Kalkan-Yazıcı Merve, Karaaslan Elif, Çetin Nesibe Selma, Hasanoğlu Sevde, Güney Filiz, Zeybek Ümit, Doymaz Mehmet Z
Beykoz Institute of Life Sciences & Biotechnology, Bezmialem Vakif University, Istanbul, Turkey.
Institute of Experimental Medical Research, Department of Molecular Medicine, Istanbul University, Istanbul, Turkey.
J Virol. 2021 Mar 10;95(7). doi: 10.1128/JVI.02156-20. Epub 2021 Jan 13.
The World Health Organization estimates that there may be three billion people at risk of infection by Crimean-Congo Hemorrhagic Fever Virus (CCHFV), a highly lethal, emerging carried by ticks. On the other hand, the closely related Hazara virus (HAZV), a member of the same serogroup, has not been reported as a pathogen for humans. Given the structural and phylogenetic similarities between these two viruses, we evaluated the immunological similarities of the nucleocapsid protein (NP) of these two viruses in multiple species. Strong antigenic similarities were demonstrated in anti-NP humoral immune responses against HAZV and CCHFV in multiple species using convalescent human CCHF sera, rabbit and mouse polyclonal antiserum raised against CCHFV, and mouse polyclonal antiserum against CCHFV-NP in enzyme immunoassays. We also report a convincing cross-reactivity between NPs in Western blots using HAZV-infected cell lysate as antigen and inactivated CCHFV and CCHFV-NP-immunized mice sera. These results suggest that NPs of HAZV and CCHFV share significant similarities in humoral responses across species and underline the potential utility of HAZV as a surrogate model for CCHFV. CCHFV and HAZV, members of the family, are transmitted to mammals by tick bites. CCHFV is considered to be a severe threat to public health and causes hemorrhagic diseases with a high mortality rate, and there are neither preventative nor therapeutic medications against CCHFV disease. HAZV, on the other hand, is not a pathogen to humans and can be studied under BSL-2 conditions. The antigenic relationship between these viruses is of interest for vaccines and for preventative investigations. Here, we demonstrate cross-reactivity in anti-NP humoral immune response between NPs of HAZV and CCHFV in multiple species. These results underline the utility of HAZV as a surrogate model to study CCHFV infection.
世界卫生组织估计，可能有30亿人面临感染克里米亚-刚果出血热病毒（CCHFV）的风险，该病毒具有高度致死性，是一种由蜱传播的新发病毒。另一方面，密切相关的哈扎拉病毒（HAZV），属于同一血清群的成员，尚未被报道为人类病原体。鉴于这两种病毒在结构和系统发育上的相似性，我们评估了这两种病毒的核衣壳蛋白（NP）在多个物种中的免疫相似性。在酶免疫分析中，使用康复期人类CCHF血清、针对CCHFV产生的兔和小鼠多克隆抗血清以及针对CCHFV-NP的小鼠多克隆抗血清，在多个物种中针对HAZV和CCHFV的抗NP体液免疫反应中显示出强烈的抗原相似性。我们还报告了在蛋白质印迹中，以HAZV感染的细胞裂解物为抗原，以及用灭活的CCHFV和CCHFV-NP免疫的小鼠血清，NP之间具有令人信服的交叉反应性。这些结果表明，HAZV和CCHFV的NP在跨物种的体液反应中具有显著相似性，并强调了HAZV作为CCHFV替代模型的潜在效用。CCHFV和HAZV属于 科的成员，通过蜱叮咬传播给哺乳动物。CCHFV被认为是对公共卫生的严重威胁，可导致出血性疾病，死亡率很高，并且没有针对CCHFV疾病的预防或治疗药物。另一方面，HAZV不是人类病原体，可以在生物安全二级条件下进行研究。这些病毒之间的抗原关系对于疫苗和预防研究具有重要意义。在这里，我们证明了HAZV和CCHFV的NP在多个物种中的抗NP体液免疫反应中具有交叉反应性。这些结果强调了HAZV作为研究CCHFV感染替代模型的效用。
