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茹鲁阿察病毒分类学、对感染的耐受性和抗性以及小鼠模型中的炎症反应调节

Juruaça virus taxonomy, tolerance and resistance to infection, and inflammatory response modulation in murine model.

作者信息

da Silva Cabral Tatyane, Cayuela Natalie Chaves, Carvalho Karina Glazianne Barbosa, Pimenta Tamirys Simão, Rodrigues Ana Paula Drummond, Diniz Daniel Guerreiro, Quaresma Juarez Antônio Simões, de Almeida Medeiros Daniele Barbosa, Prazeres Ivy Tsuya Essashika, da Silva Sandro Patroca, Araújo Taís Pinheiro, da Costa Vasconcelos Pedro Fernando, Diniz Cristovam Wanderley Picanço, Diniz José Antonio Picanço

机构信息

Laboratório de Microscopia Eletrônica, Instituto Evandro Chagas, Avenida Almirante Barroso, 492, Bairro do Marco, CEP 66.093-020, Belém, Pará, Brasil.

Laboratório de Investigações em Neurodegeneração e Infecção, Universidade Federal do Pará, Instituto de Ciências Biológicas, Hospital Universitário João de Barros Barreto, Rua dos Mundurucus, 4487, Guamá, CEP: 66.073-005, Belém, Pará, Brasil.

出版信息

Npj Viruses. 2024 Oct 3;2(1):46. doi: 10.1038/s44298-024-00056-y.

DOI:10.1038/s44298-024-00056-y
PMID:40295833
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11721108/
Abstract

Juruaça virus (JUAV), previously unclassified, was isolated from bats and administered to neonatal and adult BALB/c mice to investigate acute and chronic disease progression. In this study, we conducted genomic sequencing to achieve taxonomic classification and utilized these models to explore the inflammatory response and sickness behavior in both neonatal and adult mice. Neonates received a single intranasal instillation of infected brain homogenate (20 µL), whereas 31-day-old mice were given the same volume intranasally for three consecutive days. Control groups were administered equal volumes of uninfected brain homogenate. Our findings reveal that intranasal JUAV infection-induced acute meningoencephalitis and death in neonates, while adult mice exhibited chronic infection with variable clinical signs, inflammatory mediator production, histopathological changes, and neuropathological features. Interestingly, only some adult mice showed sickness behavior post-infection, and among these, a subset continued to decline and die. The differential tissue damage observed in mice with and without overt disease symptoms suggests mechanisms of resistance or tolerance, where exceeding tolerance capacity resulted in pathological outcomes, including chronic dysfunction or death. This study provides the first evidence of JUAV's capability to infect mammals, demonstrating its distinct impact on bats and variable effects in neonatal and adult mice. We provisionally classified JUAV as closely related to the clade containing tombus-like virus 6 found in mute swan feces. Our research highlights the importance of understanding viral-host interactions and the inflammatory responses that contribute to disease variability, offering insights into tolerance and resistance mechanisms based on inflammatory response modulation.

摘要

茹鲁阿察病毒(JUAV),此前未分类,从蝙蝠中分离出来,并接种给新生和成年BALB/c小鼠,以研究急性和慢性疾病进展。在本研究中,我们进行了基因组测序以实现分类学分类,并利用这些模型探索新生和成年小鼠的炎症反应和疾病行为。新生小鼠经鼻内单次滴注感染性脑匀浆(20 μL),而31日龄小鼠连续三天经鼻内给予相同体积的感染性脑匀浆。对照组给予等量的未感染脑匀浆。我们的研究结果表明,经鼻内感染JUAV可导致新生小鼠急性脑膜脑炎和死亡,而成年小鼠表现为慢性感染,伴有不同的临床症状、炎症介质产生、组织病理学变化和神经病理学特征。有趣的是,只有一些成年小鼠在感染后表现出疾病行为,其中一部分继续衰弱并死亡。在有和没有明显疾病症状的小鼠中观察到的不同组织损伤表明存在抵抗或耐受机制,即超过耐受能力会导致病理结果,包括慢性功能障碍或死亡。本研究首次证明了JUAV感染哺乳动物的能力,表明其对蝙蝠有独特影响,对新生和成年小鼠有不同作用。我们暂时将JUAV分类为与在疣鼻天鹅粪便中发现的包含类番茄病毒6的进化枝密切相关。我们的研究强调了理解病毒-宿主相互作用以及导致疾病变异性的炎症反应的重要性,为基于炎症反应调节的耐受和抵抗机制提供了见解。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/11721108/d1803ed7a8b9/44298_2024_56_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/11721108/6a2939a7f651/44298_2024_56_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/11721108/610976f9e25c/44298_2024_56_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/11721108/e2c90327012c/44298_2024_56_Fig10_HTML.jpg
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