Effects of deoxyribozyme against respiratory syncytial virus infection in mice with different immune functions

Abstract

Objective To investigate the effects of deoxyribozyme(DZ) against respiratory syncytial virus(RSV) infection in BALB/c mice and nude mice. Methods RSV infected BALB/c mice and nude mice were nasally dripped with DZ. Pulmonary viral titers were detected by plaque forming experiment,and viral mRNA expression was assayed by RT-PCR. Leukocytes and the subgroup cells in bronchoalveolar lavage fluid (BALF) were counted, cytokines of TNF-α, IL-12, IFN-γand IL-10 in BALF were assayed by ELISA. Pulmonary histopathology was examined to realize the inflammation of airway. Results Pulmonary titers of 0.2 mg, 0.4 mg and 0.8 mg DZ treated BALB/c mice were lg(3.65 ±0.12) PFU/g lung,lg( 3.25 ± 0.10) PFU/g lung and lg( 3.03 ±0.08 ) PFU/g lung, decreased as compared with that of infected control BALB/c mice lg(4.35 ± 0.11 ) PFU/g lung ( P<0.05 ). Meanwhile viral titers of 0.2 mg,0.4 mg and 0.8 mg DZ treated nude mice were lg(4.82 ±0.15) PFU/g lung, lg(4.47 ±0.12) PFU/g lung and lg(4.21 ±0.11 ) PFU/g lung, declined dramatically as compared with that of infected control nude mice lg(6.23 ± 0.15) PFU/g lung( P<0.01 ). 0.2 mg, 0.4 mg and 0.8 mg DZ reduced BALB/c mice pulmonary viral mRNA expression by 30.51% ,47.38% ( P<0.05 ) and 53.97% ( P<0.01 ) and nude mice by 36.59% (P ＜0.05 ), 48.72%, 59.78% ( P<0.01 ) respectively as compared with their infected control groups. In 0.4 mg DZ treated BALB/c mice and nude mice, total numbers of leukocytes in BALF were decreased dramatically and pulmonary histology was significantly improved compared with their infected controls( P<0.05 ). And the treatment of 0.4 mg DZ reduced productions of TNF-α, IL-12 and IFN-γin BALF of RSV infected nude mice ( P<0.05 ). Conclusion DZ effectively inhibits viral replication and reduces airway inflammation in RSV infected BALB/c mice and nude mice, and the effects in nude mice are more significant. DZ is a potential therapeutic agent against RSV infection in vivo. Key words: Respiratory syncytial virus; Deoxyribozyme; Immunity; Genetic therapy