tailieunhanh - Báo cáo y học: " Effective inhibition of HCMV UL49 gene expression and viral replication by oligonucleotide external guide sequences and RNase P"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Effective inhibition of HCMV UL49 gene expression and viral replication by oligonucleotide external guide sequences and RNase P | Zhang et al. Virology Journal 2010 7 100 http content 7 1 100 VIROLOGY JOURNAL RESEARCH Open Access Effective inhibition of HCMV UL49 gene expression and viral replication by oligonucleotide external guide sequences and RNase P WenJun Zhang 1 2 HongJian Li1 YueQin Li1 ZhiFeng Zeng1 ShiQian Li1 Xin Zhang1 Yi Zou1 and TianHong Zhou 1 Abstract Background Human cytomegalovirus HCMV is a ubiquitous herpesvirus that typically causes asymptomatic infections in healthy individuals but may lead to serious complications in newborns and immunodeficient individuals. The emergence of drug-resistant strains of HCMV has posed a need for the development of new drugs and treatment strategies. Antisense molecules are promising gene-targeting agents for specific regulation of gene expression. External guide sequences EGSs are oligonucleotides that consist of a sequence complementary to a target mRNA and recruit intracellular RNase P for specific degradation of the target RNA. The UL49-deletion BAC of HCMV was significantly defective in growth in human foreskin fibroblasts. Therefore UL49 gene may serve as a potential target for novel drug development to combat HCMV infection. In this study DNA-based EGS molecules were synthesized to target the UL49 mRNA of human cytomegalovirus HCMV . Results By cleavage activity assessing in vitro the EGS aimed to the cleavage site 324 nt downstream from the translational initiation codon of UL49 mRNA . EGS324 was confirmed be efficient to direct human RNase P to cleave the target mRNA sequence. When EGS324 was exogenously administered into HCMV-infected human foreskin fibroblasts HFFs a significant reduction of 76 in the mRNA and 80 in the protein expression of UL49 gene comparing with the cells transfected with control EGSs. Furthermore a reduction of about 330-fold in HCMV growth were observed in HCMV-infected HFFs treated with the EGS. Conclusions These results indicated that UL49 gene was essential for replication of HCMV.