Targeting Marek's disease virus by RNA interference delivered from a herpesvirus vaccine

被引:27
作者
Lambeth, Luke S. [1 ]
Zhao, Yuguang [1 ]
Smith, Lorraine P. [1 ]
Kgosana, Lydia [1 ]
Nair, Venugopal [1 ]
机构
[1] Inst Anim Hlth, Div Microbiol, Compton RG20 7NN, Berks, England
基金
英国生物技术与生命科学研究理事会;
关键词
RNA interference; Marek's disease virus; Herpesvirus of turkeys; BACTERIAL ARTIFICIAL CHROMOSOME; CHICKEN U6 PROMOTERS; SHORT HAIRPIN RNA; MAMMALIAN-CELLS; TURKEY HERPESVIRUS; IN-VIVO; REPLICATION; INHIBITION; EXPRESSION; INFECTION;
D O I
10.1016/j.vaccine.2008.10.023
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Live attenuated herpesvirus vaccines such as herpesvirus of turkey (HVT) have been used since 1970 for the control of Marek's disease (MD), a highly infectious lymphoproliferative disease of poultry. Despite the success of these vaccines in reducing losses from the disease, Marek's disease virus (MDV) strains have shown a continuing increase in virulence, presumably due to the inability of the current vaccines in preventing MDV replication. The highly specific and effective nature of RNA interference (RNAi) makes this technology particularly attractive for new antiviral strategies. In order to exploit the power of RNAi-mediated suppression of MDV replication in vivo delivered through existing vaccines, we engineered recombinant HVT expressing short hairpin RNA (shRNA) against MDV genes gB and UL29. The levels of protection induced by the RNAi-expressing HVT against virulent virus challenge were similar to the parent pHVT3 virus. However, chickens vaccinated with recombinant HVT expressing shRNA showed moderate reduction of challenge virus replication in blood and feather samples. Delivery of RNAi-based gene silencing through live attenuated vaccines for reducing replication of pathogenic viruses is a novel approach for the control of infectious diseases. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:298 / 306
页数:9
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