Department of Microbiology, Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon, 200-702, Republic of Korea.
J Microbiol. 2013 Dec;51(6):866-71. doi: 10.1007/s12275-013-3428-7. Epub 2013 Dec 19.
Influenza viruses are seasonally recurring human pathogens. Vaccines and antiviral drugs are available for influenza. However, the viruses, which often change themselves via antigenic drift and shift, demand constant efforts to update vaccine antigens every year and develop new agents with broad-spectrum antiviral efficacy. An animal model is critical for such efforts. While most human influenza viruses are unable to kill BALB/c mice, some strains have been shown to kill DBA/2 mice without prior adaptation. Therefore, in this study, we explored the feasibility of employing DBA/2 mice as a model in the development of anti-influenza drugs. Unlike the BALB/c strain, DBA/2 mice were highly susceptible and could be killed with a relatively low titer (50% DBA/2 lethal dose = 10(2.83) plaque-forming units) of the A/Korea/01/2009 virus (2009 pandemic H1N1 virus). When treated with a neuraminidase inhibitor, oseltamivir phosphate, infected DBA/2 mice survived until 14 days post-infection. The reduced morbidity of the infected DBA/2 mice was also consistent with the oseltamivir treatment. Taking these data into consideration, we propose that the DBA/2 mouse is an excellent animal model to evaluate antiviral efficacy against influenza infection and can be further utilized for combination therapies or bioactivity models of existing and newly developed anti-influenza drugs.
流感病毒是季节性反复发作的人类病原体。有疫苗和抗病毒药物可用于流感。然而,这些病毒经常通过抗原漂移和转变来自我改变,因此需要不断努力每年更新疫苗抗原,并开发具有广谱抗病毒疗效的新药物。动物模型对于这些努力至关重要。虽然大多数人类流感病毒不能杀死 BALB/c 小鼠,但有些菌株已经被证明可以在未经适应的情况下杀死 DBA/2 小鼠。因此,在这项研究中,我们探讨了将 DBA/2 小鼠用作抗流感药物开发模型的可行性。与 BALB/c 株不同,DBA/2 小鼠高度易感,并且可以用相对较低的病毒滴度(A/Korea/01/2009 病毒(2009 年大流行 H1N1 病毒)的 50% DBA/2 致死剂量=10(2.83)噬菌斑形成单位)杀死。当用神经氨酸酶抑制剂奥司他韦磷酸盐治疗时,感染的 DBA/2 小鼠存活到感染后 14 天。感染的 DBA/2 小鼠发病率降低也与奥司他韦治疗一致。考虑到这些数据,我们提出 DBA/2 小鼠是评估抗流感感染抗病毒疗效的优秀动物模型,并且可以进一步用于现有和新开发的抗流感药物的联合治疗或生物活性模型。