Group O HIV-1, fragments of such viruses, and uses thereof

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage

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5303894, 530324, 530350, 53038835, 435 6, 435 71, 435 691, 4241601, 4241881, 4242081, 536 2372, C12Q 170, C12Q 168, C07K 1600, A61K 3942

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active

060307692

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

1. Field of the Invention
The present invention relates to retrovirus strains of the HIV-1 group, group O, and in particular the strains called BCF02 (ESS), BCF01 (FAN), BCF06 (LOB), BCF07 (MAN), BCF08B (NKO), BCF11 (NAN) and BCF03 (POC), to fragments of the said retroviruses and to their applications as diagnostic reagent and as immunogenic agent.
2. Description of the Background
Two distinct types of HIV (human immunodeficiency virus: HIV-1 and HIV-2) have been described and are the agents responsible for AIDS. Analysis of their nucleic acid sequence has made it possible to identify various subtypes of HIV-1, although no correlation could be established between variability and pathogenicity. Similarly, HIV-2 exhibits a greater genetic and biological diversity than that previously envisaged.
Analysis of nucleotide fragments of various HIV-1 isolates has shown the existence, through the analysis of the env gene, of at least 7 different subtypes, called A to G (MYERS G. et al., Human retroviruses and AIDS, 1993, Los Alamos Nat. Lab.).
More recently, two other isolates, considered to be considerably more distant from the other 7 subtypes, that is to say whose sequence homology is the most distant from that of the reference HIV-1 strains, have also been isolated: HIV-1ANT70 and HIV-1MVP5180, obtained from Cameroonian patients, and have been attached to a new HIV-1 group, group O, as opposed to group M corresponding to the 7 abovementioned A-G subtypes, taking into account their genomic organization (5' LTR Gag Pol Vif Vpu Vpr Tat Rev Env Nef LTR 3'), (Patent Application WO 89/12094, European Patent Application No. 0,591,914, GuURTLER L. G. et al., J. Virol., 1994, 68, 1581-85).
Analysis of the DNA sequences has shown 65-70% similarity with HIV-1 and 56% with HIV-2.
By using a competition immunoblotting method, using a peptide V3 from MVP5180, a 7-8% prevalence is found in Yaounde. This prevalence might be underestimated since the V3 loop is known, in all the HIV-1 subtypes, to be a highly variable region. Molecular studies also indicate the presence of group O virus in Gabon, France, Spain and Germany.
Ongoing serological studies reveal group O HIV-1 infections in Nigeria, Niger and Senegal.
Knowledge of these various groups and subtypes is particularly important for developing: and specific, that is to say which do not lead to false-negative or false-positive results; and entire group O viruses.
Indeed, it has been shown, in particular, that some detection reagents were not sufficiently sensitive and did not always make it possible to detect group O HIV-1 infections (LOUSSERT-AJAKA I. et al., Lancet, 1994, 343, 1393-94), which has led to the withdrawal of three screening kits and to the declassification of two others on the French market.
The results show that the group O viruses are very distant from the group M HIV-1 subtypes. These results indicate that the HIV-1 viruses ought to be classified in two different groups, namely: HIV-1 M and HIV-1 O. The group O viruses appear to be capable of being transmitted by horizontal and vertical routes, leading to a very wide distribution of this infection. The pathogenicity of these viruses is under study. The divergence of these viruses should be taken into account in the sensitivity of diagnostic tests and in the development of vaccines.


SUMMARY OF THE INVENTION

Consequently, the Applicant set itself the objective of providing fragments, derived from selected group O HIV-1 strains, capable of allowing both detection of the entire group O HIV-1 viruses and specific intra-group O differentiation and which are also capable of inducing protection against the entire HIV-1 subtypes, including group O, which fragments make it possible to avoid obtaining false-negative or false-positive results; to do this, the inventors selected a set of strains and sequences, derived essentially from a region of the env gene, in particular at the level of a hypervariable fragment situated in the V3 loop (C2V3) or at the level of gp41 and of a region of th

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