D'Incan, M.

Desgranges, C.

Gasmi, M.

Souteyrand, P.

Elsevier - Publisher Connector 

LETTERS TO THE EDITOR 
Deleted HTL V Retrovirus May Be Involved in the Development of 
Cutaneous T-Cell Lymphomas 
To the Editor: 
In an interesting recent article, Lisby et al [1] reported the absence of 
HTLV -I (human T lymphotropic virus type I) or HTLV -I - related 
provirus in DNA of skin lesions of 21 patients with a cutaneous 
T-cell lymphoma (CTCL) and seronegative for HTLV-I. They 
used the very sensitive polymerase chain reaction technique (PCR) , 
with 10 primer pairs that amplify the conserved sequences between 
HTL V -I and HTL V -II, and span the pol (between nucleotides 2693 
and 3345), env (between nucleotides 6157 and 6496), and taxlLTR 
(between nucleotides 7480 and 8659) genes. Their conclusions 
were as follows: 1) as sensitive as the PCR procedure is, there is no 
HTLV-I-related genome in the skin specimens of CTCL; 2) the 
putative virus associated with CTCL is distantly related to HTLV-I 
and thus, the HTLV-I -specific primers did not amplify it, even in 
low-stringency conditions of annealing; and 3) the infection by 
HTL V -I was processed on the "hit and run" mode, in which the 
virus disappeared during the evolution of the disease. 
We agree totally with these conclusions but we wish to suggest a 
fourth possibility, which is the infection by a largely deleted 
HTLV-I provirus. Indeed, deleted retroviruses are known to be 
associated with some leukemic processes in animals (e.g., FTL V in 
feline leukemias [2]) and in humans (HTL V -I in some cases of adult 
T-cell lymphoma [3]). During the period when the article of Lisby 
et al was submitted, Hall et al [4] reported the case of an American 
patient with mycosis fungo ides who was seronegative for HTL V-I, 
and from whom a B-cell line was established and found to be in-
fected by a largely deleted HTLV-I provirus. This deletion spanned 
the entire pol gene and parts of the gag and env genes . Moreover, 
using PCR, these authors found the HTLV -I provirus with variable 
deletions in cutaneous lesions of five additional patients with 
CTCL. In addition, using PCR, we have looked recently for the 
association between HTLV -I and CTCL in a series of 51 patients 
with CTCL who were seronegative for HTLV-I [5] in a nonende-
mic area for HTLV-I in France. We detected a HTLV-I provirus 
deleted in the pol region in the peripheral lymphocytes of a woman 
with mycosis fungoides. In accord with Hall et ai, we think that it 
cannot be excluded that deleted retrovirus may playa role in the 
pathogenesis of CTCL, and that, as these deletions seem to be vari-
able from patient to patient, this could be an explanation for the 
negative results of the PCR search. Moreover, a large deletion in the 
pol gene would explain a low (or absent) production of viral anti-
genic proteins and the seronegativity for HTLV-I of patients with 
CTCL [4]. Finally, in nonendemic areas the incidence of HTLV 
infection in CTCL is probably low, because the virus was detected 
in only one of 51 cases in our series. 
M. D'Incan, P. Souteyrand, M. Gasmi, and C. Desgranges 
Department of Dermatology 
Hotel-Dieu, CHRU Clermont-Ferrand 
INSERM U271, Lyon, France 
REFERENCES 
1. Lisby G, Reitz MS Jr, Lange-Vejlsgaard G: No detection of HTLV-I DNA in 
punch skin biopsies from patients with cutaneous T-cell lymphoma by the 
polymeme chain reaction.] Invesl DermaloI98:417 - 420, 1992 
2. Weiss RB: Defective virus to blame? Nature 338:458, 1989 
3. Wong-Staal F, Hahn B, Manzari V, el ./: A survey of human leukemias for se-
quences of a human retrovirus. Na/llre 302:626 - 628, 1983 
4. Hall WW, Liu CR, Schneewind 0, el al: Deleted provirus in blood and cutaneous 
lesions of patients with mycosis fungoides. Science 253:317 - 320, 1991 
5. D'lncan M, Souteyrand P,Bignon YJ,etal: Retroviral sequences related to HTLV-I 
in circulating lymphocytes from a seronegative patient with a mycosis fungoides 
and study of 51 cutaneous T -cell lymphornas outside HTLV -I endemic areas.Eur 
] Dermato/2:363-371, 1992 
REPLY 
Weare pleased that D'lncan et al agree with our conclusions [1]. We 
wish, however, to emphasize that the second and third "conclu-
sion" cited by D'Incan et af were hypothetical discussions put for-
ward by us and not conclusions based upon our experiments [1 J. 
The possibility put forward by D'Incan et af, that a largely deleted 
HTLV-l provirus is involved in the pathogenesis of CTCL, is not 
supported by the experiments described in our article. Our 10 
primer sets detect conserved HTL V -I/ll proviral sequences from 
position 1703 to position 8659 (10 fragments within the 6957 
bases) in the prototype HTL V -I genome, and a deletion thus has to 
be even larger to be "overlooked" in our setup, or,less likely, consist 
of several deletions covering all our target regions. The 5.5-kilobase 
deleted HTLV -I provirus reported by Hall et af [2] would have been 
detected by our two tax/L TR primer sets, and is not present in our 
patient group. We do not agree with the suggestions by D'Incan et al 
that the negative results by polymerase chain reaction could be 
explained by variation from patient to patient in the deletions af-
fecting the putative integrated HTLV -I provirus. We find it very 
unlikely that all of our patients should have deletions covering aliI 0 
target sequences. Although we wish to emphasize that our findings 
do not support a role for HTLV -I/II or an HTLV -I/II - related virus 
in patients with CTCL, we agree with D'Incan et af that such a virus 
could be present in a small subset of CTCL patients. However, 
because D'Incan et af found a deleted HTLV-I provirus in one of 51 
patients with CTCL, and we did not find HTLV-I/II or an HTLV-
Illl - related provirus in any of 21 patients with CTCL, it is unlikely 
that such a virus could playa major role in the pathogenesis of 
CTCL, at least in the two patient populations described here. 
REFERENCES 
1. LisbyG, Reitz MSJr, Vejlsgaard GL: No detectiollofHTLV-1 DNA in punch skin 
biopsies from patients with cutaneous T -cell lymphoma by the polymerase chain \ 
reaction.] Invest DermatoI98:417 - 420, 1992 
2. Hall WW, Liu CR, Schneewind 0, el al: Deleted provirus in blood and cutaneous 
lesions of patients with mycosis fungoides. Scietlce 253:317 -320,1991 
Gunhild L. Vejlsgaard 
Department of Clinical Microbiology 
University of Copenhagen, Herlev Hospital 
DK-2730 Herlev, Denmark 
Gorm Lisby 
Professor, Department of Dermatology 
U l1iversity of Copenhagen, Rigshospitalet 
DK-2100 Copenhagen, Denmark 
0022-202X/94/S07.00 Copyright © 1994 by The Society for Investigative Dermatology, Inc. 
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