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Genomic analysis of the first laboratory-mouse papillomavirus
Joongho Joh1, A Bennett Jenson, William King
1James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Abstract:
A papillomavirus (PV) that naturally infects laboratory mice will provide an extremely valuable tool for PV research. We describe here the isolation, cloning and molecular analysis of the first novel laboratory-mouse PV, designated MusPV. This agent, recently identified in the tissues from florid and asymmetrical papillomas on the face of nude mice (NMRI-Foxn1(nu)/Foxn1(nu)), was demonstrated to be transmissible to immunocompetent mice (Ingle et al., 2010). The MusPV genome is 7510 bp in length, is organized similarly to those of other PVs and has at least seven ORFs (E1, E2, E4, E6, E7, L1 and L2). Phylogenetic analysis indicates that MusPV belongs to the π genus together with four other rodent PVs (McPV2, MaPV1, MmiPV and RnPV1). Of the rodent PVs, MusPV appears most closely related to Mastomys coucha PV (McPV2), with 65 % genomic homogeneity and 80 % L1 amino acid similarity. Rodent PVs, except for MnPV1, do not contain any identifiable retinoblastoma protein (RB) binding sites. MusPV has one putative RB-binding site on the E6 protein but not on the E7 protein. Non-coding regions (NCRs) of PVs maintain multiple binding sites for transcription factors (TFs). The NCR of MusPV has numerous sites for TF binding, of which at least 13 TFs are common to all PVs in the π genus. MusPV provides a potentially valuable, novel mouse model to study mechanisms of infection, oncology and novel preventive and therapeutic approaches in mice that can be translated to diseases caused by human PVs.
Insights
A novel papillomavirus (PV), MusPV, was identified in laboratory mice. This discovery offers a valuable new model for studying PV infection, oncology, and developing treatments applicable to human PV diseases.
Area of Science:
- Virology
- Oncology
- Genomics
Background:
- Papillomaviruses (PVs) are significant human pathogens.
- A natural PV model in laboratory mice is crucial for research.
- Previous studies have identified various rodent PVs.
Purpose of the Study:
- To isolate, clone, and characterize the first novel laboratory-mouse PV, named MusPV.
- To analyze the MusPV genome and its phylogenetic relationship with other PVs.
- To evaluate MusPV as a potential model for PV research.
Main Methods:
- Isolation and cloning of MusPV from papillomas in nude mice.
- Molecular analysis of the MusPV genome, including ORF identification.
- Phylogenetic analysis to determine MusPV's relationship to other PVs.
- Identification of retinoblastoma protein (RB) binding sites and transcription factor (TF) binding sites in non-coding regions (NCRs).
Main Results:
- MusPV genome is 7510 bp with seven ORFs (E1, E2, E4, E6, E7, L1, L2).
- MusPV belongs to the π genus, most closely related to Mastomys coucha PV (McPV2).
- MusPV possesses a putative RB-binding site on its E6 protein.
- MusPV's NCR contains numerous TF binding sites, with 13 common to π genus PVs.
Conclusions:
- MusPV is the first identified PV naturally infecting laboratory mice.
- MusPV exhibits genomic organization and phylogenetic characteristics typical of the π genus.
- MusPV serves as a valuable novel mouse model for studying PV infection, oncology, and therapeutic strategies.
- Findings from MusPV research may translate to understanding and treating human PV diseases.
