Tracking vaginal, anal and oral infection in a mouse papillomavirus infection model

Noninvasive and practical techniques to longitudinally track viral infection are sought after in clinical practice. We report a proof-of-principle study to monitor the viral DNA copy number using a newly established mouse papillomavirus (MmuPV1) mucosal infection model. We hypothesized that viral pr...

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Bibliographic Details
Published in:Journal of general virology 2015-12, Vol.96 (12), p.3554-3565
Main Authors: Hu, Jiafen, Budgeon, Lynn R, Cladel, Nancy M, Balogh, Karla, Myers, Roland, Cooper, Timothy K, Christensen, Neil D
Format: Article
Language:English
Subjects:
Anal Canal - pathology
Anal Canal - virology
Animals
Cervix Uteri - pathology
Cervix Uteri - virology
Disease Models, Animal
DNA Copy Number Variations - genetics
DNA, Viral - genetics
Female
Mice
Mice, Nude
Mouth - pathology
Mouth - virology
Papillomaviridae - physiology
Papillomavirus Infections - virology
Vagina - pathology
Vagina - virology
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Summary:Noninvasive and practical techniques to longitudinally track viral infection are sought after in clinical practice. We report a proof-of-principle study to monitor the viral DNA copy number using a newly established mouse papillomavirus (MmuPV1) mucosal infection model. We hypothesized that viral presence could be identified and quantified by collecting lavage samples from cervicovaginal, anal and oral sites. Nude mice infected at these sites with infectious MmuPV1 were tracked for up to 23 weeks starting at 6 weeks post-infection. Viral DNA copy number was determined by SYBR Green Q-PCR analysis. In addition, we tracked viral DNA load through three complete oestrous cycles to pinpoint whether there was a correlation between the DNA load and the four stages of the oestrous cycle. Our results showed that high viral DNA copy number was reproducibly detected from both anal and cervicovaginal lavage samples. The infection and disease progression were further confirmed by histology, cytology, in situ hybridization, immunohistochemistry and transmission electron microscopy. Interestingly, the viral copy number fluctuated over the oestrous cycle, with the highest level at the oestrus stage, implying that multiple sampling might be necessary to provide a reliable diagnosis. Virus DNA was detected in oral lavage samples at a later time after infection. Lower viral DNA load was found in oral samples when compared with those in anal and vaginal tracts. To our knowledge, our study is the first in vivo study to sequentially monitor papillomavirus infection from mucosal anal, oral and vaginal tracts in a preclinical model.
ISSN:0022-1317
1465-2099
DOI:10.1099/jgv.0.000295