This study used the rodent latently infected with papillomavirus (MnPV) and PV2 (McPV2), which induce skin papillomas and anogenital condylomas, respectively, to investigate PV antibody responses as serological markers during pathogenesis. In a case–control study (137 animals), virus and tumour prevalence correlated with the seroresponse against the early E2 and late L1 viral proteins. A prospective study (53 animals) revealed for the first time the course of these antibody responses during all stages of a natural PV infection. Numerous tumour entities were observed on the eyelid and in the oral cavity. DNA analyses indicated that McPV2 was not restricted to condylomas but was also present in these mucosa-associated papillomas. The serological survey using a recently established glutathione -transferase-capture ELISA detected a strong correlation between MnPV L1-specific antibodies and the presence of papillomas on the skin, eye and ear (<0.001). Notably, extensive antibody responses to MnPV E2 were also detected in these cases. A prospective study revealed that E2 reactivity occurred by the age of 1 month. MnPV L1 antibodies were found at 2.5 months, indicating the initiation of productive viral infection. Thirty-one out of 34 L1-seropositive animals at the age of 4.5 months developed MnPV-associated tumours (positive predictive value=77 %), and none of the seronegative animals developed skin papillomas (negative predictive value=100 %). MnPV E2 and L1 serology thus provides a powerful tool for monitoring early infection and skin tumour progression in .


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