PATHOGENESIS OF RIFT-VALLEY FEVER VIRUS (RVFV) IN INBRED RATS

PATHOGENESIS OF RIFT-VALLEY FEVER VIRUS (RVFV) IN INBRED RATS
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DOI:
10.1016/0882-4010(87)90126-4
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发表时间:
1987-04-01
影响因子:
3.8
通讯作者:
PETERS, CJ
PETERS, CJ
中科院分区:
医学3区
文献类型:
--
作者:
ANDERSON, GW;SLONE, TW;PETERS, CJ

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本文研究了3个近交系(LEW、MAXX、WF)成年大鼠裂谷热的发病机制。WF大鼠在接种后第2天全部死亡,病毒组织滴度达到9 log 10 PFU/g。LEW和MAXX大鼠对肝脏疾病有抵抗力,但分别有16%和44%的大鼠发生了致命的坏死性脑炎。血清中和抗体的检测在第3天正好从血清和肝脏中清除病毒,虽然感染性病毒检测到脾匀浆中迟至第19天感染后。LEW和MAXX大鼠中的病毒滴度不超过4.5 log 10 PFU/g。环磷酰胺免疫抑制导致LEW大鼠感染后5-9天死亡;病毒复制的早期模式不受影响,但肝脏中的持续生长导致致命性肝炎。这些动物可以通过在感染后第2-5天给予被动抗体治疗来保护,以模拟在未操作的感染LEW大鼠中观察到的血清中和抗体模式。因此,裂谷热病毒在WF大鼠组织中复制和传播迅速,而在LEW和MAXX大鼠中,由于内在机制允许有足够的时间进行免疫反应以终止感染,病毒生长较少。免疫反应的轻微减弱可能导致MAXX大鼠比LEW大鼠更频繁地发生脑炎。这些大鼠品系应有助于阐明限制RVFV诱导的肝炎和脑炎的耐药机制。
The pathogenesis of Rift Valley fever in adult rats from 3 inbred strains (LEW, MAXX, WF) was investigated. WF rats all died by day 2 postinoculation with viral tissue titers reaching 9 log10 PFU/g. LEW and MAXX rats were resistant to liver disease, but fatal necrotising encephalitis developed in 16 and 44% of the rats, respectively. Detection of serum neutralising antibody on day 3 coincided with clearance of virus from serum and liver, although infectious virus was detected in spleen homogenates as late as day 19 postinfection. Viral titers in LEW and MAXX rats did not exceed 4.5 log10 PFU/g. Cyclophosphamide immunosuppression of LEW rats led to death 5-9 days postinfection; early patterns of viral replication were not affected, but continued growth in the liver resulted in fatal hepatitis. These animals could be protected by passive antibody therapy administered on days 2-5 postinfection to mimic the serum neutralising antibody pattern seen in unmanipulated infected LEW rats. Thus, RVF virus replication and spread is rapid in the WF rats tissues, whereas in LEW and MAXX rats viral growth is less due to an intrinsic mechanism which allows sufficient time for an immune response to terminate infection. A slightly diminished immune response may lead to the development of encephalitis more frequently in MAXX than LEW rats. These rat strains should be useful in elucidating those mechanisms of resistance which limit RVFV-induced hepatitis and encephalitis.