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1.A.86 The Human Papilloma Virus type 16 (HPV16) L2 Viroporin (L2 Viroporin) Family

During cellular invasion, human papilloma virus type 16 (HPV16) transfers its viral genome (vDNA) across the endosomal membrane prior to its accumulation at nuclear PML bodies for the establishment of infection. After cellular uptake, the capsid likely undergoes pH-dependent disassembly within the endo-/lysosomal compartment, thereby exposing hidden domains in L2 that facilitate membrane penetration of L2/vDNA complexes. Regions of L2 that physically interact with membranes include residues 45 to 67. In vitro, the predicted TMS adopts an alpha-helical structure in lipid environments and can function as a real TM domain, although not as efficiently as the bona fide TM domain (Bronnimann et al. 2013). An L2 double point mutant renders the TM domain nonfunctional and blocks HPV16 infection by preventing endosomal translocation of vDNA. The TM domain contains three highly conserved GxxxG motifs. These motifs facilitate homotypic and heterotypic interactions between TM helices and are important for vDNA translocation. Disruption of some of these GxxxG motifs resulted in noninfectious viruses. This TMS self-associates for the transfer of vDNA across the endo-/lysosomal membrane (Bronnimann et al., 2013). There is some question as to whether L2 functions as a viroporin.

References associated with 1.A.86 family:

Bronnimann, M.P., J.A. Chapman, C.K. Park, and S.K. Campos. (2013). A transmembrane domain and GxxxG motifs within L2 are essential for papillomavirus infection. J. Virol. 87: 464-473. 23097431
Campos, S.K. (2017). Subcellular Trafficking of the Papillomavirus Genome during Initial Infection: The Remarkable Abilities of Minor Capsid Protein L2. Viruses 9:. 29207511
Demaegd, D., F. Foulquier, A.S. Colinet, L. Gremillon, D. Legrand, P. Mariot, E. Peiter, E. Van Schaftingen, G. Matthijs, and P. Morsomme. (2013). Newly characterized Golgi-localized family of proteins is involved in calcium and pH homeostasis in yeast and human cells. Proc. Natl. Acad. Sci. USA 110: 6859-6864. 23569283
Xie, J., P. Zhang, M. Crite, C.V. Lindsay, and D. DiMaio. (2021). Retromer stabilizes transient membrane insertion of L2 capsid protein during retrograde entry of human papillomavirus. Sci Adv 7:. 34193420