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The Role of the HPV L2 C-terminus Cationic Region in Endosomal Membrane Destabilization and vDNA Trafficking

Advait Jeevanandam, Shuaizhi Li, and Dr. Samuel K. Campos, Department of Immunobiology, The University of Arizona, BIO5 institute, 1657 E Helen St, Tucson, AZ 85719

Human Papillomavirus (HPV) is a common STI and the cause of ~99% of cervical cancers. The virion capsid is composed of L1 major capsid protein and L2 minor capsid protein. A wound permits HPV entry, via endocytosis, into the basal keratinocytes of the skin or oral/genital mucosa, and the majority of L1 is degraded in the acidic environment of the endosome, exposing the L2-vDNA complex. Previous studies show the L2 C-terminus cationic region is essential for destabilization and spanning across the endosomal membrane, enabling L2 to bind to cytosolic retromer. This begins the retrograde trafficking of the L2-vDNA complex to the Trans-Golgi network (TGN)— a required step for HPV infection before it translocates to the nucleus. However, how L2 is associated with and transports vDNA is unknown, and we hypothesize that the L2 cationic region can not only aid in destabilizing the endosome membrane, but can also play an important role in interacting with the anionic vDNA. To delineate the potential roles of L2 in vDNA binding/trafficking, we mutated the L2 C-terminus to alter the membrane destabilizing and/or vDNA binding ability. An important mutant named ASAQAT has alternating nonpolar and polar residues, and immunofluorescence data indicates L2 reaches the nucleus in similar amounts to wildtype L2 virus, but infection data shows 25% less infection, implying L2 ASAQAT can protrude and access retromer to leave the endosome, but is unable to complex with vDNA, suggesting the L2 cationic region is possibly just as important for vDNA transport. Fluorophore-conjugated synthetic peptides of the L2 C-terminus are being synthesized to further understand the roles of L2 as well. Unraveling the molecular details of L2 will broaden our understanding of protein-membrane interactions, HPV subcellular trafficking, and have the potential for the development of specific antivirals, or therapeutics.

 

 




Additional Abstract Information

Presenter: Advait Jeevanandam

Institution: University of Arizona

Type: Poster

Subject: Microbiology

Status: Approved


Time and Location

Session: Poster 8
Date/Time: Tue 5:00pm-6:00pm
Session Number: 5633