Ogata Norio, Shibata Takashi
Research Institute, Taiko Pharmaceutical Co. Ltd, 3-34-14 Uchihonmachi, Suita, Osaka 564-0032, Japan.
J Gen Virol. 2008 Jan;89(Pt 1):60-67. doi: 10.1099/vir.0.83393-0.
Influenza virus infection is one of the major causes of human morbidity and mortality. Between humans, this virus spreads mostly via aerosols excreted from the respiratory system. Current means of prevention of influenza virus infection are not entirely satisfactory because of their limited efficacy. Safe and effective preventive measures against pandemic influenza are greatly needed. We demonstrate that infection of mice induced by aerosols of influenza A virus was prevented by chlorine dioxide (ClO(2)) gas at an extremely low concentration (below the long-term permissible exposure level to humans, namely 0.1 p.p.m.). Mice in semi-closed cages were exposed to aerosols of influenza A virus (1 LD(50)) and ClO(2) gas (0.03 p.p.m.) simultaneously for 15 min. Three days after exposure, pulmonary virus titre (TCID(50)) was 10(2.6+/-1.5) in five mice treated with ClO(2), whilst it was 10(6.7+/-0.2) in five mice that had not been treated (P=0.003). Cumulative mortality after 16 days was 0/10 mice treated with ClO(2) and 7/10 mice that had not been treated (P=0.002). In in vitro experiments, ClO(2) denatured viral envelope proteins (haemagglutinin and neuraminidase) that are indispensable for infectivity of the virus, and abolished infectivity. Taken together, we conclude that ClO(2) gas is effective at preventing aerosol-induced influenza virus infection in mice by denaturing viral envelope proteins at a concentration well below the permissible exposure level to humans. ClO(2) gas could therefore be useful as a preventive means against influenza in places of human activity without necessitating evacuation.
流感病毒感染是人类发病和死亡的主要原因之一。在人与人之间，这种病毒主要通过呼吸系统排出的气溶胶传播。由于目前预防流感病毒感染的方法效果有限，所以并不完全令人满意。因此，非常需要安全有效的预防大流行性流感的措施。我们证明，极低浓度的二氧化氯（ClO₂）气体（低于人类长期允许接触水平，即0.1 ppm）可预防甲型流感病毒气溶胶诱发的小鼠感染。将半封闭笼子中的小鼠同时暴露于甲型流感病毒（1 LD₅₀）气溶胶和ClO₂气体（0.03 ppm）中15分钟。暴露三天后，用ClO₂处理的五只小鼠的肺病毒滴度（TCID₅₀）为10²·⁶⁺⁻¹·⁵，而未处理的五只小鼠的肺病毒滴度为10⁶·⁷⁺⁻⁰·²（P = 0.003）。16天后，用ClO₂处理的10只小鼠的累积死亡率为0/10，未处理的10只小鼠的累积死亡率为7/10（P = 0.002）。在体外实验中，ClO₂使病毒感染性所必需的病毒包膜蛋白（血凝素和神经氨酸酶）变性，并消除了感染性。综上所述，我们得出结论，ClO₂气体在远低于人类允许接触水平的浓度下通过使病毒包膜蛋白变性，可有效预防小鼠气溶胶诱发的流感病毒感染。因此，ClO₂气体可作为一种预防手段，用于人类活动场所预防流感，而无需人员疏散。
