A (t) The Spongifrom
Encephalopathy (SE) is a lesion, described for the human
beings in the Creutzfeldt Jacob disease (CJD), the
Gerstmann-Straüssler-Scheinker syndrome, the fatal
familial insomnia, the Kuru, and for the animals,
particularly in the frame of the epidemy of Bovine
Spongiform Encephalopathy (BSE), responsible for the actual
crisis of mad cow. The pathologic form of prion (mutated
form) would be the causal agent of these SE (SB. Prusiner,
1981). Other authors (L. Manuelidis, 1995) have suggested
that a retrovirus (not yet identified) could intervene as a
causal agent.
SE lesions have been
described on histological sections from the brain of a
patient suffering from AIDS dementia (J. Schwenk, 1987).
These lesions have been since described (J. Artigas, 1989)
for 5 other HIV+ patients. However, a publication recently
reported 67 cases of SE on 200 autopsies of patients dead of
AIDS (AJ Martinez et coll., Path. Res. Pract. 191, 427-443,
1995). This lesion appears not to be an epiphenomenon, but
maybe a major component of AIDS. It is moreover surprising
that Pr DORMONT, a mad cow crisis expert of the health
Ministry did not quote these references in the synthesis
article he recently published, more precisely in the part
where the human diseases, particularly the spongiform
encephalopathy is described (Virologie, 1, 11-22,
1993).
According to J. Scwenk and
J. Artigas, the apparition of this spongiosis could have
been induced by the HIV or the etiologic agent of the CJD.
In this last hypothesis, HIV would accelerate this
apparition, as the CJD symptomatic expression generally
appears after more than twenty years of incubation (in a
similar manner to the JC virus, the agent of another
encephalitis of AIDS, the progressive multifocal
leukoencephalitis, that is clinically expressed when
simultaneously infected by the HIV).
As the CJD remains a rare
disease, it seems probable that the ES observed during AIDS
is secondary to the HIV or cofactors action, that could also
intervene during spongiosis occuring in other diseases. A
study showed that the mRNA of the prion presents in its loop
a pentanucleotide similar to the TAR region of the HIV. The
HIV TAT protein (that interacts with TAR) induces
in
vitro the
expression of a prion gene in human astrocytes (EG.
Müller Werner et coll., VII Int. Conf. On AIDS,
Florence, 1991), wich could increase the number of
transconformations of prion into pathologic forms. Another
argument is given by the molecular homologies between the
HIV GP 110, snake venom and the prion, only in its mutated
shape (MKG. Tran, V European Conf. On Clinical Aspects and
Treatments of HIV Infection, Copenhague, 1995).
We can also ask wether it
is necessary for cofactors to intervene to make the ES
appear during the HIV infection, or other déesses
like CJD. In this second hypothesis, retroviruses (HIV or
the supposed agent of CJD) would intervene by themselves as
ES cofactors, that would then intervene with other cofactors
(like anorexia, proposed by J. Artigas), hence favouring the
prion mutation. Among these hypothetic cofactors, two appear
important to us, as they directly concern the bovine
livestock and the human beings. They are Dioxin and
Distilben (Diethylstilbestrol).
Dioxin is an extremely
toxic molecule, even at very low doses. Furthermore, it is
very difficult to detect and to dose. It has been known
since 1976 (Seveso, France) that numerous dioxin leaks have
occured in the atmosphere. Non negligible quantities have
been detected in human fat tissus, in marine organisms, in
mother milk and cow milk. It must be know that dioxin
increases in vitro from 3 to 6 times the HIV reverse
transcriptase activity, and from 4 to 8 times the production
of viral particules. What more, the main toxicity of dioxin
is immunological and concerns, like the HIV, on T4
lymphocytes. The use of orange agent (contain dioxin) between 1961 and
1971 during the Vietnam war has provoked cancers and
congenital malformations. High amounts of dioxin have then
been noted among Vietnamians who had never been exposed to
the orange
agent. Americans
have made tests that revealed the mutagenic and cancerogenic
effects of dioxin. A law called "orange agent act" has even been voted by the
congress in 1991, establishing an "official presumption of
relation with the service" in the case of Vietnam war
veterans suffering from lymphomas or sarcoma. It has
also been noted an increase of cancers among paysants in
Kansas and Nebraska that had been exposed to dioxin.
Distilbene (DES) has been
used for decades for bovines "hormon calf". In 1979, the
Food and Drug Administration in the United States officially
prohibed the use of DES for the cattle, because of its
cancerigenic power, finally admitted for human beings by
direct action (the best known being the vagina cancer,
occuring for young women more than twenty years after their
mother took DES during their pregnancy), or by ingestion.
Ten years later, a similar decision was taken by most of the
european countries, but neither England nor Ireland. A test,
made at a time when HIV had not been yet identified, showed
that after induction of renal tumors on hamsters, C ARN
viruses (retroviruses) appeared during the experimentation,
without a possible explanation (A.H. Dodge, Labor. Invest.,
31, 3, 250-257, 1974). Bojan et coll. (1976), also showed
that the administration of DES, simultaneously, preceeding
or following urethane in mice induced the apparition of
lymphomas. The intraperitoneal injection of thymus and
spleen of these mice to newborn mice reproduced the same
type of tumors : a lymphoblastic lymphosarcoma (similar to
the H type of lymphoblastic lymphosarcoma, the most
frequently observed in AIDS). The apparition of C type viral
particules out of the cells had been also noted. Untill now,
it has not been demonstrated that DES intervene during HIV
infection. But it must been known that DES induces cancers
similar to the most frequent cancers noted during the HIV
infection, and also lymphomas, Kaposi's sarcoma. Other
pathological states described during the HIV infection are
reported with DES : T lymphocyte fall, toxoplasmosis,
cryptococcosis, auto-immune diseases, papillomavirus
infections.
As a part of the cattle,
as well as some humans, have been submitted for decades to
the effects of dioxin, and then anomalies could have been
transmitted from one generation to the next, it appears that
studies should be rapidly carried out in order to determine
wether dioxin and DES would be cofactors in BSE and/or
retroviral infections like AIDS. (9711)
