Evolution of Mayaro virus and its impact on transmission by urban vectors

摘要 马亚罗病毒（MAYV）是引起南美洲甲型病毒性发热疾病的第二大原因 国家近年来，MAYV获得了极大的关注，因为它的地理分布是 从南美洲和中美洲向北扩展到加勒比群岛。虽然散发的MAYV病例 尽管过去几年中报告了大量的MAYV疫情，但仍不清楚为什么现在大部分MAYV疫情都被 在拉丁美洲更常见，是什么因素导致了病毒的扩张， 新的地理区域。最近，生态流行病学调查证实， 在巴西感染了埃及伊蚊这就提出了一种可能性，即MAYV的适应性更好地传播， 城市病媒是导致这种病原体出现和扩散的主要因素。因此，研究 我们迫切需要评估这种可能性。 鉴于MAYV扩展到新的地理区域以及支持城市传播的证据， 我们对分离的埃及伊蚊、白纹伊蚊和MAYV菌株进行了媒介能力研究 在秘鲁的MAYV低（2002年）或高（2011年）传播年份。我们观察到分离到的MAYV毒株 在2011年爆发期间，两种伊蚊的感染、传播和传播频率更高， 埃及伊蚊和白纹伊蚊，而在2002年分离的菌株中检测到的传播微乎其微， 一年的低MAYV传输。在这项建议的研究中，我们假设MAYV正在适应 埃及伊蚊和白纹伊蚊更好地传播，E2糖蛋白 MAYV基因组的突变促进了这些蚊子载体中增强的感染性。我们将：1）检查向量 在秘鲁，使用易感动物模型，研究城市媒介对传播的MAYV毒株的感染能力; 2） 进行遗传研究，以评估E2糖蛋白突变及其对载体能力的贡献。 这项研究的完成将为我们理解MAYV传播提供关键知识， 鉴定和实验验证与增强传播相关的病毒基因。也会产生 研究MAYV其他方面的强大工具，包括反向遗传系统的开发 感染因此，这个项目代表着我们朝着了解的长期目标迈出的重要一步 MAYV的出现机制。

Abstract Mayaro virus (MAYV) is the second leading cause of alphavirus-induced febrile illness in South American countries. In recent years, MAYV has gained significant attention because its geographic distribution is expanding north from South and Central America into the Caribbean Islands. While sporadic cases of MAYV were reported in past years, it is still unclear why MAYV outbreaks of considerable proportion are now being recognized more frequently in Latin America and what factors are accounting for the expansion of the virus to new geographic areas. Recently, eco-epidemiological investigations have confirmed the presence of naturally infected Aedes aegypti in Brazil. This raises the possibility that adaptation of MAYV to be better transmitted by urban vectors is a major contributing factor to the emergence and expansion of this pathogen. Thus, studies are urgently needed to assess this possibility. Given the expansion of MAYV into new geographic areas and the evidence supporting urban transmission, we conducted vector competence studies with Aedes aegypti and Aedes albopictus and MAYV strains isolated during years of low (2002) or high MAYV transmission (2011) in Peru. We observed that a MAYV strain isolated during an outbreak in 2011 had greater frequency of infection, dissemination, and transmission in both Aedes aegypti and Aedes albopictus, whereas minimal to no transmission was detected with the strain isolated in 2002, a year of low MAYV transmission. In the studies of this proposal, we hypothesize that MAYV is adapting to be better transmitted by Aedes aegypti and Aedes albopictus and that evolutionary changes in the E2 glycoprotein of the MAYV genome promote enhanced infectivity in these mosquito vectors. We will: 1) examine the vector competence of urban vectors for circulating MAYV strains in Peru, using a susceptible animal model and 2) conduct genetic studies to assess E2 glycoprotein mutations and their contribution to vector competence. Completion of this study will provide critical knowledge to our understanding of MAYV transmission and will identify and experimentally validate viral genes associated with enhanced transmission. It will also generate powerful tools, including the development of reverse genetic systems, for studying other aspects of MAYV infection. Therefore, this project represents an important step towards our long-term objective of understanding the emergence mechanism of MAYV.