Taylor Travis J, Diaz Fernando, Colgrove Robert C, Bernard Kristen A, DeLuca Neal A, Whelan Sean P J, Knipe David M
Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States.
Wadsworth Center, New York State Department of Health, P.O Box 509, Albany, NY 12201, United States.
Virology. 2016 Sep;496:186-193. doi: 10.1016/j.virol.2016.06.006. Epub 2016 Jun 20.
West Nile virus (WNV) is a flavivirus that swept rapidly across North America in 1999, declined in prevalence, and then resurged in 2012. To date, no vaccine is available to prevent infection in the human population. Herpes simplex virus (HSV) replication-defective vaccine vectors induce a durable immunity characterized by strong antibody and CD8(+) T cell responses even in HSV-immune animals. In this study, a WNV protein expression cassette was optimized for virus-like particle (VLP) production in transfection studies, and the cassette was recombined into an HSV-1 d106-WNV virus vector, which produced extracellular VLPs, as confirmed by immunoelectron microscopy. Immunization of mice with the d106-WNV recombinant vector elicited a specific anti-WNV IgG response. This study highlights the flavivirus coding sequences needed for efficient assembly of virus-like particles. This information will facilitate generation of additional vaccine vectors against other flaviviruses including the recently emerged Zika virus.
西尼罗河病毒（WNV）是一种黄病毒，于1999年迅速席卷北美，流行率下降，然后在2012年再次出现。迄今为止，尚无疫苗可预防人群感染。单纯疱疹病毒（HSV）复制缺陷型疫苗载体即使在HSV免疫的动物中也能诱导以强大抗体和CD8(+) T细胞反应为特征的持久免疫力。在本研究中，优化了WNV蛋白表达盒以用于转染研究中的病毒样颗粒（VLP）生产，并将该表达盒重组到HSV-1 d106-WNV病毒载体中，经免疫电子显微镜证实，该载体产生细胞外VLP。用d106-WNV重组载体免疫小鼠可引发特异性抗WNV IgG反应。本研究突出了有效组装病毒样颗粒所需的黄病毒编码序列。这些信息将有助于生成针对其他黄病毒（包括最近出现的寨卡病毒）的更多疫苗载体。
