Immunocompetent mouse models revealed that S100A4+ monocytes/macrophages facilitate long-term Zika virus infection in the testes.

IF 8.4 2区 医学 Q1 IMMUNOLOGY
Emerging Microbes & Infections Pub Date : 2024-12-01 Epub Date: 2024-01-07 DOI:10.1080/22221751.2023.2300466
Wei Yang, Chen Zhang, Li-Bo Liu, Zhan-Zhan Bian, Jia-Tong Chang, Dong-Ying Fan, Na Gao, Pei-Gang Wang, Jing An
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引用次数: 0

Abstract

During its global epidemic, Zika virus (ZIKV) attracted widespread attention due to its link with various severe neurological symptoms and potential harm to male fertility. However, the understanding of how ZIKV invades and persists in the male reproductive system is limited due to the lack of immunocompetent small animal models. In this study, immunocompetent murine models were generated by using anti-IFNAR antibody blocked C57BL/6 male mice and human STAT2 (hSTAT2) knock in (KI) male mice. After infection, viral RNA could persist in the testes even after the disappearance of viremia. We also found a population of ZIKV-susceptible S100A4+ monocytes/macrophages that were recruited into testes from peripheral blood and played a crucial role for ZIKV infection in the testis. By using single-cell RNA sequencing, we also proved that S100A4+ monocytes/macrophages had a great impact on the microenvironment of ZIKV-infected testes, thus promoting ZIKV-induced testicular lesions. In conclusion, this study proposed a novel mechanism of long-term ZIKV infection in the male reproductive system.

免疫功能正常的小鼠模型显示,S100A4+单核细胞/巨噬细胞有助于寨卡病毒在睾丸内的长期感染。
寨卡病毒(ZIKV)在全球流行期间,因其与各种严重的神经症状和对男性生育能力的潜在危害有关而引起广泛关注。然而,由于缺乏免疫功能健全的小动物模型,人们对 ZIKV 如何侵入并在男性生殖系统中存活的了解十分有限。在本研究中,通过使用抗IFNAR抗体阻断的C57BL/6雄性小鼠和人STAT2(hSTAT2)基因敲入(KI)雄性小鼠,建立了免疫功能正常的小鼠模型。感染后,即使病毒血症消失,病毒 RNA 仍可在睾丸中存活。我们还发现了ZIKV易感的S100A4+单核细胞/巨噬细胞群,它们从外周血中被招募到睾丸中,并在睾丸的ZIKV感染中发挥着关键作用。通过单细胞 RNA 测序,我们还证明了 S100A4+ 单核细胞/巨噬细胞对 ZIKV 感染睾丸的微环境有很大影响,从而促进了 ZIKV 诱导的睾丸病变。总之,本研究提出了ZIKV长期感染男性生殖系统的新机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Emerging Microbes & Infections
Emerging Microbes & Infections IMMUNOLOGY-MICROBIOLOGY
CiteScore
26.20
自引率
2.30%
发文量
276
审稿时长
20 weeks
期刊介绍: Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses. The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries. This journal addresses topics of critical biological and clinical importance, including but not limited to: - Epidemic surveillance - Clinical manifestations - Diagnosis and management - Cellular and molecular pathogenesis - Innate and acquired immune responses between emerging microbes and their hosts - Drug discovery - Vaccine development research Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.
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