Detection of L1, infectious virions and anti-L1 antibody in domestic rabbits infected with cottontail rabbit papillomavirus

Abstract

Shope papillomavirus or cottontail rabbit papillomavirus (CRPV) is one of the first small DNA tumour viruses to be characterized. Although the natural host for CRPV is the cottontail rabbit (Sylvilagus floridanus), CRPV can infect domestic laboratory rabbits (Oryctolagus cuniculus) and induce tumour outgrowth and cancer development. In previous studies, investigators attempted to passage CRPV in domestic rabbits, but achieved very limited success, leading to the suggestion that CRPV infection in domestic rabbits was abortive. The persistence of specific anti-L1 antibody in sera from rabbits infected with either virus or viral DNA led us to revisit the questions as to whether L1 and infectious CRPV can be produced in domestic rabbit tissues. We detected various levels of L1 protein in most papillomas from CRPV-infected rabbits using recently developed monoclonal antibodies. Sensitive in vitro infectivity assays additionally confirmed that extracts from these papillomas were infectious. These studies demonstrated that the CRPV/New Zealand White rabbit model could be used as an in vivo model to study natural virus infection and viral life cycle of CRPV and not be limited to studies on abortive infections.

Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models

“…2 B). Collectively, these findings prove 165 that CRPV circulating in the blood of rabbits can initiate infection at prewounded cutaneous sites, 166 the preferred sites for CRPV infection, and stimulate anti-viral immune responses in these rabbits 167 just as found in local skin infected animals (Hu et al, 2007a). 168…”

Vaccine generated immunity targets an HPV16 E7 HLA-A2.1-restricted CD8+ T cell epitope relocated to an early gene or a late gene of the cottontail rabbit papillomavirus (CRPV) genome in HLA-A2.1 transgenic rabbits

“…Additionally, the CRPV genome can be subjected to a range of PCR-induced mutagenesis events without jeopardizing its functional viability [24]. Finally, our laboratory has shown that domestic rabbits are permissive for CRPV and can be used to study the entire virus life cycle in vivo [29]. These features allowed us to examine the vaccine-induced epitope-specific protective immunity generated against the HLA-A2.1-restricted HPV16E7 82-90 epitope when the epitope is expressed in either a late protein or at the end of an early protein of CRPV.…”

Cottontail Rabbit Papillomavirusin Langerhans Cells inSylvilagusspp.

“…5 Furthermore, CRPV infection has served as a standard in vivo preclinical model for the development of high-risk-type Human papillomavirus (HPV)-induced malignancy in humans. 3,5,12,25 However, there is difficulty in studying the naturally occurring disease in the laboratory as there are limited commercial supplies available of Sylvilagus spp., and this species does not generally adapt well to captivity. 11 Microscopic examination of affected areas revealed multiple papillary masses lined by stratified squamous epithelial cells with central cores of fibrovascular connective tissue arising from the epidermis as well as parakeratotic hyperkeratosis.…”