Hou Zongliu, Huang Yongkun, Huan Youming, Pang Wei, Meng Mingyao, Wang Ping, Yang Meifen, Jiang Lihong, Cao Xinan, Wu Kenneth K
Research Laboratory Center, Yan'an Hospital of Kunming City, Kunming, Yunnan, People's Republic of China.
J Pediatr Gastroenterol Nutr. 2008 Apr;46(4):376-85. doi: 10.1097/MPG.0b013e3181661ae4.
Rotavirus infection is the most common cause of infectious diarrhea and gastroenteritis among children worldwide. The viral proteins (VP), especially VP4- and VP7-induced neutralizing antibodies, were considered to be critical in protective immunity to rotavirus disease. However, whether the antibody to rotavirus nonstructural protein 4 (NSP4) protects against rotavirus-induced diarrhea directly is not completely clear, especially for the protective time course.
To obtain direct evidence, 12-day-old ICR mice were treated with NSP4 and entire rotavirus to induce diarrhea.
Both NSP4 and rotavirus-treated mice developed diarrhea, which was accompanied by histological changes in the small intestine compared to age-matched control mice. Anti-NSP4 antibody demonstrated protection against both entire rotavirus-induced diarrhea and NSP4-induced diarrhea. The histological changes in the small intestinal were reversible. These data show that early intervention with anti-NSP4 antibody can prevent rotavirus-induced diarrhea in mice; late intervention with anti-NSP4 antibody could halt diarrhea progression in mice.
Our findings demonstrate for the first time that administration of anti-NSP4 antibody is effective both prior to and during the time course of rotavirus infection. These observations extend our knowledge of rotavirus infection and its therapeutic options.
轮状病毒感染是全球儿童感染性腹泻和肠胃炎的最常见病因。病毒蛋白(VP),尤其是由VP4和VP7诱导产生的中和抗体,被认为在轮状病毒疾病的保护性免疫中起关键作用。然而,抗轮状病毒非结构蛋白4(NSP4)抗体是否能直接预防轮状病毒引起的腹泻尚不完全清楚,尤其是其保护时间进程。
为获得直接证据,用NSP4和完整轮状病毒处理12日龄的ICR小鼠以诱导腹泻。
NSP4处理组和轮状病毒处理组小鼠均出现腹泻,与年龄匹配的对照小鼠相比,小肠出现组织学变化。抗NSP4抗体对完整轮状病毒诱导的腹泻和NSP4诱导的腹泻均有保护作用。小肠的组织学变化是可逆的。这些数据表明,早期用抗NSP4抗体干预可预防小鼠轮状病毒诱导的腹泻;晚期用抗NSP4抗体干预可阻止小鼠腹泻进展。
我们的研究结果首次证明,在轮状病毒感染的病程之前及期间给予抗NSP4抗体均有效。这些观察结果扩展了我们对轮状病毒感染及其治疗选择的认识。