کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10967387 | 1102826 | 2013 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Neurovirulent flavivirus can be attenuated in mice by incorporation of neuron-specific microRNA recognition elements into viral genome
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Engineering viruses by inserting microRNA (miRNA) recognition elements (MREs) into the 3â²-untranslated region (3â²-UTR) of viral RNA can efficiently restrict viral tissue tropism. We used the mosquito-borne Japanese encephalitis virus (JEV) to investigate whether endogenous neuron-specific microRNA-124 (miR-124) could be used to restrict viral neurotropism and, consequently, diminish the neurovirulence of JEV in mice. To recover a neuron-restricted JEV, we inserted 2 copies of a perfectly matched MRE specific to miR-124 into the 3â²-UTR to create infectious JEV recombinant RP-124PT (rRP-124PT). The effect of rRP-124PT was attenuated in infected mice as compared with MRE mutant and parental strains, both of which were lethal to challenged mice. Immunization with rRP-124PT appeared to elicit full protective immunity against subsequent JEV lethal challenge. We found neurons of the central nervous system critical targets for infection by JEV, which directly causes lethal encephalitis. The silencing of JEV rRP-124PT in mice by miR-124 illustrates that endogenous miRNA can readily recognize and interact with the 3â²-UTR of naturally occurring genomic/mRNAs lacking a polyadenylated tail. Inserting MREs into viral RNA may facilitate further study of flaviviral pathogenesis involving tissue tropism and suggest an additional layer of biosafety for the rational design of safe flavivirus vaccines.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vaccine - Volume 31, Issue 49, 2 December 2013, Pages 5915-5922
Journal: Vaccine - Volume 31, Issue 49, 2 December 2013, Pages 5915-5922
نویسندگان
Li-Chen Yen, Yi-Ling Lin, Hsiang-Hsuan Sung, Jia-Teh Liao, Chang-Huei Tsao, Chih-Mao Su, Chih-Kung Lin, Ching-Len Liao,