Galveston National Laboratory, Institute for Human Infection and Immunity, Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
Galveston National Laboratory, Institute for Human Infection and Immunity, Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathologies, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Antiviral Res. 2022 Nov;207:105401. doi: 10.1016/j.antiviral.2022.105401. Epub 2022 Aug 29.
Crimean-Congo hemorrhagic fever (CCHF) is a medically relevant tick-borne viral disease caused by the Bunyavirus, Crimean-Congo hemorrhagic fever virus (CCHFV). CCHFV is endemic to Asia, the Middle East, South-eastern Europe, and Africa and is transmitted in enzootic cycles among ticks, mammals, and birds. Human infections are mostly subclinical or limited to mild febrile illness. Severe disease may develop, resulting in multi-organ failure, hemorrhagic manifestations, and case-fatality rates up to 30%. Despite the widespread distribution and life-threatening potential, no treatments have been approved for CCHF. Antiviral inhibitory peptides, which antagonize viral entry, are licensed for clinical use in certain viral infections and have been experimentally designed against human pathogenic bunyaviruses, with in vitro and in vivo efficacies. We designed inhibitory peptides against CCHFV with and without conjugation to various polyethylene glycol and sterol groups. These additions have been shown to enhance both cellular uptake and antiviral activity. Peptides were evaluated against pseudotyped and wild-type CCHFV via neutralization tests, Nairovirus fusion assays, and cytotoxicity profiling. Four peptides neutralized CCHFV with two of these peptides shown to inhibit viral fusion. This work represents the development of experimental countermeasures for CCHF, describes a nairovirus immunofluorescence fusion assay, and illustrates the utility of pseudotyped CCHFV for the screening of entry antagonists at low containment settings for CCHF.
克里米亚-刚果出血热（CCHF）是一种由布尼亚病毒引起的具有医学意义的蜱传病毒性疾病。CCHFV 地方性流行于亚洲、中东、东南欧和非洲，在蜱、哺乳动物和鸟类之间的地方性循环中传播。人类感染大多为亚临床或仅限于轻度发热性疾病。严重疾病可能发展，导致多器官衰竭、出血表现和病死率高达 30%。尽管分布广泛且有生命威胁，但尚未批准任何治疗方法用于 CCHF。抗病毒抑制肽可拮抗病毒进入，已在某些病毒感染中获得许可用于临床，并且已针对人类致病性布尼亚病毒进行了实验设计，具有体外和体内疗效。我们设计了针对 CCHFV 的抑制肽，不与各种聚乙二醇和固醇基团缀合。已证明这些添加物可增强细胞摄取和抗病毒活性。通过中和试验、纳罗病毒融合测定和细胞毒性分析，评估了针对假型和野生型 CCHFV 的肽。四种肽可中和 CCHFV，其中两种肽可抑制病毒融合。这项工作代表了针对 CCHF 的实验性对策的发展，描述了一种纳罗病毒免疫荧光融合测定，并说明了假型 CCHFV 在低 CCHF 容纳条件下用于筛选进入拮抗剂的效用。
