Chikungunya Virus Exposure Partially Cross-Protects against Mayaro Virus Infection in Mice
Chikungunya Virus Exposure Partially Cross-Protects against Mayaro Virus Infection in Mice
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DOI：
10.1128/jvi.01122-21
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发表时间：
2021-12-01
影响因子：
5.4
通讯作者：
Moraes Figueiredo, Luiz Tadeu
中科院分区：
文献类型：
--
作者：
Fumagalli, Marcilio Jorge;de Souza, William Marciel;Moraes Figueiredo, Luiz Tadeu
基孔肯雅病毒(CHIKV)和马雅罗病毒(MAYV)是塞姆利基森林病毒抗原复合体中关系密切的成员，被归类为Togaviridae科甲型病毒属。这些病毒会导致人类疾病，伴随着突然发烧和关节炎症，可以持续很长一段时间。CHIKV是世界范围内大规模暴发的病原体，MAYV感染代表着拉丁美洲日益严重的公共卫生问题，导致零星病例和地理有限的暴发。考虑到CHIKV和MAYV之间的关系，本研究旨在评估现有的CHIKV免疫是否对MAYV感染具有保护作用。免疫活性C57BL/6小鼠经腹感染CHIKV，4周后在后爪感染MAYV。我们观察到，CHIKV免疫的存在赋予了对继发性MAYV感染的部分交叉保护，降低了疾病严重程度、组织病毒载量和组织病理学评分。有趣的是，来自人和鼠的CHIKV抗体对MAYV表现出较低的交叉中和能力，但在二次感染后中和活性显著增加。此外，耗尽获得性免疫细胞(CD4(+)T、CD8(+)T和CD19(+)B细胞)并没有改变交叉保护表型，这表明CHIKV刺激的不同细胞亚群或适应性免疫细胞组合对MAYV具有部分交叉保护作用。在继发感染MAYV的动物中，促炎症细胞因子，如干扰素-γ的减少，表明天然免疫在交叉保护中的作用。我们的发现揭示了先前存在的对致炎甲型病毒的免疫可能如何影响继发感染，继发感染可能进一步对疾病结局和病毒传播产生相关影响。基孔肯雅病毒主要存在于发展中国家，造成数百万人感染，而近亲马亚罗病毒仅限于加勒比和拉丁美洲的热带地区。马亚罗病毒的潜在出现和向其他高危地区的传播增加了科学界对迫在眉睫的全球流行病的关注。在这里，我们设计了一种基孔肯雅和马亚罗病毒感染小鼠的实验方案，它开发了一种可测量和可量化的疾病，使我们能够推断在二次病毒感染期间潜在的免疫效应。我们的结果表明，在继发的Mayaro感染期间，先前感染基孔肯雅病毒能够降低临床结局的严重性。我们提供了对密切相关病毒二次感染期间免疫学特征的科学了解，从而有助于更好地了解病毒传播和这些疾病的病理结果。
Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are closely related members of the Semliki Forest virus antigenic complex classified as belonging to the genus Alphavirus of the family Togaviridae. These viruses cause human disease, with sudden fever and joint inflammation that can persist for long periods. CHIKV is the causative agent of large outbreaks worldwide, and MAYV infection represents a growing public health concern in Latin America, causing sporadic cases and geographically limited outbreaks. Considering the relationship between CHIKV and MAYV, the present study aimed to evaluate if preexisting CHIKV immunity protects against MAYV infection. Immunocompetent C57BL/6 mice were intraperitoneally infected with CHIKV and, 4 weeks later, they were infected with MAYV in their hind paw. We observed that the preexistence of CHIKV immunity conferred partial cross-protection against secondary MAYV infection, reducing disease severity, tissue viral load, and histopathological scores. Interestingly, CHIKV antibodies from humans and mice showed low cross-neutralization to MAYV, but neutralizing activity significantly increased after secondary infection. Furthermore, depletion of adaptive immune cells (CD4(+) T, CD8(+) T, and CD19(+) B cells) did not alter the cross-protection phenotype, suggesting that distinct cell subsets or a combination of adaptive immune cells stimulated by CHIKV are responsible for the partial cross-protection against MAYV. The reduction of proinflammatory cytokines, such as interferon gamma (IFN-gamma), in animals secondarily infected by MAYV, suggests a role for innate immunity in cross-protection. Our findings shed light on how preexisting immunity to arthritogenic alphaviruses may affect secondary infection, which may further develop relevant influence in disease outcome and viral transmission.IMPORTANCE Mosquito-borne viruses have a worldwide impact, especially in tropical climates. Chikungunya virus has been present mostly in developing countries, causing millions of infections, while Mayaro virus, a close relative, has been limited to the Caribbean and tropical regions of Latin America. The potential emergence and spread of Mayaro virus to other high-risk areas have increased the scientific community's attention to an imminent worldwide epidemic. Here, we designed an experimental protocol of chikungunya and Mayaro virus mouse infection, which develops a measurable and quantifiable disease that allows us to make inferences about potential immunological effects during secondary virus infection. Our results demonstrate that previous chikungunya virus infection is able to reduce the severity of clinical outcomes during secondary Mayaro infection. We provide scientific understanding of immunological features during secondary infection with the closely related virus, thus assisting in better comprehending viral transmission and the pathological outcome of these diseases.