Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
Antiviral Res. 2010 May;86(2):188-95. doi: 10.1016/j.antiviral.2010.02.317. Epub 2010 Feb 16.
A mouse model of recurrent herpes simplex type 2 (HSV-2) would improve our understanding of the immunobiology of recurrent disease and provide a useful model for evaluating antiviral treatments. We developed a model to evaluate recurrent vaginal HSV-2 shedding using high-dose acyclovir (ACV) therapy beginning at 3 days post infection (dpi). Treatment with 150mg/kg of ACV for 10 days increased survival to 80% following vaginal challenge with HSV-2 strain 186 and to 100% after challenge with strain MS. We then evaluated recurrent vaginal HSV-2 shedding in surviving mice. Although infectious virus was not detected in vaginal samples after 21dpi, viral DNA was detectable by PCR in 80% of mice (47/59) on at least 1 day, while no animal was positive for virus on every day. ACV therapy administered from day 21 to 31 significantly reduced recurrent virus shedding during this period from 7.3% (8/109 swabs) to 0.8% (1/126 swabs) (p=0.013). Lastly, ACV-rescued HSV-2-infected mice treated with cyclophosphamide at 35 and 38dpi rapidly succumbed, indicating that this model can be used to study immune control of the persistent infection. Thus, this model provides an inexpensive model for evaluating therapeutic strategies and immune control of persistent HSV.
一种复发性单纯疱疹病毒 2 型（HSV-2）的小鼠模型将有助于我们了解复发性疾病的免疫生物学，并为评估抗病毒治疗提供有用的模型。我们开发了一种模型，通过在感染后 3 天（dpi）开始使用高剂量阿昔洛韦（ACV）治疗来评估复发性阴道 HSV-2 脱落。用 150mg/kg 的 ACV 治疗 10 天，可使阴道感染 HSV-2 186 株的小鼠存活率提高到 80%，感染 MS 株的小鼠存活率提高到 100%。然后，我们评估了幸存小鼠的复发性阴道 HSV-2 脱落。尽管在 21dpi 后阴道样本中未检测到传染性病毒，但在至少 1 天的时间内，80%（47/59）的小鼠通过 PCR 可检测到病毒 DNA，而没有动物每天都呈阳性。从第 21 天到第 31 天用 ACV 治疗可使这段时间的复发性病毒脱落从 7.3%（8/109 个拭子）减少到 0.8%（1/126 个拭子）（p=0.013）。最后，在 35 和 38dpi 用环磷酰胺治疗被 ACV 挽救的 HSV-2 感染的小鼠迅速死亡，表明该模型可用于研究对持续性感染的免疫控制。因此，该模型为评估持续性 HSV 的治疗策略和免疫控制提供了一种廉价的模型。
