Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage
Patent
1993-02-11
1997-04-29
Nucker, Christine M.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving virus or bacteriophage
4352351, 4241881, 4242081, G01N 3353, C12N 700, C12N 701, A61K 3921
Patent
active
056247958
DESCRIPTION:
BRIEF SUMMARY
This application was filed under 35 U.S.C. .sctn. 371 based upon PCT application EP91/01108, filed Jun. 14, 1991.
Substantial progress has been made in our understanding of the acquired immunodeficiency syndrome or AIDS. The principal causative agent has been demonstrated to be a non-transforming retrovirus with a tropism for T4 helper/inducer lymphocytes (1, 2) and it has been estimated that millions of people world-wide have already been infected. Infection with this virus leads, at least in a significant percentage of cases, to a progressive depletion of the T4 lymphocyte population with a concomitant increasing susceptibility to the opportunistic infections which are characteristic of the disease.
Epidemiological studies indicate that human immunodeficiency virus, type 1 (H1V-1), the etiological agent responsible for the majority of AIDS cases, is currently the most widely disseminated HIV and is predominant in Central Africa, Europe and the U.S.A.
A second group of human immunodeficiency-associated retroviruses, human immunodeficiency virus type 2 (HIV-2), was identified in West Africa (3, 4). An HIV-2 virus is disclosed in EPO-0 239 425. An HIV-1 virus is disclosed in WO 86/02383.
One characteristic of human immunodeficiency, viruses which complicates their comparison is their genetic variability,; genetic variants arise spontaneously and with high frequency. A comparison of various HIV-1 isolates revealed that some regions of the genome are highly variable while others are reasonably well conserved (5-10). Similar polymorphisms have also been observed for HIV-2 (11). The regions with the greatest genetic stability are presumably those regions coding for the regions of vital proteins which are structurally or enzymatically essential. The vital genes with the greatest overall genetic stability are the gag and pol genes, while some regions of the env gene and the genes coding for regulatory proteins such as rev. tat. sor and nef exhibit a high degree of variability. Some of the major structural features of the gag and pol gene products are apparently shared not only by all of the variants of a particular HIV-type, but have, at least to some extent, been conserved between virus types.
Antiserum produced against HIV-1 cross-reacts with the gag and pol gene products of HIV-2, albeit with a lower affinity than for the corresponding HIV-1 gene products, but no serological cross-reactivity is observed for the envelope proteins. However, in spite of the demonstrable immunological cross-reaction, there is only modest sequence homology at the nucleic acid level indicating that HIV-1 and HIV-2 are genetically distinct, and no significant hybridization between these two viruses can be detected except under very low stringency conditions (11).
The simian immunodeficiency viruses, or SIVs, are non-human primate lentiviruses that are the closest known relatives of the HIVs. SIVs have been previously isolated from macaques (Siv.sub.mac) (12, 13), sooty mangabeys (SIV.sub.sm) (14, 15), African Green Monkeys (SIV.sub.AGM)(16) and mandrills (SIV.sub.MND)(17).
Mangabeys, green monkeys and mandrills are African old world primates, whereas macaques are Asian old world primates. These four SIVs fall into three discrete groups based on genetic sequence analysis, with SIV.sub.mac and SIV.sub.sm forming a single genetic group (18). Macaques are apparently not infected with SIV in their native habitat (19). It seems likely, therefore, that some individual macaques became infected with SIV.sub.sm from sooty mangabeys at US Regional Primate Centers (20).
HIV-2 is no more different from SIV.sub.sm at the sequence level than individual SIV.sub.sm isolates are different from each other (18, 21).
SIV.sub.AGM and SIV.sub.MND are distinct from HIV-1 and HIV-2, SIV.sub.MND seems to be more or less equidistant from HIV-1 and HIV-2 (22) while SIV.sub.AGM is closer to HIV-2 than to HIV-1 (23). Serological cross-reactivity has been observed between structural proteins of different HIV/SIVs. At the level of the envelope proteins, cross-react
REFERENCES:
Huet et al: "Genetic organization of a chimpanzee lentivirus related to HIV-1" Nature vl. 345 356-359 24 May 1990.
Peeters et al: "Isolation and partial characterization of an HIV-related virus occurring naturally in chimpanzees in Gabon" AIDS vol. 3 No. 10 pp. 625-630 (1989).
Peeters et al., 1990, v Intl. Conf. AIDS p. 598, Abstract W.C.P. 40.
Huet et al., 1990, Nature 345:356-359.
Peeters et al., 1989, AIDS 3:625-630.
Delaporte Eric
Peeters Martine
Piot Peter
Van Der Groen Guido
Innogenetics N.V.
Nucker Christine M.
Parkin Jeffrey S.
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