Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
Department of Preclinical Sciences, Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman, Kampar, Malaysia.
J Gen Virol. 2023 Apr;104(4). doi: 10.1099/jgv.0.001842.
Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus, which causes epidemics of fever, joint pain and rash. There are three genotypes: West African, East/Central/South/Africa (ECSA) and Asian, with the latter two predominant globally. Genotype-specific differences in clinical presentations, virulence and immunopathology have been described. Macrophages are key cells in immune responses against CHIKV. Circulating blood monocytes enter tissue to differentiate into monocyte-derived macrophages (MDMs) in response to CHIKV infection at key replication sites such as lymphoid organs and joints. This study analyses differences in replication and induced immune mediators following infection of MDMs with Asian and ECSA CHIKV genotypes. Primary human MDMs were derived from residual blood donations. Replication of Asian (MY/06/37348) or ECSA (MY/08/065) genotype strains of CHIKV in MDMs was measured by plaque assay. Nineteen immune mediators were measured in infected cell supernatants using multiplexed immunoassay or ELISA. MY/08/065 showed significantly higher viral replication at 24 h post-infection (h p.i.) but induced significantly lower expression of proinflammatory cytokines (CCL-2, CCL-3, CCL-4, RANTES and CXCL-10) and the anti-inflammatory IL-1Ra compared to MY/06/37348. No differences were seen at later time points up to 72 h p.i. During early infection, MY/08/065 induced lower proinflammatory immune responses in MDMs. , this may lead to poorer initial control of viral infection, facilitating CHIKV replication and dissemination to other sites such as joints. This may explain the consistent past findings that the ECSA genotype is associated with greater viremia and severity of symptoms than the Asian genotype. Knowledge of CHIKV genotype-specific immunopathogenic mechanisms in human MDMs is important in understanding of clinical epidemiology, biomarkers and therapeutics in areas with co-circulation of different genotypes.
基孔肯雅热病毒（CHIKV）是一种重新出现的蚊媒病毒，可引起发热、关节痛和皮疹的流行。它有三个基因型：西非型、东/中非/南非型（ECSA）和亚洲型，后两种在全球更为常见。已描述了基因型特异性在临床表现、毒力和免疫病理学方面的差异。巨噬细胞是针对 CHIKV 的免疫反应的关键细胞。循环血液单核细胞进入组织，在淋巴器官和关节等关键复制部位响应 CHIKV 感染分化为单核细胞衍生的巨噬细胞（MDMs）。本研究分析了亚洲和 ECSA CHIKV 基因型感染 MDM 后复制和诱导的免疫介质的差异。从剩余的血液供体中分离出原代人 MDM。通过噬斑测定法测量 MDM 中亚洲（MY/06/37348）或 ECSA（MY/08/065）基因型株的 CHIKV 复制。使用多重免疫测定法或 ELISA 测量感染细胞上清液中的 19 种免疫介质。在感染后 24 小时（h p.i.），MY/08/065 显示出明显更高的病毒复制，但与 MY/06/37348 相比，诱导的促炎细胞因子（CCL-2、CCL-3、CCL-4、RANTES 和 CXCL-10）和抗炎性白细胞介素 1 受体（IL-1Ra）的表达明显降低。在高达 72 h p.i.的后期时间点未观察到差异。在早期感染中，MY/08/065 在 MDM 中诱导的促炎免疫反应较低。在感染的早期阶段，这种情况可能导致对病毒感染的初始控制较差，从而促进 CHIKV 的复制和传播到其他部位，如关节。这可以解释过去的一致发现，即 ECSA 基因型与亚洲基因型相比，与更高的病毒血症和症状严重程度相关。了解 CHIKV 基因型特异性的免疫发病机制在人类 MDM 中对于理解不同基因型共存地区的临床流行病学、生物标志物和治疗方法非常重要。
