Large Amounts of Reactivated Virus in Tears Precedes Recurrent Herpes Stromal Keratitis in Stressed Rabbits Latently Infected with Herpes Simplex Virus.
Large Amounts of Reactivated Virus in Tears Precedes Recurrent Herpes Stromal Keratitis in Stressed Rabbits Latently Infected with Herpes Simplex Virus.
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DOI：
10.3109/02713683.2015.1020172
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发表时间：
2016
影响因子：
2
通讯作者：
Wechsler SL
中科院分区：
文献类型：
--
作者：
Perng GC;Osorio N;Jiang X;Geertsema R;Hsiang C;Brown D;BenMohamed L;Wechsler SL
复发性单纯疱疹性角膜基质炎（rHSK），由于对单纯疱疹病毒（HSV-1）再活化的免疫反应，可导致角膜失明。由于缺乏一种小型可靠的动物模型，其中rHSK在HSV-1潜伏期内以高频率发生，因此开发药物和疫苗等治疗干预措施以减少rHSK受到阻碍。本研究的目的是建立一种rHSK兔模型，其中高温应激增加了HSV-1再激活和rHSK的频率。将潜伏感染HSV-1的家兔置于高温下，测定病毒再活化和rHSK的频率。在一项实验中，由于动物园空调系统的故障，潜伏感染HSV-1的兔子受到不明确的应激，HSV-1的再激活发生在正常频率的两倍以上。此外，60%的眼睛发展为严重的rHSK，而正常情况下只有1%。所有rHSK发作前4 - 5天，该眼泪液中存在异常大量的再活化病毒，每当在泪液中检测到这种异常大量的再活化病毒时，rHSK总是在4-5天后出现。在随后的实验中，使用定义明确的热应激的再激活频率同样增加，但没有眼睛发展rHSK。本文报道的结果支持了以下假设：rHSK不仅与再激活频率升高有关，而且与4-5天前泪液中极高水平的再激活病毒的罕见事件有关。
Recurrent herpetic stromal keratitis (rHSK), due to an immune response to reactivation of herpes simplex virus (HSV-1), can cause corneal blindness. The development of therapeutic interventions such as drugs and vaccines to decrease rHSK have been hampered by the lack of a small and reliable animal model in which rHSK occurs at a high frequency during HSV-1 latency. The aim of this study is to develop a rabbit model of rHSK in which stress from elevated temperatures increases the frequency of HSV-1 reactivations and rHSK. Rabbits latently infected with HSV-1 were subjected to elevated temperatures and the frequency of viral reactivations and rHSK were determined. In an experiment in which rabbits latently infected with HSV-1 were subjected to ill-defined stress as a result of failure of the vivarium air conditioning system, reactivation of HSV-1 occurred at over twice the normal frequency. In addition, 60% of eyes developed severe rHSK compared to <1% of eyes normally. All episodes of rHSK were preceded four to five days prior by an unusually large amount of reactivated virus in the tears of that eye and whenever this unusually large amount of reactivated virus was detected in tears, rHSK always appeared 4–5 days later. In subsequent experiments using well defined heat stress the reactivation frequency was similarly increased, but no eyes developed rHSK. The results reported here support the hypothesis that rHSK is associated not simply with elevated reactivation frequency, but rather with rare episodes of very high levels of reactivated virus in tears 4–5 days earlier.