Selection of an aptamer against rabies virus: a new class of molecules with antiviral activity.
Rabies is a fatal central nervous system (CNS) disease caused by the neurotropic rabies virus (RABV). The therapeutic management of RABV infections is still problematic, and novel antiviral strategies are urgently required. We established the RVG-BHK-21 cell line, which expresses RABV glycoprotein on the cell surface, to select aptamers. Through 28 iterative rounds of selection, single-stranded DNA (ssDNA) aptamers were generated by exponential enrichment (SELEX). A virus titer assay and a real-time quantitative reverse transcription PCR (qRT-PCR) assay revealed that four aptamers could inhibit the replication of RABV in cultured baby hamster kidney (BHK)-21 cells. However, the aptamers did not inhibit the replication of other virus, e.g., canine distemper virus (CDV) and canine parvovirus (CPV). In addition, the GE54 aptamer was found to effectively protect mice against lethal RABV challenge. After inoculation with aptamers for 24h or 48h, followed by inoculation with CVS-11, approximately 25-33% of the mice survived. In summary, we selected aptamers that could significantly protect from a lethal dose of RABV in vitro and in vivo.
Key Laboratory of Fishery Drug Development of Ministry of Agriculture, Pearl River Fishery Research Institute, Chinese Academy of Fishery Sciences, Liwan District, Guangzhou, Guangdong, China; Institute of Military Veterinary, Academy of Military Medical Science, Changchun 130062, China.
Hong-Ru
HR
Liang
Institute of Military Veterinary, Academy of Military Medical Science, Changchun 130062, China.
Gui-Qiu
GQ
Hu
Institute of Military Veterinary, Academy of Military Medical Science, Changchun 130062, China.
Xiang-Hong
XH
Xue
Institute of Military Veterinary, Academy of Military Medical Science, Changchun 130062, China.
Lu
L
Li
Institute of Military Veterinary, Academy of Military Medical Science, Changchun 130062, China.
Xue-Xing
XX
Zheng
Institute of Military Veterinary, Academy of Military Medical Science, Changchun 130062, China.
Yu-Wei
YW
Gao
Institute of Military Veterinary, Academy of Military Medical Science, Changchun 130062, China. Electronic address: yst610223@yahoo.com.cn.
Song-Tao
ST
Yang
Institute of Military Veterinary, Academy of Military Medical Science, Changchun 130062, China. Electronic address: Xia_xzh@yahoo.com.cn.
Xian-Zhu
XZ
Xia
D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology* / Q000627:therapeutic use; D052157:Aptamers, Nucleotide / Q000302:isolation & purification* / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D018890:Chemoprevention / Q000379:methods; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D008807:Mice, Inbred BALB C; D011818:Rabies / Q000517:prevention & control; D011820:Rabies virus / Q000187:drug effects* / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D052156:SELEX Aptamer Technique; D016019:Survival Analysis; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D052157:Aptamers, Nucleotide
Aptamer; Rabies virus; Therapeutic agents