Human papillomaviruses (HPV) cause various skin diseases and cancer of the uterine cervix, the second most common cause of death by cancer in women world-wide. The Papillomavirus Unit at Institut Pasteur, directed by Gérard ORTH, has just mapped the first chromosomal locus for predisposition to papillomavirus infection in individuals suffering from epidermodysplasia verruciformis (EV). This disease is an ideal model system for studies of susceptibility to HPV. The locus identified is particularly interesting because it may also be involved in predisposition to psoriasis, a skin disease affecting 2% of the population.
More than 100 types of human papillomavirus (HPV) have been discovered. They cause a variety of diseases, most of which are benign and affect the skin or mucous membranes (e.g. warts, anal and genital condylomas, laryngeal papillomas). However, some of these viruses are potentially carcinogenic. This is the case for HPV types 16 and 18, which are involved in cervical cancer, and HPV type 5, which is associated with skin cancers in individuals suffering from a rare skin disease, epidermodysplasia verruciformis (EV). This disease has been studied in detail over the last twenty years by Gérard Orth and his team. It is an ideal model system for studying human susceptibility to papillomaviruses, particularly those viruses that are oncogenic.
The Papillomavirus Unit had shown that individuals suffering from EV are highly prone to infection by certain HPV that are harmless to most of us, and that only EV patients develop cancers due to infection with HPV type 5. This virus only very rarely causes infection in the general population. Why are EV patients particularly susceptible to these HPV, and to cancers caused by HPV type 5?
Researchers at Institut Pasteur have now taken the first steps towards answering this question. They have carried out a genetic study of 3 consanguineous families affected by EV, in collaboration with Algerian and Colombian dermatologists, and have identified a locus likely to contain a gene conferring predisposition to this illness. Even more intriguing, the locus of this gene, EV1, has been mapped to a region of chromosome 17 known to contain a major locus for predisposition to familial forms of psoriasis (1).
In 1998, the researchers of the Papillomavirus Unit, in collaboration with Professor Jablonska and Polish dermatologists, demonstrated a link between the HPV implicated in EV and psoriasis. They detected HPV type 5 DNA in the lesions of 90% of individuals suffering from psoriasis and suggested that psoriasis may act as a reservoir of this virus (2).
A stimulating hypothesis is that EV and psoriasis are linked to defects in the same, single gene. Different mutations within this gene may predispose the individuals carrying them to one or other of these illnesses. Research is now being directed towards determining whether HPV type 5 is involved in the pathogenesis of psoriasis.
(1) "A susceptibility locus for epidermodysplasia verruciformis, an abnormal predisposition to infection with the oncogenic human papillomavirus type 5, maps to chromosome 17qter in a region containing a psoriasis locus " , Journal of Investigative Dermatology, March 1999.
(2) " Psoriasis : a possible reservoir for human papillomavirus type 5, the virus associated with skin carcinomas of epidermodysplasia verruciformis " : Journal of Investigative Dermatology, April 1998
Michel FAVRE*, Gérard ORTH*, Slavomir MAJEWSKI#, Samia BALOUL*, Anna PURA#, et Stefania JABLONSKA#.
* Papillomavirus Unit / Inserm U190, Institut Pasteur,
Paris.
# Department of Dermatology, Warsaw School of Medicine, Warsaw, Pologne.
- Gérard ORTH , Michel FAVRE , Papillomavirus Unit,
Institut Pasteur, Paris, FRANCE.
Tel : 33 01 45 68 87 43. E-mails : gorth@pasteur.fr, mfavre@pasteur.fr