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Proprotein Convertase Selectivity in the Activation of the Human Papilloma Virus
Author(s) -
Izaguirre Gonzalo
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb106
Subject(s) - furin , proprotein convertase , cleavage (geology) , proprotein convertases , secretion , tropism , virus , biology , virology , serine , gene , proteases , microbiology and biotechnology , genetics , biochemistry , phosphorylation , enzyme , lipoprotein , paleontology , ldl receptor , cholesterol , fracture (geology)
The family of host cell serine proteinases known as proprotein convertases (PCs) is exploited by a variety of human pathogenic viruses to promote viral activation. The PCs, furin, PC5, PACE4, and PC7 reside in the trans‐Golgi network membranes of the constitutive secretion pathway and are expressed in most human tissues. We study PC selectivity for the activation of the human papilloma virus (HPV), and for that purpose we applied an approach that combines the use of recombinant PCs and an assay of HPV cell entry. We found differences in PC selectivity between HPV genotypes 16 and 18 for activation by furin, PACE4, and PC7, and showed that both viral genotypes are inactivated by PC5. These findings imply that proteolytic cleavage of the coat proteins in these two high cancer‐risk HPV genotypes involves multiple cleavage sites with different PC specificity, and challenge the current accepted model of HPV cell entry that postulates that only one PC cleavage site, located on the coat protein L2 at position Arg12, is needed for viral activation. The inactivation by mutagenesis of the six potential PC cleavage site motifs in HPV16, two in L1 and four in L2, demonstrated that additional PC cleavage sites in L1 and L2 are required for HPV16 infection. These results suggest that PC selectivity could be a determinant of viral tropism to anatomical sites of infection based on tissue PC expression profile.