Verruca

Megan Shanzu (2017 060 10127)

The genome of HPV consists of early genes (E1, E2, E4, E6 and E7), two
late genes (L1 and L2 ) and in between an upstream regulatory region (URR). L1 and
L2 code or the major or and minor capsid proteins. L1 encodes for the major capsid
protein and sel assembles into viruslike particles (VLPs). The L2 gene encodes the
minor capsid protein and has at least two important functions. L2 protein helps expose
the keratinocyte binding determinant of the L1 protein, allowing for the HPV to bind
onto the basal keratinocyte and to be taken into the cell.1

HPV infection occurs through inoculation of virus into the viable epidermis
through breaks in the epithelial barrier. In rodent models of cervical HPV infection,
mechanical disruption of the epithelium or inclusion of the mild detergent nonoxynol-
9 dramatically increased the incidence of infection. Animal models using HPV virions
demonstrate that attachment to heparan sulfate proteoglycans on the basement
membrane is a required initial step in natural infection. A furin protease then cleaves
L2, inducing a conformation change that allows binding to an unidentifed basal cell
receptor. This experimental model explains how PVs reserve infection for and
specifically target epithelial basal cells.2

The HPV life cycle is closely linked to epithelial differentiation of skin

keratinocytes, with initial infection occurring only in the undifferentiated proliferating
basal compartment of the epithelium and progeny virus production only in the
terminally differentiated suprabasal compartment.3

Papillomavirions gain entry into basal cells through a wound or microlesion.

Active HPV infections stimulate cell cycling and increase the thickness of the
parabasal and spinous strata, resulting in warty growth.4

To establish persistent infection, the virus presumably must enter a stem cell
or one with stem-like properties. After entry, a single copy or at most a few copies of
the viral genome are maintained as an extrachromosomal plasmid or episome within
the infected epithelial basal cell’s nucleus. When these cells divide, the viral genome
also replicates and partitions to the progeny cell, which transports the viral infection
into the differentiating layers of the epithelium. Viral RNA expression (transcription)
is extremely low until the upper Malpighian layer, where viral DNA synthesis and
genome amplication typically results in hundreds to thousands of copies per cell The
newly synthesized viral DNA is packaged in the capsid, and mature virions
accumulate in the nuclei of these upper level cells. The viral E1-E4 protein may
induce collapse of the cytoplasmic keratin lament network that surrounds the residual
nucleus that contains assembled viruses. This is postulated to facilitate release of the
virions from the cross-linked cytoskeleton of keratinocytes/corneocytes so that virus
can be inoculated into another site or desquamated into the environment.2
 Fig 1. Schematic representation of the HPV life cycle in the context of a
differentiating epithelium.5

Sources:

1. James WD, Berger TG, Elston DM. Andrews’ Disease of the Skin Clinical
Dermatology. 12th ed. Elsevier. 2016.

2. Lapeere H, Boone B, Schepper SD, Verhaeghe E, Gele MV, Ongenae K, et al.

Fitzpatrick’s Dermatology in General Medicine. 8th ed. New York: Mc Graw
Hill. 2012.

3. Establishment of Human Papillomavirus Infection Requires Cell Cycle

Progression [Internet]. [cited 2018 Dec 26]. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642596/

4. Human Papillomavirus Infections: Warts or Cancer? [Internet]. [cited 2018 Dec

26]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685896/

5. Molecular Mechanisms of Human Papillomavirus-Induced Carcinogenesis

[Internet]. [cited 2018 Dec 26]. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654617/