克里米亚-刚果出血热病毒(CCHFV)是一种蜱传播的正负病毒,往往是致命的,整个非洲的出血性疾病,亚洲,和东南欧。各种各样的菌株在田间循环,其广泛地与它们的地理分布相关。致病性的病毒决定因素仍不清楚,菌株特异性差异对病理学的贡献也是如此。艾盖病毒(AIGV)是一种密切相关的病毒(正式指定CCHFV基因型VI,欧洲II,或类AP92病毒),它被认为比CCHFV毒性小。然而,导致毒力潜在差异的分子细节是未知的。探索是否存在差异,生命周期建模系统,包括小基因组和转录能力的病毒样颗粒测定,为AIGV开发,以允许与CCHFV参考IbAr10200菌株进行比较。使用这种方法,我们可以证明AIGV表现出比CCHFV参考株更低的病毒基因表达。随后的病毒成分的系统交换表明,L蛋白负责观察到的基因表达差异,而卵巢肿瘤型蛋白酶结构域的干扰素(IFN)拮抗活性不负责这种作用。重要性克里米亚-刚果出血热病毒(CCHFV)是严重出血性疾病的原因,这往往是致命的。在整个非洲,亚洲,和东南欧,存在多种病毒基因型。然而,致病性的病毒决定因素仍不清楚.已经提出密切相关的艾盖病毒(AIGV)可能是毒性较低的病毒。这里,使用新开发和改进的生命周期建模系统,我们检查了CCHFV参考应变之间的潜在差异,IbAr10200和AIGV。使用这种方法,我们确定由AIGV病毒聚合酶驱动的较低病毒基因表达是一个主要差异,这可能表明毒力较低。
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. IMPORTANCE 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.