Neurovirulence properties of recombinant vesicular stomatitis virus vectors in non-human primates
Neurovirulence properties of recombinant vesicular stomatitis virus vectors in non-human primates
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DOI：
10.1016/j.virol.2006.10.026
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发表时间：
2007-03-30
期刊：
影响因子：
3.7
通讯作者：
Udem, Stephen A.
中科院分区：
文献类型：
--
作者：
Johnson, J. Erik;Nasar, Farooq;Udem, Stephen A.
虽然水疱性口炎病毒（VSV）在啮齿动物中的神经毒力和致病性已经得到了很好的研究，但对VSV在非人类灵长类动物中的致病性知之甚少。为了解决这个问题，我们测量了猕猴的VSV病毒血症、脱落和神经毒力。在鼻内接种后，猕猴在接种后1天的鼻洗液中传播了少量重组VSV (rVSV)；未检测到病毒血症。在对猕猴进行鼻内接种后，野生型VSV、rVSV和两种rVSV- hiv载体没有显示向中枢神经系统组织传播的证据。然而，在猕猴体内接种了wt VSV病毒后，它们出现了严重的神经系统疾病。4只接受rVSV感染的猕猴中有1只出现了与wt组相似的临床和组织学症状，而该组中的其余3只猕猴以及rVSV- hiv载体组中的所有猕猴均未出现疾病的临床症状，并且与wt组相比，组织病理学严重程度有所降低。讨论了这些发现对rVSV疫苗开发的意义。(c) 2006爱思唯尔公司版权所有。
Although vesicular stomatitis virus (VSV) neurovirulence and pathogenicity in rodents have been well studied, little is known about VSV pathogenicity in non-human primates. To address this question, we measured VSV viremia, shedding, and neurovirulence in macaques. Following intranasal inoculation, macaques shed minimal recombinant VSV (rVSV) in nasal washes for 1 day post-inoculation; viremia was not detected. Following intranasal inoculation of macaques, wild type (wt) VSV, rVSV, and two rVSV-HIV vectors showed no evidence of spread to CNS tissues. However, macaques inoculated intrathalamically with wt VSV developed severe neurological disease. One of four macaques receiving rVSV developed clinical and histological signs similar to the wt group, while the remaining three macaques in this group and all of the macaques in the rVSV-HIV vector groups showed no clinical signs of disease and reduced severity of histopathology compared to the wt group. The implications of these findings for rVSV vaccine development are discussed. (c) 2006 Elsevier Inc. All rights reserved.