%0 Journal Article
%T Molecular Mechanisms of HPV Infection in the Lower Genital Tract
%A G Adonakis
%A G Decavalas
%A G Androutsopoulos
%J Vaccines and Research (IJVR)
%D 2018
%R http://dx.doi.org/10.19070/2572-7427-140001e
%X Human papillomaviruses (HPV) are small, non-enveloped viruses.[1] They contain circular double-stranded DNA within an icosahedral capsid.[2] Despite their small size, they have very complex molecular biology.[3] They have 2 structural proteins (L1 and L2) that compose the viral capsid.[3-5] Also, they have 3 oncogenes (E5, E6 and E7) that modulate the transformation process.[3,4] Moreover, they have 2 regulatory proteins (E1 andE2) that modulate transcription and replication.[3,4] The infectious cycle of HPV is conducted entirely within a fully differentiated squamous epithelium.[1] HPV infection requiresthat virus particles gain access to the epithelial basal layer and enter the dividing basal cells.[2] It is necessary a micro-abrasion of the epithelial surface, that removes the epithelium but keeps the basement membrane intact.[1] The thinner and more fragile metaplastic epithelium may be more susceptible to the microabrasion process and thus to HPV infection.[1] HPV infection is very common in young sexually active women.[1] The viral L1 protein binds to the exposed basement membrane of probably via heparan sulphate proteoglycans (HSPGs) [primary receptor].[1,6-8] This binding results in conformational changes and distortion of the virus capsid.[1,6-8] This distortion exposes the viral L2 protein to cleavage by furin or by proprotein convertase 5/6.[1,6-10] This cleavage site is absolutely conserved among all HPV types[1,9-11] Proteolytic cleavage by furin, is essential for successful infection.[6,8-11] After cleavage, the viral L2 protein binds to the cell surface and this triggers a second conformational change in the virus capsid. [1,6,11] This conformational change either exposes the binding site for the secondary receptor on the viral L1 protein or it lowers the affinity for the primary receptor.[1,6,8,10,11] Then viral L1 protein binds to ¦Á6 integrin on the cell surface [secondary receptor] and triggers receptor mediated endocytosis of HPV. [1,6,7,10,11] Most HPV types generally use clathrin dependent endocytic pathway.[6,8,10-13] However, some HPV types use alternative endocytic pathways (caveolae dependent endocytic pathway or clathrin and caveolae independent endocytic pathway).[6,8,10,11,14,15] HPV has the ability to avoid lysosomal degradation.[13-16] It can escape from the endosomes to the cytosol, with fusion independent mechanisms.[16] The decrease of pH in early endosomes results in conformational changes of HPV capsid and trigger the endosomal escape of the HPV genome or the complex of HPV genome and L2 protein.[13,17] Viral L2
%K n/a
%U https://scidoc.org/IJVR-2572-7427-01-001e.php