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

马亚罗病毒的进化及其对城市媒介传播的影响

• 批准号: 10753968
• 负责人: Patricia Veronica Aguilar
• 金额: $ 24万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-06 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10753968
• 关键词: Accounting; Aedes; Alphavirus; Animal Model; Area; Attention; Brazil; Central America; Chikungunya virus; Cities; Country; Culicidae; Dengue Virus; Development; Disease Outbreaks; Europe; Evolution; Fever; Frequencies; Genetic study; Geographic Distribution; Geographic Locations; Glycoproteins; Haiti; Health Policy; Human; Infection; Knowledge; Laboratory Study; Latin America; Maintenance; Mayaro virus; Modeling; Mus; Mutation; North America; Persons; Peru; Predisposition; Primates; Public Health; Reporting; Sequence Analysis; South America; South American; System; Testing; Travel; Vectorial capacity; Viral Genes; Viral Genome; Virus; Virus Diseases; West Indies; emerging pathogen; epidemiology study; evidence base; forest; genetic analysis; genome sequencing; nonsynonymous mutation; novel; pathogen; reverse genetics; surveillance study; tool; transmission process; vector; vector competence; vector mosquito; viral transmission; whole genome

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.

抽象的 Mayaro病毒（Mayv）是南美α诱导的高温疾病的第二大主要原因 国家。近年来，梅夫（Mayv）受到了极大的关注，因为其地理分布是 从南美洲和中美洲向北扩展到加勒比群岛。而零星的疾病 在过去的几年中报道了，目前尚不清楚为什么现在有相当比例的爆发 在拉丁美洲认识到更频繁的频率，以及哪些因素将病毒扩展到 新地理区域。最近，生态流行病学研究已经证实了自然存在 在巴西被感染的埃及埃及。这增加了Mayv改编更好地传播Mayv的可能性 城市媒介是导致该病原体出现和扩展的主要因素。因此，研究是 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， 我们通过伊蚊和艾德斯白化菌和Mayv菌株进行了矢量能力研究。 在低年度（2002年）或秘鲁的高贫民传输（2011年）中。我们观察到分离的Mayv菌株 在2011年的一次爆发中，两种艾德斯的感染，传播和传播的频率更高 埃及和艾德斯白化病，而在2002年分离的菌株中，检测到最小至未传播 一年的低MAYV传播。在该提案的研究中，我们假设Mayv正在适应 埃及埃及和艾德斯白化菌和E2糖蛋白的进化变化更好地传播 在这些蚊子载体中，Mayv基因组促进了增强的感染性。我们将：1）检查向量 使用易感动物模型和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对Mayv传播的理解提供关键知识，并将 识别和实验验证与增强传播相关的病毒基因。它也会生成 强大的工具，包括开发反向遗传系统，用于研究Mayv的其他方面 感染。因此，该项目是朝着我们理解的长期目标迈出的重要一步 Mayv的出现机制。