Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
Institute for Virology, FB10-Veterinary Medicine, Justus-Liebig University, Giessen, Germany.
J Virol. 2022 Jul 13;96(13):e0059922. doi: 10.1128/jvi.00599-22. Epub 2022 Jun 13.
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne orthonairovirus that causes a severe, often fatal, hemorrhagic disease throughout Africa, Asia, and Southeast Europe. A wide variety of strains are circulating in the field which broadly correlate to their geographic distribution. The viral determinants of pathogenicity remain unclear, as does the contribution of strain-specific differences to pathology. Aigai virus (AIGV) is a closely related virus (formally designated CCHFV genotype VI, Europe II, or AP92-like virus), which has been proposed to be less virulent than CCHFV. However, the molecular details leading to potential differences in virulence are unknown. To explore if differences exist, life cycle modeling systems, including both a minigenome and a transcriptionally competent virus-like particle assay, were developed for AIGV to allow the comparison with the CCHFV reference IbAr10200 strain. Using this approach, we could demonstrate that AIGV exhibits lower viral gene expression than the reference strain of CCHFV. Subsequent systematic exchange of viral components revealed that the L protein is responsible for the observed differences in gene expression and that the interferon (IFN) antagonistic activity of the ovarian tumor-type protease domain is not responsible for this effect. Crimean-Congo hemorrhagic fever virus (CCHFV) is the cause of severe hemorrhagic disease, which is often fatal. Present throughout Africa, Asia, and Southeast Europe, a diverse number of viral genotypes exist. However, the viral determinants of pathogenicity remain unclear. It has been proposed that the closely related Aigai virus (AIGV) may be a less virulent virus. Here, using newly developed and improved life cycle modeling systems we have examined potential differences between the CCHFV reference strain, IbAr10200, and AIGV. Using this approach, we identified lower viral gene expression driven by the AIGV viral polymerase as a major difference which may be indicative of lower virulence.
克里米亚-刚果出血热病毒（CCHFV）是一种蜱媒正呼肠孤病毒，可引起整个非洲、亚洲和东南欧地区严重的、经常致命的出血性疾病。广泛存在于野外的各种病毒株与它们的地理分布密切相关。病毒致病性的决定因素仍不清楚，而株特异性差异对病理学的贡献也不清楚。Aigai 病毒（AIGV）是一种密切相关的病毒（正式指定为 CCHFV 基因型 VI、欧洲 II 或 AP92 样病毒），据提议，其毒力比 CCHFV 弱。然而，导致潜在毒力差异的分子细节尚不清楚。为了探索是否存在差异，我们开发了包括 minigenome 和转录有效的病毒样颗粒测定在内的生命循环建模系统，用于 AIGV，以允许与 CCHFV 参考株 IbAr10200 进行比较。使用这种方法，我们可以证明 AIGV 的病毒基因表达低于参考株 CCHFV。随后对病毒成分的系统交换表明，L 蛋白是导致观察到的基因表达差异的原因，而卵巢肿瘤型蛋白酶结构域的干扰素（IFN）拮抗活性不是这种效应的原因。克里米亚-刚果出血热病毒（CCHFV）是引起严重出血性疾病的原因，这种疾病通常是致命的。它存在于整个非洲、亚洲和东南欧，存在多种病毒基因型。然而，病毒致病性的决定因素仍不清楚。有人提出，密切相关的 Aigai 病毒（AIGV）可能是一种毒力较弱的病毒。在这里，我们使用新开发和改进的生命循环建模系统，检查了 CCHFV 参考株 IbAr10200 与 AIGV 之间的潜在差异。使用这种方法，我们确定了由 AIGV 病毒聚合酶驱动的较低病毒基因表达是一个主要差异，这可能表明较低的毒力。
