C.51. Bangkok:

WePeA5599 Poster

Atherosclerosis and AIDS : Homology between atherogenic Marek's herpes virus and LDL receptor, between cytomegalovirus (CMV) and LDL-related receptor, and between HIV-1 VIF and phospholipase A2.

Auteurs : TRAN Guy Mong Ky (1, 5), CAPRANI Adrien (3, 5), KIRKIACHARIAN Serge (2), MAURISSON Gilbert (4, 5).

1 University Paris-Sud XI ; correspondence: 31 Av du Bois, Châtenay-Malabry, France. E-mail : mkg_tran@yahoo.fr
2 Therapeutic Chemistry, Faculty Pharmacy, University Paris-Sud XI, Châtenay-Malabry. E-mail : serge.kirkiacharian@cep.u-psud.fr.
3 University 7-Denis Diderot, CNRS Tour 33/34 ESA7057, 2 Place Jussieu, Paris Cedex 05. E-mail : caprani@ccr.jussieu.fr.
4 Centre Médical Europe, 44 rue d'Amsterdam, Paris. E-mail : maurisson@club-internet.fr.
5 Association Positifs, BP 230 75865 Paris Cedex 18. E-mail : positifs@positifs.org

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Aids is characterized by the occurrence of severe atherosclerosis in very young patients. This prompted us to look for the physiopathology of atherosclerosis in this especially susceptible but unusual population. Our objective is to screen for viruses inducing atherosclerosis.

We looked on Marek's herpes virus (Fabricant C.G., 1978), which can induce in chicken coronary disease even with a diet without cholesterol. CMV is also a good candidate, as it enhances the recurrences of coronary stenosis after stent. Lastly, in transgenic mouse, phospholipase A2 is responsible of atherosclerosis (Ivandic B., 1999). By comparison of amino acid sequences, we found 3 significant homologies :

1) Marek's herpes virus 132bp repeat (sequence LHTS... TICRNK FLCLLP) ...is a rabbit LDL cholesterol receptor ( repeat V)-like (CIHSSÉSLC-ss-CKNK... RQFVC-ss-CPVL) in tridimensional cysteine bridged [-ss-] structure.
2) CMV TRL6 (sequence WKTV...DQWLCNVTGIGNAT) is a LDL related receptor-like. (WHSV...QWLCD).
3) HIV-1 VIF protein has the tridimensionnal structure and active site residues (His, Ser) of a phospholipase A.

Conclusion: These striking homologies between virus and cholesterol receptors, and between HIV-1 VIF and phospholipase A may explain the abnormal occurrence of severe atherosclerosis in such a young population as AIDS. Treatment must focus on anti-herpes virus drugs (and bee propolis, an antiviral natural product) as well as on VIF for a component of AIDS vaccine and anti-phospholipase drug.

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CD B11240 Communication

Immune Reconstitution by DHEA-

A significant Clinical Case

CAPRANI A. ^{1, 2}, Richert A. ^{1, 2}, MAURISSON G.^{1, 3}

1 Association Positifs, BP 230 75865 Paris Cedex 18. E-mail : positifs@positifs.org
2 University 7-Denis Diderot, CNRS Tour 33/34 ESA7057, 2 Place Jussieu, Paris Cedex 05. E-mail : caprani@ccr.jussieu.fr.
3 Centre Médical Europe, 44 rue d'Amsterdam, Paris. E-mail : maurisson@club-internet.fr.

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Background: DHEA prevents TH1 and TH2 imbalance, known to contribute to the progression of HIV. Moreover, HIV+ patients show generally a decline of DHEA blood level.

Method: Blood DHEA sulphate(DHEAS), cortisol, CD4 and CD8 counts were measured for an HIV+ patient presenting initially a low DHEAS/cortisol level, during supplementation by 7-keto DHEA for 16 months

Results : A DHEA supplementation of a 60 year old osteoporotic patient HIV+ since 20 years, with a stable biological and clinical state during the preceeding two years (CD4 =325±20/mm3; viral load< 50 copies/ml; DHEAS ª 700ng/ml; no opportunistic affections), was instituted in order to increase mass bone after failure of orthodoxic therapies. Supplementation was done with 7-keto DHEA (no hormon-dependent cancer risks); 50mg per os daily the first 3 months and 75mg daily the next 12 months.
After 3 months, blood DHEAS level increases to 1433ng/ml. At 6 and 9 months, DHEAS level increases to 2700ng/ml and then decreases to 1200ng/ml at 16 months. CD4 increases progressively, 407 (+24%) at 3 months, 520( +58%) at 6 months and then remains stable 515+/-22. This increase is highly significant (p<0.05).
In addition, the only biological parameter controlling mass bone which was drastically disturbed(PTH), was normalized, despite a contrasting effect on mass bone a the level of the osteoporotic(L1-L4), which increases drastically of 9,5% at 6 months, but decreases of 18% after 16 months.

Conclusion: Supplementation of DHEA in an HIV+ patient to restore a normal level leads to a drastic increase of CD4, comparable to that obtained with IL2, without inducing bone remineralisation able to couterbalance a well known side effect of HAART. This significant clinical case justify to undertake a large clinical trial.