Poster "The Human Papillomavirus"

The evolutionary history of papillomaviruses seems to coincide with the origin of higher-order vertebrates, amniotes (including reptiles, birds, and mammals) [10]. Mammalian skin structure appears to make them the most suitable hosts for the papillomaviruses [11], and — today — papillomaviruses are widespread in mammals and rarely found in birds. The relationship between papillomaviruses and similar groups of DNA-viruses, such as polyomaviruses, is not well-demonstrated at the present time [12]. There are more than a hundred types of papillomaviruses that can infect humans. These are collectively referred to as human papilloma viruses or HPV and are divided into high-risk (HR) and low-risk (LR) types by their carcinogenic properties. HPV are transmitted through direct skin-to-skin contact, and approximately 30 types are transmitted sexually. LR HPV are much more common than HR HPV among humans and often do not cause any symptoms. In fact, only 18 types of HPV pose a cancer risk, mostly for anogenital cancers.

Human papilloma virus particles lack a lipid envelope and are relatively small, with a diameter of only about 30 nm. In comparison, the human immunodeficiency virus (HIV) and influenza virus virions are enveloped by a lipid bilayer derived from the host cell and are approximately four times larger. The papillomavirus genome consists of double-stranded DNA decorated and packed by histones of the host cell. It encodes two types of proteins, early (E) proteins and late (L) proteins: early HPV proteins maintain regulatory functions (and are responsible for oncotransformation of the host cell in the case of HR types), and late proteins form the capsid of the virion. The life cycle of HPV is bound to the life cycle of its host cells, keratinocytes, and HPV can only be cultivated in special organotypic raft cultures containing a population of cells at different developmental stages — similar to the skin of a living organism [18,19 and 20]. Keratinocytes are the main cells of epidermis, the outermost layer of the skin. Actively dividing young keratinocytes are found near the basal membrane that separates the epidermis from other layers of the skin and move towards the skin surface during maturation. Viral particles infect non-differentiated cells, and new virions are produced inside the keratinocytes during the terminal stage of differentiation.

Late proteins of HPV form the viral capsid and mediate packaging of DNA into the virion. The pentamer-forming L1 protein is the major component of the HPV capsid [23], and the L2 protein is a minor constituent. The HPV capsid looks roughly spherical, but, in fact, it has a icosahedral symmetry with the triangulation number that equals 7. Rather than a structure based on pentamers mixed with hexamers (like that of the soccer ball), the HPV capsid is composed of 72 L1 pentamers of two different types — 60 hexavalent pentamers and 12 pentavalent pentamers (reviewed in 2, chapter 3). Remarkably, the fold of HPV L1 proteins is similar to that of human nucleoplasmins, the proteins that regulate the assembly of nucleosomes [24]. Whether they share a common ancestor or whether their similarity is the result of convergent evolution is not yet clear. Perhaps the interaction between L1 and nucleosomes on viral DNA is crucial for the encapsidation of the HPV genetic material.