Mayaro virus (MAYV) is a mosquito-transmitted alphavirus that causes debilitating and persistent arthritogenic disease. While MAYV was previously reported to infect non-human primates (NHP), characterization of MAYV pathogenesis is currently lacking. Therefore, in this study we characterized MAYV infection and immunity in rhesus macaques. To inform the selection of a viral strain for NHP experiments, we evaluated five MAYV strains in C57BL/6 mice and showed that MAYV strain BeAr505411 induced robust tissue dissemination and disease. Three male rhesus macaques were subcutaneously challenged with 105 plaque-forming units of this strain into the arms. Peak plasma viremia occurred at 2 days post-infection (dpi). NHPs were taken to necropsy at 10 dpi to assess viral dissemination, which included the muscles and joints, lymphoid tissues, major organs, male reproductive tissues, as well as peripheral and central nervous system tissues. Histological examination demonstrated that MAYV infection was associated with appendicular joint and muscle inflammation as well as presence of perivascular inflammation in a wide variety of tissues. One animal developed a maculopapular rash and two NHP had viral RNA detected in upper torso skin samples, which was associated with the presence of perivascular and perifollicular lymphocytic aggregation. Analysis of longitudinal peripheral blood samples indicated a robust innate and adaptive immune activation, including the presence of anti-MAYV neutralizing antibodies with activity against related Una virus and chikungunya virus. Inflammatory cytokines and monocyte activation also peaked coincident with viremia, which was well supported by our transcriptomic analysis highlighting enrichment of interferon signaling and other antiviral processes at 2 days post MAYV infection. The rhesus macaque model of MAYV infection recapitulates many of the aspects of human infection and is poised to facilitate the evaluation of novel therapies and vaccines targeting this re-emerging virus.

中文翻译：

---

马亚罗病毒在恒河猴中的发病机制和免疫。

马亚罗病毒 (MAYV) 是一种由蚊子传播的甲病毒，会导致衰弱和持续性关节炎疾病。虽然先前报道 MAYV 会感染非人类灵长类动物 (NHP)，但目前缺乏 MAYV 发病机制的表征。因此，在这项研究中，我们对恒河猴的 MAYV 感染和免疫进行了表征。为了为 NHP 实验选择病毒株提供信息，我们在 C57BL/6 小鼠中评估了五种 MAYV 毒株，结果表明 MAYV 毒株 BeAr505411 诱导了强大的组织传播和疾病。三只雄性恒河猴的手臂上皮下注射了 105 个斑块形成单位的该品系。血浆病毒血症峰值出现在感染后 2 天 (dpi)。在 10 dpi 时将 NHP 进行尸检，以评估病毒传播情况，其中包括肌肉和关节、淋巴组织、主要器官、男性生殖组织以及周围和中枢神经系统组织。组织学检查表明，MAYV 感染与阑尾关节和肌肉炎症以及多种组织中血管周围炎症的存在有关。一只动物出现斑丘疹，两只 NHP 在上躯干皮肤样本中检测到病毒 RNA，这与血管周围和毛囊周围淋巴细胞聚集的存在有关。纵向外周血样本分析表明存在强大的先天性和适应性免疫激活，包括存在具有抗相关乌纳病毒和基孔肯雅病毒活性的抗 MAYV 中和抗体。炎症细胞因子和单核细胞活化也与病毒血症同时达到峰值，我们的转录组分析充分支持了这一点，该分析强调了 MAYV 感染后 2 天干扰素信号传导和其他抗病毒过程的富集。MAYV 感染的恒河猴模型概括了人类感染的许多方面，并有望促进针对这种重新出现的病毒的新疗法和疫苗的评估。