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Journal of Virology, May 2001, p. 4952-4953, Vol. 75, No. 10
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.10.4952-4953.2001
LETTERS TO THE EDITOR
Epidermodysplasia Verruciformis Defines a Subset of
Cutaneous Human Papillomaviruses
 |
LETTER |
In a very interesting and provocative article, Antonsson et al.
reported a high prevalence of known or as-yet-uncharacterized human
papillomavirus (HPV) genotypes on the healthy skin of immunosuppressed and immunocompetent individuals, as detected by a PCR approach (1). This demonstrates unambiguously the ubiquity and
great multiplicity of cutaneous HPVs, in agreement with previous
reports (2-5).
Most HPV genotypes or type candidates detected by Antonsson et
al. belong to a group of phylogenetically related viruses that were
originally found in skin lesions of patients suffering from epidermodysplasia verruciformis (EV), a rare genodermatosis
(7). The authors claim that it seems warranted to stop
designating these viruses as EV-associated HPVs because of their high
prevalence in healthy individuals (1, 2) and the high rate
of PCR detection in skin cancers of renal transplant recipients
(3). We cannot agree with this proposal because EV HPVs
display very specific biologic properties that are under the control of
specific cellular genes (7). Due to a recessive mutation
in a gene (EV1) mapped to chromosomal region 17q25 (8), EV
patients show an abnormal susceptibility to this specific group of HPVs
only, including the oncogenic HPV type 5 (HPV5) (7).
Infection results in pathognomonic pityriasis versicolor-like lesions,
red plaques, and flat wart-like lesions. A specific cytopathic effect
is linked to the high level of viral replication in differentiating
keratinocytes. Invasive squamous cell carcinomas of the skin which
develop in about half of the patients contain high copy numbers of HPV5
genomes and abundant transcripts of the E6 and E7 open reading frames
(7). Phenocopies of EV are exceptionally observed in
immunosuppressed patients (7).
The ubiquity of EV HPVs
a feature shared by all HPV genotypesand
their impressive genomic diversity led to the authors' conclusions regarding their commensalic nature (1). Our recent data
strongly suggest, however, that commensalism is not the only
alternative to EV (4-6). Whereas the prevalence of
antibodies to HPV5 L1 capsid protein is low (2 to 5%) in the general
population and in renal transplant recipients (4), HPV5
antibodies are elicited upon epidermal repair processes in patients
with burns or cutaneous autoimmune bullous diseases (5).
Extensive keratinocyte proliferation thus favors the expression of EV
HPVs which, in turn, could enhance epidermal regeneration and be
beneficial to their host. Conversely, the prevalence of HPV5 antibodies
(25%) and the high PCR detection rate (85%) of HPV5 DNA, among other
EV HPVs, in patients with psoriasis (4) suggest that
persistent expression of EV HPV genomes might participate in the
autoimmune processes of this disease (6). Psoriasis is a
chronic hyperproliferative, inflammatory cutaneous disorder with a
complex genetic background. The EV1 locus colocalizes with a major
susceptibility locus for familial psoriasis (8). It is
tempting to speculate that distinct defects affecting the same (still
unknown) gene may be involved in the two skin conditions, leading to a
somewhat less efficient host restriction in psoriasis (8).
We thus strongly believe that the term EV HPVs is relevant. The
identification of the EV1 gene is within reach (8), and this should open new avenues for understanding the role of EV HPVs in
the biology and pathology of the skin.
| |
FOOTNOTES |
*
Phone: 33 145688742
Fax: 33 145688966
E-mail: gorth{at}pasteur.fr
| |
REFERENCES |
| 1.
|
Antonsson, A.,
O. Forslund,
H. Ekberg,
G. Sterner, and B. G. Hansson.
2000.
The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses.
J. Virol.
74:11636-11641[Abstract/Free Full Text].
|
| 2.
|
Boxman, I. L. A.,
R. J. M. Berkhout,
L. H. C. Mulder,
M. C. Wolkers,
J. N. Bouwes Bavinck,
B. J. Vermeer, and J. ter Schegget.
1997.
Detection of human papillomavirus DNA in plucked hairs from renal transplant recipients and healthy volunteers.
J. Investig. Dermatol.
108:712-715[CrossRef][Medline].
|
| 3.
|
De Villiers, E. M.,
D. Lavergne,
K. McLaren, and E. C. Benton.
1997.
Prevailing papillomavirus types in non-melanoma carcinomas of the skin in renal allograft recipients.
Int. J. Cancer
73:356-361[CrossRef][Medline].
|
| 4.
|
Favre, M.,
G. Orth,
S. Majewski,
S. Baloul,
A. Pura, and S. Jablonska.
1998.
Psoriasis: a possible reservoir for human papillomavirus type 5, the virus associated with skin carcinomas of epidermodysplasia verruciformis.
J. Investig. Dermatol.
110:311-317[CrossRef][Medline].
|
| 5.
|
Favre, M.,
S. Majewski,
B. Noszczyk,
F. Maienfisch,
A. Pura,
G. Orth, and S. Jablonska.
2000.
Antibodies to human papillomavirus type 5 are generated in epidermal repair processes.
J. Investig. Dermatol.
114:403-407[CrossRef][Medline].
|
| 6.
|
Majewski, S.,
S. Jablonska,
M. Favre,
N. Ramoz, and G. Orth.
1999.
Papillomavirus and autoimmunity in psoriasis.
Immunol. Today
20:475-476.
|
| 7.
|
Orth, G.
1987.
Epidermodysplasia verruciformis, p. 199-243.
In
N. P. Salzman, and P. M. Howley (ed.), The papillomaviruses. The Papovaviridae, vol. 2. Plenum Press, New York, N.Y.
|
| 8.
|
Ramoz, N.,
L. A. Rueda,
B. Bouadjar,
M. Favre, and G. Orth.
1999.
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.
J. Investig. Dermatol.
112:259-263[CrossRef][Medline].
|
| | | | |
Gérard Orth*
Michel Favre
Unité des Papillomavirus
Institut Pasteur
25 rue du Dr Roux
75015 Paris, France
|
| | | | |
Slavomir Majewski
Stefania Jablonska
Department of Dermatology
Warsaw School of Medicine
Warsaw, Poland
|
| |
AUTHORS' REPLY |
We thank Orth et al. for their interest in our study of skin
papillomaviruses (HPVs). We agree that patients suffering from epidermodysplasia verruciformis (EV) show a specific susceptibility to
certain HPV types, causing different clinical manifestations. However,
HPV was originally found among these patients by relatively insensitive
methods (10, 11), whereas recently, with highly sensitive
PCR methods, the EV HPVs have also been identified with high prevalence
in healthy skin of both the healthy population and immunosuppressed
patients (1, 4) as well as in skin cancer lesions of renal
transplant recipients (2, 3, 5, 6, 9).
A ground for our suggestion of only using the phylogenetic supergroup
classification (12) for the skin HPV types is the fact
that the EV HPVs are not restricted to EV patients. Furthermore, there
is a continuous emergence of new HPV type candidates, phylogenetically linked to the previously known EV HPVs by their DNA sequence, although
not discovered in EV patients.
Since we found an array of HPVs on healthy skin, we believe in a
commensalic nature of these viruses in healthy individuals. However, as
pointed out by Orth et al., there are certain conditions with extensive
keratinocyte proliferation where these HPVs might display specific
biological properties, such as in patients with psoriasis
(8) or burns or in patients with bullous diseases (7).
| |
FOOTNOTES |
*
Phone: 46 40331365 Fax: 46 40337312 E-mail:
annika.antonsson{at}mikrobiol.mas.lu.se
| |
REFERENCES |
| 1.
|
Antonsson, A.,
O. Forslund,
H. Ekberg,
G. Sterner, and B. G. Hansson.
2000.
The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses.
J. Virol.
74:11636-11641.
|
| 2.
|
Bens, G.,
U. Wieland,
A. Hofmann,
R. Hopfl, and H. Pfister.
1998.
Detection of new human papillomavirus sequences in skin lesions of a renal transplant recipient and characterization of one complete genome related to epidermodysplasia verruciformis-associated types.
J. Gen. Virol.
79:779-787[Abstract].
|
| 3.
|
Berkhout, R. J.,
L. M. Tieben,
H. L. Smits,
J. N. Bavinck,
B. J. Vermeer, and J. ter Schegget.
1995.
Nested PCR approach for detection and typing of epidermodysplasia verruciformis-associated human papillomavirus types in cutaneous cancers from renal transplant recipients.
J. Clin. Microbiol.
33:690-695[Abstract].
|
| 4.
|
Boxman, I. L.,
R. J. Berkhout,
L. H. Mulder,
M. C. Wolkers,
J. N. B. Bavinck,
B. J. Vermeer, and J. ter Schegget.
1997.
Detection of human papillomavirus DNA in plucked hairs from renal transplant recipients and healthy volunteers.
J. Investig. Dermatol.
108:712-715.
|
| 5.
|
de Jong-Tieben, L. M.,
R. J. Berkhout,
H. L. Smits,
J. N. B. Bavinck,
B. J. Vermeer,
F. J. van der Woude, and J. ter Schegget.
1995.
High frequency of detection of epidermodysplasia verruciformis-associated human papillomavirus DNA in biopsies from malignant and premalignant skin lesions from renal transplant recipients.
J. Investig. Dermatol.
105:367-371[CrossRef][Medline].
|
| 6.
|
de Villiers, E. M.,
D. Lavergne,
K. McLaren, and E. C. Benton.
1997.
Prevailing papillomavirus types in non-melanoma carcinomas of the skin in renal allograft recipients.
Int. J. Cancer
73:356-361.
|
| 7.
|
Favre, M.,
S. Majewski,
B. Noszczyk,
F. Maienfisch,
A. Pura,
G. Orth, and S. Jablonska.
2000.
Antibodies to human papillomavirus type 5 are generated in epidermal repair processes.
J. Investig. Dermatol.
114:403-407.
|
| 8.
|
Favre, M.,
G. Orth,
S. Majewski,
S. Baloul,
A. Pura, and S. Jablonska.
1998.
Psoriasis: a possible reservoir for human papillomavirus type 5, the virus associated with skin carcinomas of epidermodysplasia verruciformis.
J. Investig. Dermatol.
110:311-317.
|
| 9.
|
Hopfl, R.,
G. Bens,
U. Wieland,
A. Petter,
B. Zelger,
P. Fritsch, and H. Pfister.
1997.
Human papillomavirus DNA in non-melanoma skin cancers of a renal transplant recipient: detection of a new sequence related to epidermodysplasia verruciformis associated types.
J. Investig. Dermatol.
108:53-56[CrossRef][Medline].
|
| 10.
|
Kremsdorf, D.,
S. Jablonska,
M. Favre, and G. Orth.
1983.
Human papillomaviruses associated with epidermodysplasia verruciformis. II. Molecular cloning and biochemical characterization of human papillomavirus 3a, 8, 10, and 12 genomes.
J. Virol.
48:340-351[Abstract/Free Full Text].
|
| 11.
|
Orth, G.,
S. Jablonska,
M. Favre,
O. Croissant,
M. J. Chorzelska, and G. Rzesa.
1978.
Characterization of two types of human papillomaviruses in lesions of epidermodysplasia verruciformis.
Proc. Natl. Acad. Sci. USA
75:1537-1541[Abstract/Free Full Text].
|
| 12.
|
zur Hausen, H.
1999.
Papillomaviruses in human cancers.
Proc. Assoc. Am. Physicians
111:581-587[CrossRef][Medline].
|
| | | | |
Annika Antonsson*
Ola Forslund
Bengt
Göran Hansson
Department of Medical Microbiology
Malmö University Hospital
Lund University
Malmö, Sweden
|
| | | | |
Henrik Ekberg
Gunar Sterner
Department of Nephrology and Transplantation
Malmö University Hospital
Lund University
Malmö, Sweden
|
Journal of Virology, May 2001, p. 4952-4953, Vol. 75, No. 10
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.10.4952-4953.2001
