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Papillomaviruses (PVs) are double stranded (ds)-DNA viruses (~8-kbp), which infect mucosal and cutaneous epithelial cells from various mammalian species, causing tumors in both epithelial cell-types. During the late-phase, the capsid proteins (L1 and L2), are expressed to encapsidate the viral genome generating infectious virion particles required for PV. Natural PV infections produce morphologically homogenous progeny virions 55-nm in diameter. Transient transfection systems allow individual expression of the capsid proteins, which are able to produce low-levels of infectious virion-like particles (VLPs) and non-infectious VLPs that have the capacity to resemble and function as wild-type virions.
Results: The research herein demonstrates the conserved sequence homology amongst the variety of PV L2 proteins reveals its necessity and conserved role during PV infections. The L1 and L2 DNA-binding domains were bioinformatically analyzed and the results showed amino acid sequence homology amongst all PV genera. The L2 DNA-BDs have sequence homology in comparison to the DNA-binding proteins from three species within the Microviridae family (ex. φX174, alpha-3). Previously, reports demonstrate the L2 protein interacting with the PV encoded E2, trans-regulatory, protein. The studies herein discover a novel interaction between the E2 and L1 protein of HPV16. The L1-to-E2 interaction is highly dynamic and may be dependent upon the spontaneous oligomerization of the L1 protein. Use of the Cluspro docking software predicts E2 to interact with the BC-loop (49-61 a.a.) and HI-loop (341-362 a.a) of the L1 protein, localized within the valley/cleft of the known pentamer-to-pentamer interactions.
Advisor: Peter Angeletti