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.
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.
复制标题
DOI：
10.3390/v13102043
复制
发表时间：
2021-10-11
期刊：
影响因子：
--
通讯作者：
Tugizov SM
中科院分区：
文献类型：
--
作者：
Herrera R;Rosbe K;Tugizov SM
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.
登录
查看更多内容
影响因子：
--
作者：
Henriques, Sonia Troeira;Quintas, Alexandre;Castanho, Miguel A. R. B.
通讯作者：
Castanho, Miguel A. R. B.
影响因子：
4.6
作者：
Cai, SR;Xu, G;McLeod, HL
通讯作者：
McLeod, HL
影响因子：
15.9
作者：
GANZ, T;SELSTED, ME;LEHRER, RI
通讯作者：
LEHRER, RI
影响因子：
12.4
作者：
Cashman, SM;Sadowski, SL;Kumar-Singh, R
通讯作者：
Kumar-Singh, R
影响因子：
3.4
作者：
Guterstam, Peter;Madani, Fatemeh;Langel, Ulo
通讯作者：
Langel, Ulo