Abstract:
Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease in livestock and humans. Whilst initially restricted to the African continent, recent spread to the Arabian Peninsula has highlighted the likelihood of entry into new regions. Due to the absence of a regulatory-approved human vaccine, work is ongoing to develop and assess countermeasures. As such, small animal models play a pivotal role in providing information on disease pathogenesis and elucidating which intervention strategies confer protection. To develop and establish the BALB/c mouse model, we challenged mice with RVFV grown from two separate cell lines: one derived from mosquitoes (C6/36) and the other mammalian derived (Vero E6). Following infection, we assessed the clinical course of disease progression at days 1 and 3 post-challenge and evaluated viral tropism and immune analytes. The results demonstrated that RVFV infection was affected by the cell line used to propagate the challenge virus, with those grown in insect cells resulting in a more rapid disease progression. The lowest dose that caused uniform severe disease remained the same across both virus preparations. In addition, to demonstrate reproducibility, the lowest dose was used for a subsequent infection study using male and female animals. The results further demonstrated that male mice succumbed to infection more rapidly than their female counterparts. Our results establish an RVFV mouse model and key parameters that affect the course of disease progression in BALB/c mice.
摘要:
裂谷热病毒(RVFV)是一种蚊子传播的人畜共患病原体,可在牲畜和人类中引起疾病。虽然最初仅限于非洲大陆,最近向阿拉伯半岛的传播突显了进入新地区的可能性。由于缺乏监管部门批准的人类疫苗,制定和评估对策的工作正在进行中。因此,小动物模型在提供有关疾病发病机制的信息和阐明哪些干预策略赋予保护作用中起着关键作用。建立BALB/c小鼠模型,我们用从两种不同细胞系生长的RVFV攻击小鼠:一种来源于蚊子(C6/36),另一种来源于哺乳动物(VeroE6)。感染后,我们评估了攻击后第1天和第3天疾病进展的临床过程,并评估了病毒嗜性和免疫分析物.结果表明,RVFV感染受到用于繁殖攻击病毒的细胞系的影响,那些在昆虫细胞中生长的细胞导致疾病进展更快。引起均匀严重疾病的最低剂量在两种病毒制剂中保持相同。此外,为了证明重现性,最低剂量用于随后使用雄性和雌性动物的感染研究.结果进一步证明,雄性小鼠比雌性小鼠更快地屈服于感染。我们的结果在BALB/c小鼠中建立了RVFV小鼠模型和影响疾病进展过程的关键参数。