title: Tracking vaginal, anal and oral infection in a mouse  papillomavirus infection model.
abstract: 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.
authors.affiliation: The Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.|Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Jiafen
authors.initials: J
authors.lastname: Hu
authors.affiliation: The Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.|Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Budgeon
authors.affiliation: The Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.|Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Cladel
authors.affiliation: The Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.|Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Karla
authors.initials: K
authors.lastname: Balogh
authors.affiliation: Section of Research Resources, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Myers
authors.affiliation: Department of Comparative Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Cooper
authors.affiliation: Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.|The Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.|Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Christensen
mesh_terms: D001003:Anal Canal / Q000473:pathology / Q000821:virology*; D000818:Animals; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology*; D056915:DNA Copy Number Variations / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009055:Mouth / Q000473:pathology / Q000821:virology*; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000821:virology*; D014621:Vagina / Q000473:pathology / Q000821:virology*
chemical_list: D004279:DNA, Viral