Mmupv1 Case Study

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Introduction to the resubmission of R21 AI128282-01 HU, JIAFEN; CHRISTENSEN, NEIL
We thank the Reviewers for their positive comments for our choice of model system as well as for their thoughtful comments, perspectives, and constructive suggestions to improve our proposal. The reviewers agreed that “This (model) is a good application that addresses a problem of high importance in the field”, and “Understanding the innate immune response against the pathogen will generate important information against this sexually transmitted disease which may provide insights into the Infections which fall in this category.” The reviewers, however, raised some concerns that may not have been appropriately addressed in the original proposal including “All three aims are descriptive in nature and hypotheses lack specificity”. We agree with the reviewers that our previous aims were too broad and descriptive because we had not yet obtained sufficient preliminary data to guide our directions at the time. Since the submission of the original proposal, we have made significant progress and generated new data to address
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We demonstrated that both MmuPV1 E6 and E7 are oncogenic in vitro and in vivo (Preliminary Data). We have also constructed several MmuPV1 mutants (E3ATGko, L1ATGko, L2ATGko and L1+L2ATGKo, E6 and E7 codon modified genomes) that showed different phenotypes in vivo (manuscripts in preparation). In addition, we have developed an in vitro assay system to quantitate viral infectivity and neutralizing activity. Although we cannot test vaccines in the nude mice, we can test passive immunization (both humoral and T-cell associated immunity) strategies. Most excitingly, we demonstrated mucosal infection in immunocompetent mice (NU/J Foxn1+/-). We will verify the MmuPV1 infection in the Foxn1+/- of other genetic backgrounds in the revised specific aim

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