Pathogenesis of an attenuated and a virulent strain of group A human rotavirus in neonatal gnotobiotic pigs
Pathogenesis of an attenuated and a virulent strain of group A human rotavirus in neonatal gnotobiotic pigs
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DOI：
10.1099/0022-1317-77-7-1431
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发表时间：
1996-07-01
影响因子：
3.8
通讯作者：
Saif, LJ
中科院分区：
文献类型：
--
作者：
Ward, LA;Rosen, BI;Saif, LJ
将在Gn猪（强毒）或细胞培养物（减毒）中连续传代的Wa株（G1 P1 A [P8]）人轮状病毒（Wa HRV）经口接种于Gnn猪，以确定半数病毒感染剂量（ID 50），并评估这两种毒株在Gn猪中诱导的感染部位、形态学病变类型和进展以及临床应答。毒力Wa HRV的ID_（50）≤ 1 f.f.u.而减毒Wa HRV的感染性必须通过血清转化来确定，并且与1.3 × 10（6）f.f.u.相似。接种后13 h（p.i.）在用类似于10（5）f.f.u.的毒性Wa HRV，并与绒毛上皮细胞内的病毒抗原的存在相关;绒毛萎缩发展晚于24小时p.i.并与粪便病毒滴度峰值相关;疾病恢复与形态正常绒毛的恢复相关。在接种类似于2 x 10（8）f.f.u.的猪中未检测到病毒、腹泻和绒毛萎缩。尽管在感染后7天存在HRV特异性血清抗体，但Wa HRV减弱。这些发现表明，毒性Wa HRV感染Gn猪主要发生在肠绒毛上皮细胞与绒毛萎缩发展作为感染的后遗症。然而，绒毛萎缩以外的因素似乎有助于Gn猪中HRV相关疾病表达的早期阶段。减毒病毒在没有疾病或病理的情况下引发病毒中和血清抗体的能力表明将此类毒株用于口服免疫的前景。
Gnotobiotic (Gn) pigs were orally inoculated with Wa strain (G1P1A[P8]) human rotavirus (Wa HRV) serially passaged in Gn pigs (virulent) or cell culture (attenuated) to determine the median virus infectious dose (ID50) and to assess the site of infection and type and progression of morphological lesions and clinical responses induced by these two strains in Gn pigs. The ID50 of virulent Wa HRV was less than or equal to 1 f.f.u. whereas the infectivity of attenuated Wa HRV had to be determined by seroconversion and was similar to 1.3 x 10(6) f.f.u. Diarrhoea developed at 13 h postinoculation (p.i.) in pigs inoculated with similar to 10(5) f.f.u. of virulent Wa HRV and correlated with the presence of viral antigen within villous epithelial cells; villous atrophy developed later at 24 h p.i. and correlated with peak faecal viral titres; recovery from disease correlated with the return of morphologically normal villi. Virus, diarrhoea and villous atrophy were not detected in pigs inoculated with similar to 2 x 10(8) f.f.u. attenuated Wa HRV although HRV-specific serum antibodies were present by 7 days p.i. These findings demonstrate that virulent Wa HRV infection in Gn pigs occurs primarily within intestinal villous epithelial cells with villous atrophy developing as a sequela to infection. However, factors other than villous atrophy appear to contribute to the early stages of HRV-associated disease expression in Gn pigs. The ability of the attenuated virus to elicit virus-neutralizing serum antibodies without disease or pathology indicates promise in the use of such strains for oral immunization.