Caprani, Adrien

Gerbaud, Laurent

Tran, Guy MK

Retrovirology

English

PubMed

Guy MK Tran

Adrien Caprani

Laurent Gerbaud

Crossref

POSTER PRESENTATION Open AccessCD4.CD8 ratio decrease in AIDS, explained by amolecular mimicry between African HIV-1 Nefand Notch-1. Nef as a target for vaccine andNF-Kb inhibitors (salicylate, resveratrol,curcumin,epigallocatechine-3-gallate)Guy MK Tran1,2*, Adrien Caprani2, Laurent Gerbaud1From 17th International Symposium on HIV and Emerging Infectious Diseases (ISHEID)Marseille, France. 23-25 May 2012BackgroundThe AIDS hallmark is the simultaneous fall in CD4 andrise in CD8 T lymphocytes. Interestingly, this very pathog-nomonic but unexplained decrease of CD4/CD8 ratio isalso characteristic of a member of the EGF family, Notch-1 function (Fowlkes BJ, 2002). Calenda V (1994) foundthat Nef hampered drastically bone marrow progenitorscells functionality. African HIV-1 strain NDK (Spire B,1989), which induced a fulminant AIDS killing the patientin only 15 days, decreases dramatically CD4 counts. Nef isthe most abundant HIV-1 protein in infected cells (85% ofmRNA). Nef is a superantigen, its action is amplified10,000 times compared to a common antigen.ObjectiveWe found previously Notch-1 in the LTR (Long TerminalRepeat) of another retrovirus [Mouse Mammary TumorVirus (MMTV)] (Tran MKG, Eurocancer, Paris, 1999). AsNef is located also in HIV-1 LTR, we looked for Notch-1in Nef.MethodsAmino Acid (AA) alignment between Epidermal GrowthFactor (EGF) family members (including Notch-1) andNef (Los Alamos HIV sequences Database, 2002).ResultsNef COOH-terminus of HIV-1 clade D African strains(from Congo Democratic Republic, Chad, Tanzania,Uganda, South Africa, Kenya,…), but not from otherparts of the world (other non-D clades), was a perfectmolecular mimetic of Notch-1: They shared a hepta-peptide (7 AA) SRLAFEH. The homology between Nef(Poon AFY, 2009) and Notch (BLASTP on mouseNotch-1) chimera was 67 AA long with 4 His, 1 Cysand 1 Trp (highly significant): Nef : GWCFEVEEDTE-GETNSLLHPISQHGMEDPERQVLVWRFNSRLAFEH-KARLMHPEFYKNC Notch : GWLLD…FEQDSEGETNSLPHLISQHAL ANPEMQALA-HGKSRLAFEHQVRLSHLPVANNC It included the Nef LL and EDdoublets precisely implicated in CD4 down-regulationand EE in b-COP recruitement(Benichou S.1994).ConclusionsThis opens new avenues for a vaccine targeted to Nef-Notch specific to Africa, a continent devastated by AIDSand tuberculosis (in South Africa, about 60% HIV-1infected patients had also tuberculosis).Author details1Clermont-Ferrand University, Hospital Hotel-Dieu, Public Health, Clermont-Ferrand, France. 2Association POSITIFS, Paris cedex 18, France.Published: 25 May 2012* Correspondence: positifpresident@yahoo.fr1Clermont-Ferrand University, Hospital Hotel-Dieu, Public Health, Clermont-Ferrand, FranceFull list of author information is available at the end of the articleTran et al. Retrovirology 2012, 9(Suppl 1):P24http://www.retrovirology.com/content/9/S1/P24© 2012 Tran et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.doi:10.1186/1742-4690-9-S1-P24Cite this article as: Tran et al.: CD4.CD8 ratio decrease in AIDS,explained by a molecular mimicry between African HIV-1 Nef andNotch-1. Nef as a target for vaccine and NF-Kb inhibitors (salicylate,resveratrol,curcumin, epigallocatechine-3-gallate). Retrovirology 2012 9(Suppl 1):P24.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitTran et al. Retrovirology 2012, 9(Suppl 1):P24http://www.retrovirology.com/content/9/S1/P24Page 2 of 2

CD4.CD8 ratio decrease in AIDS, explained by a molecular mimicry between African HIV-1 Nef and Notch-1. Nef as a target for vaccine and NF-Kb inhibitors (salicylate, resveratrol,curcumin, epigallocatechine-3-gallate)

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POSTER PRESENTATION Open Access
CD4.CD8 ratio decrease in AIDS, explained by a
molecular mimicry between African HIV-1 Nef
and Notch-1. Nef as a target for vaccine and
NF-Kb inhibitors (salicylate, resveratrol,curcumin,
epigallocatechine-3-gallate)
Guy MK Tran1,2*, Adrien Caprani2, Laurent Gerbaud1
From 17th International Symposium on HIV and Emerging Infectious Diseases (ISHEID)
Marseille, France. 23-25 May 2012
Background
The AIDS hallmark is the simultaneous fall in CD4 and
rise in CD8 T lymphocytes. Interestingly, this very pathog-
nomonic but unexplained decrease of CD4/CD8 ratio is
also characteristic of a member of the EGF family, Notch-
1 function (Fowlkes BJ, 2002). Calenda V (1994) found
that Nef hampered drastically bone marrow progenitors
cells functionality. African HIV-1 strain NDK (Spire B,
1989), which induced a fulminant AIDS killing the patient
in only 15 days, decreases dramatically CD4 counts. Nef is
the most abundant HIV-1 protein in infected cells (85% of
mRNA). Nef is a superantigen, its action is amplified
10,000 times compared to a common antigen.
Objective
We found previously Notch-1 in the LTR (Long Terminal
Repeat) of another retrovirus [Mouse Mammary Tumor
Virus (MMTV)] (Tran MKG, Eurocancer, Paris, 1999). As
Nef is located also in HIV-1 LTR, we looked for Notch-1
in Nef.
Methods
Amino Acid (AA) alignment between Epidermal Growth
Factor (EGF) family members (including Notch-1) and
Nef (Los Alamos HIV sequences Database, 2002).
Results
Nef COOH-terminus of HIV-1 clade D African strains
(from Congo Democratic Republic, Chad, Tanzania,
Uganda, South Africa, Kenya,…), but not from other
parts of the world (other non-D clades), was a perfect
molecular mimetic of Notch-1: They shared a hepta-
peptide (7 AA) SRLAFEH. The homology between Nef
(Poon AFY, 2009) and Notch (BLASTP on mouse
Notch-1) chimera was 67 AA long with 4 His, 1 Cys
and 1 Trp (highly significant): Nef : GWCFEVEEDTE-
GETNSLLHPISQHGMEDPERQVLVWRFNSRLAFEH-
KARLMHPEFYKNC Notch : GWLLD…FEQDSEG
ETNSLPHLISQHAL ANPEMQALA-HGKSRLAFEH
QVRLSHLPVANNC It included the Nef LL and ED
doublets precisely implicated in CD4 down-regulation
and EE in b-COP recruitement(Benichou S.1994).
Conclusions
This opens new avenues for a vaccine targeted to Nef-
Notch specific to Africa, a continent devastated by AIDS
and tuberculosis (in South Africa, about 60% HIV-1
infected patients had also tuberculosis).
Author details
1Clermont-Ferrand University, Hospital Hotel-Dieu, Public Health, Clermont-
Ferrand, France. 2Association POSITIFS, Paris cedex 18, France.
Published: 25 May 2012
* Correspondence: positifpresident@yahoo.fr
1Clermont-Ferrand University, Hospital Hotel-Dieu, Public Health, Clermont-
Ferrand, France
Full list of author information is available at the end of the article
Tran et al. Retrovirology 2012, 9(Suppl 1):P24
http://www.retrovirology.com/content/9/S1/P24
© 2012 Tran et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
doi:10.1186/1742-4690-9-S1-P24
Cite this article as: Tran et al.: CD4.CD8 ratio decrease in AIDS,
explained by a molecular mimicry between African HIV-1 Nef and
Notch-1. Nef as a target for vaccine and NF-Kb inhibitors (salicylate,
resveratrol,curcumin, epigallocatechine-3-gallate). Retrovirology 2012 9
(Suppl 1):P24.
Submit your next manuscript to BioMed Central
and take full advantage of: 
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at 
www.biomedcentral.com/submit
Tran et al. Retrovirology 2012, 9(Suppl 1):P24
http://www.retrovirology.com/content/9/S1/P24
Page 2 of 2


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CD4.CD8 ratio decrease in AIDS, explained by a molecular mimicry between African HIV-1 Nef and Notch-1. Nef as a target for vaccine and NF-Kb inhibitors (salicylate, resveratrol,curcumin, epigallocatechine-3-gallate)

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