Patel Aum R, Dulcey Melissa, Abid Nabil, Cash Melanie N, Dailey Jordan, Salemi Marco, Mavian Carla, Vittor Amy Y
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA.
Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA.
Acta Trop. 2023 Jun;242:106894. doi: 10.1016/j.actatropica.2023.106894. Epub 2023 Mar 23.
Mayaro virus (MAYV) is an emergent arthropod-borne virus that causes an acute febrile illness accompanied by arthralgia, similar to chikungunya virus. Increasing urbanization of MAYV outbreaks in the Americas has led to concerns for geographic expansion and spillover. Given the potential importance of this pathogen, we sought to fill critical gaps in knowledge regarding MAYV infectivity and geographic variation. This study describes the cytopathogenicity of MAYV in human dermal fibroblasts, human skeletal muscle satellite cells, human embryonic kidney cells (HEK), peripherally derived human macrophages, and Vero cells. We found that regional differences between these viruses do not affect replication kinetics, with high titers peaking at 37 h post infection. MAYV-U, did however, cause the most cytopathic effect in a time-dependent manner. Compared to the other two prototypic isolates, MAYV-U harbors unique mutations in the E2 protein, D60G and S205F, that are likely to interact with the host cell receptor and could affect infectivity. We further demonstrate that pre-treatment of cells with interferon-β inhibited viral replication in a dose-dependent manner. Together, these findings advance our understanding of MAYV infection of human target cells and provide initial data regarding variation according to geography.
马亚罗病毒(MAYV)是一种新出现的节肢动物传播病毒,可引起类似于基孔肯雅病毒的伴有关节痛的急性发热疾病。美洲地区马亚罗病毒疫情的城市化程度不断提高,引发了人们对其地理扩张和溢出效应的担忧。鉴于这种病原体的潜在重要性,我们试图填补关于马亚罗病毒感染性和地理变异的关键知识空白。本研究描述了马亚罗病毒在人皮肤成纤维细胞、人骨骼肌卫星细胞、人胚肾细胞(HEK)、外周血来源的人巨噬细胞和非洲绿猴肾细胞(Vero细胞)中的细胞致病性。我们发现这些病毒之间的区域差异不影响复制动力学,高滴度在感染后37小时达到峰值。然而,马亚罗病毒-U确实以时间依赖性方式引起了最明显的细胞病变效应。与其他两种原型毒株相比,马亚罗病毒-U在E2蛋白中存在独特的突变,即D60G和S205F,这些突变可能与宿主细胞受体相互作用并可能影响感染性。我们进一步证明,用干扰素-β预处理细胞以剂量依赖性方式抑制了病毒复制。这些发现共同推进了我们对马亚罗病毒感染人类靶细胞的理解,并提供了关于地理变异的初步数据。