用于研究黏膜HIV-1传播与预防的CD34T+人源化小鼠模型

CD34T+ Humanized Mouse Model to Study Mucosal HIV-1 Transmission and Prevention.

作者信息

Vanshylla Kanika, Held Kathrin, Eser Tabea M, Gruell Henning, Kleipass Franziska, Stumpf Ricarda, Jain Kanika, Weiland Daniela, Münch Jan, Grüttner Berthold, Geldmacher Christof, Klein Florian

机构信息

Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.

Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU, 80802 Munich, Germany.

出版信息

Vaccines (Basel). 2021 Feb 27;9(3):198. doi: 10.3390/vaccines9030198.

DOI:10.3390/vaccines9030198

PMID:33673566

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7997265/

Abstract

Humanized mice are critical for HIV-1 research, but humanized mice generated from cord blood are inefficient at mucosal HIV-1 transmission. Most mucosal HIV-1 transmission studies in mice require fetal tissue-engraftment, the use of which is highly restricted or prohibited. We present a fetal tissue-independent model called CD34T+ with enhanced human leukocyte levels in the blood and improved T cell homing to the gut-associated lymphoid tissue. CD34T+ mice are highly permissive to intra-rectal HIV-1 infection and also show normal diversification in vivo despite high viral replication. Moreover, mucosal infection in CD34T+ mice can be prevented by infusion of broadly neutralizing antibodies. CD34T+ mice can be rapidly and easily generated using only cord blood cells and do not require any complicated surgical procedures for the humanization process. Therefore, CD34T+ mice provide a novel platform for mucosal HIV-1 transmission studies as well as rapid in vivo testing of novel prevention molecules against HIV-1.

摘要

人源化小鼠对HIV-1研究至关重要，但由脐带血产生的人源化小鼠在黏膜HIV-1传播方面效率低下。小鼠中大多数黏膜HIV-1传播研究需要植入胎儿组织，而胎儿组织的使用受到严格限制或禁止。我们提出了一种不依赖胎儿组织的模型，称为CD34T+，其血液中的人类白细胞水平有所提高，且T细胞归巢至肠道相关淋巴组织的能力得到改善。CD34T+小鼠对直肠内HIV-1感染高度敏感，尽管病毒复制水平很高，但在体内也表现出正常的多样化。此外，通过输注广泛中和抗体可以预防CD34T+小鼠的黏膜感染。仅使用脐带血细胞就能快速、轻松地生成CD34T+小鼠，并且在人源化过程中不需要任何复杂的外科手术。因此，CD34T+小鼠为黏膜HIV-1传播研究以及针对HIV-1的新型预防分子的快速体内测试提供了一个新平台。