Detection of viral DNA and E4 protein in basal keratinocytes of experimental canine oral papillomavirus lesions.
We studied experimental canine oral papillomavirus (COPV) infection by in situ hybridization and immunohistochemistry of weekly biopsies. After 4 weeks, viral DNA in rete ridges suggested a keratinocyte stem cell target. Abundant viral DNA was seen in E4-positive cells only. E4 was predominantly cytoplasmic but also nuclear, being concentrated in the nucleoli during wart formation. Infected cells spread laterally along the basal layer and into the parabasal layers, accompanied by E7 transcription and increased mitoses. Most of the lower epithelium was positive for viral DNA, but, in mature warts, higher levels of E4 expression and genome amplification occurred in only sporadic superficial cells. L1 expression was late and in only a subset of E4-positive cells. During regression, viral DNA was less abundant in deep epithelial layers, suggesting downregulation of replication prior to replacement of infected cells from beneath. Detection of viral DNA in post-regression tissue indicated latent infection.
Nicholls
P K
PK
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, United Kingdom. nicholls@numbat.murdoch.edu.au
Doorbar
J
J
Moore
R A
RA
Peh
W
W
Anderson
D M
DM
Stanley
M A
MA
D000818:Animals; D002213:Capsid / Q000096:biosynthesis; D036022:Capsid Proteins; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000821:virology*; D008940:Mitotic Index; D009059:Mouth Diseases / Q000821:virology*; D009061:Mouth Mucosa / Q000821:virology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000302:isolation & purification*; D016366:Open Reading Frames; D027383:Papillomaviridae / Q000145:classification* / Q000235:genetics / Q000502:physiology; D030361:Papillomavirus Infections / Q000821:virology*; D015347:RNA Probes; D012367:RNA, Viral / Q000737:chemistry; D014412:Tumor Virus Infections / Q000821:virology*; D014764:Viral Proteins; D017735:Virus Latency
D036022:Capsid Proteins; D004279:DNA, Viral; C097166:L1 protein, canine oral papillomavirus; D015514:Oncogene Proteins, Fusion; D015347:RNA Probes; D012367:RNA, Viral; D014764:Viral Proteins; C072777:oncogene protein E1--E4, Human papillomavirus type 16