巨胞饮作用内化到口腔和生殖器上皮细胞中，导致病毒被隔离在囊泡中。
Virology. 2018 Feb;515:92-107. doi: 10.1016/j.virol.2017.12.012. Epub 2017 Dec 22.
6
Extracellular HIV-1 Tat induces human beta-defensin-2 production via NF-kappaB/AP-1 dependent pathways in human B cells.细胞外 HIV-1 Tat 通过 NF-κB/AP-1 依赖途径诱导人 B 细胞人β防御素-2 的产生。
Mol Cells. 2012 Apr;33(4):335-41. doi: 10.1007/s10059-012-2287-0. Epub 2012 Mar 23.
7
HIV-1 proteins gp120 and tat induce the epithelial-mesenchymal transition in oral and genital mucosal epithelial cells.HIV-1 蛋白 gp120 和 tat 诱导口腔和生殖器黏膜上皮细胞发生上皮-间充质转化。
PLoS One. 2019 Dec 23;14(12):e0226343. doi: 10.1371/journal.pone.0226343. eCollection 2019.
8
Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication.人上皮β-防御素2和3可抑制HIV-1复制。
AIDS. 2003 Nov 7;17(16):F39-48. doi: 10.1097/00002030-200311070-00001.
9
A model system of oral HIV exposure, using human palatine tonsil, reveals extensive binding of HIV infectivity, with limited progression to primary infection.一个使用人类腭扁桃体的口腔HIV暴露模型系统显示，HIV感染力有广泛结合，但进展至原发性感染的情况有限。
J Infect Dis. 2004 Dec 1;190(11):1989-97. doi: 10.1086/425423. Epub 2004 Nov 3.
10
Role of human beta-defensins in HIV infection.人β-防御素在HIV感染中的作用。
Adv Dent Res. 2006 Apr 1;19(1):42-8. doi: 10.1177/154407370601900109.

引用本文的文献

1
Advances in the Role of Antimicrobial Peptides in the Management of Sexually Transmitted Infections.抗菌肽在性传播感染管理中的作用进展
J Clin Lab Anal. 2025 Jun;39(11):e70041. doi: 10.1002/jcla.70041. Epub 2025 May 14.
2
Molecular Pathogenesis of Human Immunodeficiency Virus-Associated Disease of Oropharyngeal Mucosal Epithelium.人类免疫缺陷病毒相关口咽黏膜上皮疾病的分子发病机制
Biomedicines. 2023 May 14;11(5):1444. doi: 10.3390/biomedicines11051444.

本文引用的文献

1
Human Beta-Defensin 2 and 3 Inhibit HIV-1 Replication in Macrophages.人β-防御素 2 和 3 抑制巨噬细胞中的 HIV-1 复制。
Front Cell Infect Microbiol. 2021 Jul 1;11:535352. doi: 10.3389/fcimb.2021.535352. eCollection 2021.
2
Human Immunodeficiency Virus (HIV) and Human Cytomegalovirus (HCMV) Coinfection of Infant Tonsil Epithelium May Synergistically Promote both HIV-1 and HCMV Spread and Infection.人类免疫缺陷病毒 (HIV) 和人类巨细胞病毒 (HCMV) 对婴儿扁桃体上皮细胞的合并感染可能协同促进 HIV-1 和 HCMV 的传播和感染。
J Virol. 2021 Aug 25;95(18):e0092121. doi: 10.1128/JVI.00921-21.
3
Vaginal Epithelium Transiently Harbours HIV-1 Facilitating Transmission.
阴道上皮细胞短暂携带 HIV-1 促进传播。
Front Cell Infect Microbiol. 2021 Mar 17;11:634647. doi: 10.3389/fcimb.2021.634647. eCollection 2021.
4
Exploring novel and potent cell penetrating peptides in the proteome of SARS-COV-2 using bioinformatics approaches.利用生物信息学方法探索 SARS-CoV-2 蛋白质组中的新型有效穿透细胞肽。
PLoS One. 2021 Feb 19;16(2):e0247396. doi: 10.1371/journal.pone.0247396. eCollection 2021.
5
Anion hopping of (and on) functional oligoarginines: from chloroform to cells.功能性寡聚精氨酸的（及在其上的）阴离子跳跃：从氯仿到细胞
Soft Matter. 2006 Jul 20;2(8):636-641. doi: 10.1039/b606955j.
6
Internalization mechanisms of cell-penetrating peptides.细胞穿透肽的内化机制
Beilstein J Nanotechnol. 2020 Jan 9;11:101-123. doi: 10.3762/bjnano.11.10. eCollection 2020.
7
Cell penetrating peptides: the potent multi-cargo intracellular carriers.细胞穿透肽：强大的多功能细胞内载体。
Expert Opin Drug Deliv. 2019 Nov;16(11):1227-1258. doi: 10.1080/17425247.2019.1676720. Epub 2019 Oct 15.
8
Cell-penetrating peptide sequence and modification dependent uptake and subcellular distribution of green florescent protein in different cell lines.穿膜肽序列和修饰依赖性对不同细胞系中绿色荧光蛋白的摄取和亚细胞分布。
Sci Rep. 2019 Apr 18;9(1):6298. doi: 10.1038/s41598-019-42456-8.
9
Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore.富含精氨酸的细胞穿透肽诱导形成多层膜，随后通过融合孔进入细胞。
Proc Natl Acad Sci U S A. 2018 Nov 20;115(47):11923-11928. doi: 10.1073/pnas.1811520115. Epub 2018 Nov 5.
10
Cell-Penetrating Peptide Mediates Intracellular Membrane Passage of Human Papillomavirus L2 Protein to Trigger Retrograde Trafficking.穿膜肽介导人乳头瘤病毒 L2 蛋白穿越细胞内膜引发逆行转运。
Cell. 2018 Sep 6;174(6):1465-1476.e13. doi: 10.1016/j.cell.2018.07.031. Epub 2018 Aug 16.