A high-dose inoculum size results in persistent viral infection and arthritis in mice infected with chikungunya virus.
A high-dose inoculum size results in persistent viral infection and arthritis in mice infected with chikungunya virus.
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高剂量接种量会导致感染基孔肯雅病毒的小鼠出现持续性病毒感染和关节炎。
DOI：
10.1371/journal.pntd.0010149
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发表时间：
2022-01
影响因子：
3.8
通讯作者：
Yan H
中科院分区：
文献类型：
--
作者：
Zhang Y;Yan H;Li X;Zhou D;Zhong M;Yang J;Zhao B;Fan X;Fan J;Shu J;Lu M;Jin X;Zhang E;Yan H
基孔肯雅病毒（CHIKV）是一种新出现的蚊子传播的甲病毒，可导致急性发热和慢性衰弱性多关节痛。迄今为止，慢性复发性关节痛的机制尚不清楚。在本研究中，新生野生型C57 BL/6小鼠感染CHIKV，并在50天内分析CHIKV感染的病毒学和病理学特征。通过以10空斑形成单位（PFU）至106 PFU的剂量范围的CHIKV的足垫接种容易地建立急性病毒感染，在此期间，在足组织中检测到接种剂量依赖性病毒RNA和骨骼肌损伤。然而，只有当小鼠感染高剂量106 PFU的CHIKV时，才观察到持续的CHIKV，其中从29至50 dpi在足部连续可检测到低拷贝数（103 - 104）的病毒正链RNA，沿着出现病毒特异性CD 8 + T细胞应答的低水平和进行性降低。相反，病毒负链RNA在50 dpi时检测到，但在29 dpi时未检测到，并且在50 dpi时伴随着显著的局部骨骼肌损伤，此时足关节中出现轻度滑膜增生，尽管损伤在29 dpi时短暂修复。这些结果表明，高病毒接种剂量导致病毒持续存在，并在急性感染恢复后进展为慢性组织损伤。总之，这些结果为阐明持续CHIKV感染和病毒复发相关慢性关节炎的发病机制提供了有用的工具。自1952年病毒最初被分离以来，CHIKV感染已引起几次暴发，并影响了流行地区的数百万人。CHIKV由蚊子传播，导致急性疾病，其典型特征为严重和使人衰弱的关节炎、肌痛和发热，随后是持续或复发的关节和肌肉疼痛，可能持续数月至数年。CHIKV在患者中的持续性已通过临床证据得到验证，但仍不清楚慢性和复发性组织损伤与持续性病毒感染的相关性。在这项研究中，我们在不同病毒接种剂量的小鼠中建立了急性和慢性CHIKV感染，并确定了感染剂量与CHIKV感染结果的相关性。我们发现，高剂量接种不仅导致持续的病毒感染，而且导致小鼠肌炎和关节损伤的典型急性-恢复-复发模型。我们还发现CHIKV RNA复制在急性期后中断，这可能与抗病毒T细胞应答低和组织病理损伤复发有关。我们的研究强调了CHIKV感染后临床结局的关键因素，并为病毒持续存在和复发性关节炎之间的相互作用提供了新的见解。
Chikungunya virus (CHIKV) is an emerging mosquito-transmitted alphavirus that leads to acute fever and chronic debilitating polyarthralgia. To date, the mechanism underlying chronic recurrent arthralgia is unknown. In the present study, newborn wild-type C57BL/6 mice were infected with CHIKV, and the virological and pathological features of CHIKV infection were analyzed over a period of 50 days. Acute viral infection was readily established by footpad inoculation of CHIKV at doses ranging from 10 plaque forming unit (PFU) to 106 PFU, during which inoculation dose-dependent viral RNA and skeletal muscle damage were detected in the foot tissues. However, persistent CHIKV was observed only when the mice were infected with a high dose of 106 PFU of CHIKV, in which low copy numbers (103−104) of viral positive strand RNA were continuously detectable in the feet from 29 to 50 dpi, along with a low level and progressive reduction in virus-specific CD8+ T cell responses. In contrast, viral negative strand RNA was detected at 50 dpi but not at 29 dpi and was accompanied by significant local skeletal muscle damage at 50 dpi when mild synovial hyperplasia appeared in the foot joints, although the damage was briefly repaired at 29 dpi. These results demonstrated that a high viral inoculation dose leads to viral persistence and progression to chronic tissue damage after recovery from acute infection. Taken together, these results provide a useful tool for elucidating the pathogenesis of persistent CHIKV infection and viral relapse-associated chronic arthritis. CHIKV infection has caused several outbreaks and affected millions of people in epidemic areas since the virus was originally isolated in 1952. CHIKV is transmitted by mosquitoes, resulting in acute diseases typically characterized by severe and debilitating arthritis, myalgia and fever, followed by persistent or recurrent joint and muscle pain that may last for months to years. The persistence of CHIKV in patients has been validated by clinical evidence, but it remains unclear how chronic and recurrent tissue injury are correlated with persistent viral infection. In this study, we established acute and chronic CHIKV infections in mice with different viral inoculation doses and identified the correlation of infection dose with outcomes resulting from CHIKV infection. We found that a high inoculation dose not only resulted in persistent viral infection but also led to a typical acute-recovery-relapse model of myositis and joint injury in mice. We also found that CHIKV RNA replication was interrupted after the acute phase, which might be related to the low antiviral T cell responses and relapse of histopathological injuries. Our study highlights the key factors involved in the clinical outcomes after CHIKV infection and provides new insights into the interaction between viral persistence and recurrent arthritis.
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使用 eGFP 基孔肯雅病毒开发中和测定法
DOI：
10.3390/v8070181
发表时间：
2016-06-28
期刊：
Viruses
影响因子：
--
作者：
Deng CL;Liu SQ;Zhou DG;Xu LL;Li XD;Zhang PT;Li PH;Ye HQ;Wei HP;Yuan ZM;Qin CF;Zhang B
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Zhang B
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发表时间：
2006-01-01
影响因子：
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