In vivo longitudinal imaging of experimental human papillomavirus infection in mice with a multicolor fluorescence mini-endoscopy system.
In vivo longitudinal imaging of experimental human papillomavirus infection in mice with a multicolor fluorescence mini-endoscopy system.
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DOI：
10.1158/1940-6207.capr-10-0334
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Kobayashi H
中科院分区：
文献类型：
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作者：
Mitsunaga M;Kosaka N;Kines RC;Roberts JN;Lowy DR;Schiller JT;Ishihara Y;Hasegawa A;Choyke PL;Kobayashi H
人乳头瘤病毒（HPV）是最常见的性传播感染。HPV感染的疫苗可以降低宫颈癌的风险。为了进一步改进这些疫苗并探索预防或治疗病毒感染的其他方法，需要在实验动物中进行纵向研究。在这里，我们描述了一种新开发的多色内窥镜荧光成像系统，以可视化早期HPV感染与荧光蛋白编码的假病毒（PsV）在活小鼠的雌性生殖道。通过这种成像方法，可以在一只小鼠中随着时间的推移监测HPV PsV感染的过程以及预防感染的干预效果。用阴道杀精剂预处理雌性免疫活性小鼠或无胸腺小鼠，然后阴道内滴注含有真实病毒衣壳和包被的绿色或红色荧光蛋白（GFP或RFP）报告基因的HPV PsV。在PsV攻击后1天检测到GFP或RFP的表达，并在2或3天后达到峰值，此后下降。在疫苗处理的免疫活性小鼠中未检测到荧光。通过使用编码GFP或RFP的相同PsV类型（HPV 16）的连续感染，可以监测重复暴露的不同感染模式。这种方法提供了在干预前后监测实验性病毒感染的能力，从而加速了适当预防和治疗的发展。
Human papillomavirus (HPV) is the most common sexually transmitted infection. Vaccines for HPV infection can reduce the risk of cervical cancer. To further improve such vaccines and to explore other methods of preventing or treating viral infection, longitudinal studies in experimental animals are desirable. Here, we describe a newly-developed multi-color endoscopic fluorescence imaging system to visualize early HPV infection with fluorescent protein-encoded pseudoviruses (PsV) in the female genital tract of living mice. With this imaging method, the course of HPV PsV infection, and the effects of intervention to prevent infection can be monitored in a single mouse over time. Female immunocompetent or athymic mice were pretreated with a vaginal spermicide, and then HPV PsV containing an authentic viral capsid and encapsidating green or red fluorescent protein (GFP or RFP) reporter gene was intravaginally instilled. Expression of GFP or RFP was detected 1 day after PsV challenge, and peaked after 2 or 3 days, decreasing thereafter. No fluorescence was detected in vaccine-treated immunocompetent mice. By using serial infection of the same PsV type (HPV 16) encoding either GFP or RFP, different infection patterns of repeated exposure can be monitored. This method offers the ability to monitor experimental virus infections before and after intervention thereby accelerating the development of appropriate prevention and therapy.