Bopegamage Shubhada, Kovacova Jana, Vargova Agnesa, Motusova Jana, Petrovicova Anna, Benkovicova Maria, Gomolcak Pavol, Bakkers Judith, van Kuppeveld Frank, Melchers Willem J G, Galama Jochem M
Department of Virology, Slovak Medical University, Limbova 12, 83303 Bratislava, Slovak Republic.
Institute of Pathology, Derer's Hospital and Clinic, Limbova 5, 83301 Bratislava, Slovak Republic.
J Gen Virol. 2005 Dec;86(Pt 12):3271-3280. doi: 10.1099/vir.0.81249-0.
The pathogenesis of coxsackie B virus (CVB) infections is generally studied in mice by intraperitoneal (i.p.) injection, whereas the gastrointestinal tract is the natural porte d'entrée in humans. The present study was undertaken to compare systematically the influence of infection route on morbidity and pathology. Swiss Albino mice were infected with CVB3 (Nancy) at different doses (5 x 10(3), 5 x 10(5), 5 x 10(7), 5 x 10(9) TCID50), given either i.p. or orally. Virus could be isolated from several organs (heart, spleen and pancreas), indicating systemic infection, irrespective of the infection route. Virus titres were 1-2 logs higher after i.p. infection, but kinetics were largely independent of infection route. Organs became negative for virus isolation after 21 days, with the exception of spleen tissue, which remained positive for up to 49 days. Thereafter, virus was detected only by immunohistochemistry and PCR up to 98 days post-infection (oral route). Histopathology showed mild inflammation and necrosis in heart tissue of all mice during the acute phase, with repair at later stages. Strikingly, pancreatic lesions were confined to the exocrine pancreas and observed only after i.p. infection. Under all experimental conditions, the pancreatic islets were spared. In contrast, immunohistochemistry showed the presence of viral VP1, protein 3A and alpha interferon (IFN-alpha) in exocrine as well as endocrine pancreas of all mice, irrespective of route and dose of infection. It is concluded that infection via the oral route protects the pancreas from damage, but not from infection, a process in which IFN-alpha is not the only factor involved.
柯萨奇B病毒（CVB）感染的发病机制通常通过腹腔内（i.p.）注射在小鼠中进行研究，而胃肠道是人类的天然入口。本研究旨在系统比较感染途径对发病率和病理学的影响。将不同剂量（5×10³、5×10⁵、5×10⁷、5×10⁹ TCID50）的CVB3（Nancy）通过腹腔内注射或口服的方式感染瑞士白化小鼠。无论感染途径如何，均可从多个器官（心脏、脾脏和胰腺）分离出病毒，表明存在全身感染。腹腔内感染后病毒滴度高1-2个对数，但动力学在很大程度上与感染途径无关。21天后各器官病毒分离呈阴性，但脾脏组织除外，其在长达49天内仍呈阳性。此后，在感染后98天（口服途径）之前，仅通过免疫组织化学和PCR检测到病毒。组织病理学显示，在急性期所有小鼠的心脏组织均有轻度炎症和坏死，后期有修复。令人惊讶的是，胰腺病变仅限于外分泌胰腺，且仅在腹腔内感染后观察到。在所有实验条件下，胰岛均未受累。相比之下，免疫组织化学显示，无论感染途径和剂量如何，所有小鼠的外分泌胰腺和内分泌胰腺中均存在病毒VP1、蛋白3A和α干扰素（IFN-α）。得出的结论是，经口感染可保护胰腺免受损伤，但不能防止感染，在这一过程中，IFN-α不是唯一涉及的因素。
