(C) APPROACH We propose to test the hypothesis that papillomavirus infection and persistence are influenced by local host defense factors. MmuPV1 persistent infection at mucosal sites in outbred and inbred nude mice can be tracked (15-17) in addition to skin sites (35)(Preliminary data). Interestingly, not all sites showed the same level of susceptibility to MmuPV1 infection. For example, the back skin has been the least susceptible site when compared with other skin sites such as the tail and the muzzle. The vaginal tract is the most susceptible site when compared with the other mucosal sites such as oral and anal sites (16, 17, 34, 36). To obtain the robust and unbiased results, we will include up to six samples (3-4 samples are commonly used for this kind of study) of each group for RNA sequencing. To minimize the variables in the study, we plan to use the inbred mouse strain (NU/J-Foxn1nu/J). To minimize the variation in age, the siblings of the infected mice without infection will be used as negative controls. In Specific …show more content…
Both outbred and inbred nude mice are susceptible to MmuPV1 infection at different cutaneous sites. MmuPV1 infection was initiated at cutaneous sites including the muzzle, the tail, and the back. The lesions on the tail appear earlier than those at the muzzle. When compared with muzzle and tail sites, the back is the least susceptible site. Interestingly, secondary back skin infection can be found in many animals that were initially infected at mucosal sites indicating a self-infection was efficient to grow tumors in nude mice. A carcinoma was developed in a female outbred nude mouse skin site A cutaneous lesion grew at the foreleg of one infected animal at 9.5 months post-infection (Fig. 2A). Histological analysis showed that this lesion had progressed to malignancy (Fig. 2B). The lesion was MmuPV1 positive (Fig. 2