Inhibition of respiratory syncytial virus of subgroups A and B using deoxyribozyme DZ1133 in mice.
Respiratory syncytial virus (RSV) commonly infects the upper and lower respiratory tracts. Currently, there is no effective treatment available. Deoxyribozymes are a potential therapeutic for RSV and their activity is based on the ability to bind and cleave complementary RNA sequences to inhibit protein expression. DZ1133 is a deoxyribozyme that targets the conserved genomic RNA sequence of the RSV nucleocapsid protein and has been shown to significantly inhibit various strains of RSV including subgroups A and B, standard A2 and CH18537 strains, and CQ381513, CQ381170, BJ01 and BJ04 strains. Treatment with DZ1133 decreased viral plaque formation in lungs of RSV-infected BALB/c mice. In addition, viral mRNA expression was reduced, airway inflammation was alleviated, and leukocyte counts were reduced in bronchoalveolar lavage fluid of RSV-infected mice. The antiviral effect of DZ1133 was dose-dependent (0.2-0.8mg) and more efficient than antisense oligonucleotide inhibition of gene expression. However, levels of cytokines TNF-alpha, IFN-gamma, IL-12, and IL-10 induced by RSV infection were not affected by DZ1133 treatment. Our data demonstrate that DZ1133 is a potential therapeutic agent against both subgroups A and B RSV infection in vivo.
Zhou
Juan
J
Department of Immunology, Children's Hospital Affiliated to Chongqing University Medical School, Chongqing, China.
Yang
Xi-Qiang
XQ
Xie
Yuan-Yuan
YY
Zhao
Xiao-Dong
XD
Jiang
Li-Ping
LP
Wang
Li-Jia
LJ
Cui
Yu-Xia
YX
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis; D021881:DNA, Catalytic / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000473:pathology; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000302:isolation & purification; D010948:Viral Plaque Assay