Volume 9 Supplement 1

Abstracts from the 17th International Symposium on HIV and Emerging Infectious Diseases (ISHEID)

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)

Retrovirology20129(Suppl 1):P24

https://doi.org/10.1186/1742-4690-9-S1-P24

Published: 25 May 2012

Background

The AIDS hallmark is the simultaneous fall in CD4 and rise in CD8 T lymphocytes. Interestingly, this very pathognomonic 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 heptapeptide (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 : GWCFEVEEDTEGETNSLLHPISQHGMEDPERQVLVWRFNSRLAFEHKARLMHPEFYKNC Notch : GWLLD…FEQDSEGETNSLPHLISQHAL ANPEMQALA-HGKSRLAFEHQVRLSHLPVANNC It included the Nef LL and ED doublets precisely implicated in CD4 down-regulation and EE in β-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).

Authors’ Affiliations

(1)
Clermont-Ferrand University, Hospital Hotel-Dieu, Public Health
(2)
Association POSITIFS

Copyright

© Tran et al; licensee BioMed Central Ltd. 2012

This article is published under license to 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.

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