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三种马亚罗病毒基因型在食蟹猴中的比较发病机制。

Comparative pathogenesis of three Mayaro virus genotypes in the cynomolgus macaque.

机构信息

BIOQUAL Inc., Rockville, MD, 20852, USA.

Department of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA.

出版信息

J Gen Virol. 2024 Jul;105(7). doi: 10.1099/jgv.0.002001.

DOI:10.1099/jgv.0.002001
PMID:38995674
Abstract

Mayaro virus (MAYV), a mosquito-borne alphavirus, is considered an emerging threat to public health with epidemic potential. Phylogenetic studies show the existence of three MAYV genotypes. In this study, we provide a preliminary analysis of the pathogenesis of all three MAYV genotypes in cynomolgus macaques (, Mauritian origin). Significant MAYV-specific RNAemia and viremia were detected during acute infection in animals challenged intravenously with the three MAYV genotypes, and strong neutralizing antibody responses were observed. MAYV RNA was detected at high levels in lymphoid tissues, joint muscle and synovia over 1 month after infection, suggesting that this model could serve as a promising tool in studying MAYV-induced chronic arthralgia, which can persist for years. Significant leucopenia was observed across all MAYV genotypes, peaking with RNAemia. Notable differences in the severity of acute RNAemia and composition of cytokine responses were observed among the three MAYV genotypes. Our model showed no outward signs of clinical disease, but several major endpoints for future MAYV pathology and intervention studies are described. Disruptions to normal blood cell counts and cytokine responses were markedly distinct from those observed in macaque models of CHIKV infection, underlining the importance of developing non-human primate models specific to MAYV infection.

摘要

马亚罗病毒(MAYV)是一种蚊媒传播的甲病毒,被认为是对公共卫生具有潜在流行威胁的新兴威胁。系统发育研究表明存在三种 MAYV 基因型。在这项研究中,我们初步分析了三种 MAYV 基因型在食蟹猴(毛里求斯起源)中的发病机制。静脉内接种三种 MAYV 基因型的动物在急性感染期间均出现明显的 MAYV 特异性 RNA 血症和病毒血症,并观察到强烈的中和抗体反应。感染后 1 个月内,淋巴组织、关节肌肉和滑膜中均检测到高水平的 MAYV RNA,表明该模型可能成为研究 MAYV 诱导的慢性关节炎的有前途的工具,慢性关节炎可持续数年。所有 MAYV 基因型均观察到显著的白细胞减少症,与 RNA 血症峰值一致。三种 MAYV 基因型之间观察到急性 RNA 血症严重程度和细胞因子反应组成的显著差异。我们的模型没有表现出明显的临床疾病迹象,但描述了未来 MAYV 病理学和干预研究的几个主要终点。正常血细胞计数和细胞因子反应的紊乱与在感染 CHIKV 的猕猴模型中观察到的明显不同,这强调了开发针对 MAYV 感染的非人类灵长类动物模型的重要性。

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