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中国一种新型蝙蝠正呼肠孤病毒的分离及其与人类暴露的证据。

Isolation of a Novel Bat Rhabdovirus with Evidence of Human Exposure in China.

机构信息

National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.

Key Laboratory for Medical Virology and Viral Diseases, National Health Commission of the People's Republic of China, Beijing, China.

出版信息

mBio. 2021 Feb 22;13(1):e0287521. doi: 10.1128/mbio.02875-21. Epub 2022 Feb 15.

DOI:10.1128/mbio.02875-21
PMID:35164557
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8844929/
Abstract

Bats are well-recognized reservoirs of zoonotic viruses. Several spillover events from bats to humans have been reported, causing severe epidemic or endemic diseases including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), SARS-CoV, Middle East respiratory syndrome-CoV (MERS-CoV), henipaviruses, and filoviruses. In this study, a novel rhabdovirus species, provisionally named Rhinolophus rhabdovirus DPuer (DPRV), was identified from the horseshoe bat (Rhinolophus affinis) in Yunnan province, China, using next-generation sequencing. DPRV shedding in the spleen, liver, lung, and intestinal contents of wild bats with high viral loads was detected by real-time quantitative PCR, indicating that DPRV has tropism for multiple host tissues. Furthermore, DPRV can replicate in multiple mammalian cell lines, including BHK-21, A549, and MA104 cells, with the highest efficiency in hamster kidney cell line BHK-21, suggesting infectivity of DPRV in these cell line-derived hosts. Ultrastructure analysis revealed a characteristic bullet-shaped morphology and tightly clustered distribution of DPRV particles in the intracellular space. DPRV replicated efficiently in suckling mouse brains and caused death of suckling mice; death rates increased with passaging of DPRV in suckling mice. Moreover, 421 serum samples were collected from individuals who lived near the bat collection site and had fever symptoms within 1 year. DPRV-specific antibodies were detected in 20 (4.75%) human serum samples by indirect immunofluorescence assay. Furthermore, 10 (2.38%) serum samples were DPRV positive according to plaque reduction neutralization assay, which revealed potential transmission of DPRV from bats to humans and highlighted the potential public health risk. Potential vector association with DPRV was not found with negative viral RNA in bloodsucking arthropods. We identified a novel rhabdovirus from the horseshoe bat () in China with probable infectivity in humans. DPRV was isolated from several mammalian cell lines, indicating wide host tropism, excluding bats, of DPRV. DPRV replicated in the brains of suckling mice, and the death rate of suckling mice increased with passaging of DPRV . Serological tests indicated the possible infectivity of DPRV in humans and the potential transmission to humans. The present findings provide preliminary evidence for the potential risk of DPRV to public health. Additional studies with active surveillance are needed to address interspecies transmission and determine the pathogenicity of DPRV in humans.

摘要

蝙蝠是众所周知的人畜共患病病毒的宿主。已有数起因蝙蝠向人类溢出而导致的严重传染病或地方病的报告,包括严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)、严重急性呼吸系统综合征冠状病毒(SARS-CoV)、中东呼吸系统综合征冠状病毒(MERS-CoV)、亨德拉病毒和埃博拉病毒。在本研究中,使用下一代测序技术,从中国云南省的马蹄蝠(Rhinolophus affinis)中鉴定出一种新型弹状病毒物种,暂命名为菊头蝠弹状病毒大理株(DPRV)。通过实时定量 PCR 检测到具有高病毒载量的野生蝙蝠脾脏、肝脏、肺和肠内容物中 DPRV 的脱落,表明 DPRV 对多种宿主组织具有亲嗜性。此外,DPRV 可以在多种哺乳动物细胞系中复制,包括 BHK-21、A549 和 MA104 细胞系,在仓鼠肾细胞系 BHK-21 中效率最高,表明 DPRV 在这些细胞系来源的宿主中有感染性。超微结构分析显示 DPRV 颗粒在细胞内空间呈特征性的子弹形形态和紧密聚集分布。DPRV 在乳鼠脑中高效复制,并导致乳鼠死亡;随着 DPRV 在乳鼠中的传代,死亡率增加。此外,从蝙蝠采集地附近居住且在 1 年内有发热症状的 421 个人收集了血清样本。间接免疫荧光法检测到 20 份(4.75%)人血清样本中存在 DPRV 特异性抗体。此外,根据蚀斑减少中和试验,10 份(2.38%)血清样本为 DPRV 阳性,表明 DPRV 可能从蝙蝠传播给人类,并突出了潜在的公共卫生风险。在吸血节肢动物的血液中未发现与 DPRV 相关的潜在载体,因此未发现 DPRV 的潜在载体。我们从中国马蹄蝠中鉴定出一种新型的弹状病毒,其对人类可能具有传染性。DPRV 从几种哺乳动物细胞系中分离出来,表明 DPRV 除了蝙蝠以外,还广泛宿主亲和。DPRV 在乳鼠脑中复制,随着 DPRV 的传代,乳鼠的死亡率增加。血清学检测表明 DPRV 可能在人类中具有感染性,并可能传播给人类。这些发现为 DPRV 对公共卫生的潜在风险提供了初步证据。需要进行主动监测的进一步研究,以解决种间传播问题,并确定 DPRV 在人类中的致病性。

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