Intranasal Exposure to Rift Valley Fever Virus Live-Attenuated Strains Leads to High Mortality Rate in Immunocompetent Mice.

Intranasal Exposure to Rift Valley Fever Virus Live-Attenuated Strains Leads to High Mortality Rate in Immunocompetent Mice.
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DOI:
10.3390/v14112470
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发表时间:
2022-11-08
期刊:
Viruses
影响因子:
--
通讯作者:
--
中科院分区:
其他
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--
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裂谷热病毒(RVFV)是一种节肢动物传播的致病病毒,可导致反刍动物和人类严重疾病。该病毒可以通过节肢动物叮咬或接触受污染的液体或组织传播。两种减毒活兽用疫苗——Smithburn (SB) 和 Clone 13 (Cl.13)——目前在非洲流行病期间使用。然而,它们的残留致病性(即 SB)或潜在的逆转(即 Cl.13)会造成严重的不利影响,严重限制了它们在现场的使用。在本研究中,我们通过皮下或鼻内接种用 SB 或 Cl.13 感染免疫活性小鼠。有趣的是,我们发现,与皮下感染不同,鼻内接种导致的死亡率很高。此外,我们在 SB 和 Cl.13 感染小鼠的大脑中检测到高滴度和病毒 N 抗原水平。总体而言,我们揭示了SB和Cl.13的致病性和给药途径之间存在明显的相关性,鼻内接种比皮下感染具有更强的神经毒力和更高的死亡率。
Rift Valley fever virus (RVFV) is a pathogenic arthropod-borne virus that can cause serious illness in both ruminants and humans. The virus can be transmitted by an arthropod bite or contact with contaminated fluids or tissues. Two live-attenuated veterinary vaccines—the Smithburn (SB) and Clone 13 (Cl.13)—are currently used during epizootic events in Africa. However, their residual pathogenicity (i.e., SB) or potential of reversion (i.e., Cl.13) causes important adverse effects, strongly limiting their use in the field. In this study, we infected immunocompetent mice with SB or Cl.13 by a subcutaneous or an intranasal inoculation. Interestingly, we found that, unlike the subcutaneous infection, the intranasal inoculation led to a high mortality rate. In addition, we detected high titers and viral N antigen levels in the brain of both the SB- and Cl.13-infected mice. Overall, we unveil a clear correlation between the pathogenicity and the route of administration of both SB and Cl.13, with the intranasal inoculation leading to a stronger neurovirulence and higher mortality rate than the subcutaneous infection.
MAVS介导了大脑中的保护性免疫反应,以促进裂谷发烧病毒。
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