Chemistry: molecular biology and microbiology – Spore forming or isolating process
Patent
1994-02-02
1997-07-22
Housel, James C.
Chemistry: molecular biology and microbiology
Spore forming or isolating process
4352351, 435239, 43524021, 4241841, 424 932, C12N 700, C12N 500, A61K 3712, A01N 6300
Patent
active
056503180
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to a medium for in vitro culture of cells infected by a virus present in individuals suffering from multiple sclerosis, a process for the production of infected cells using said medium and the infected cell lines thus obtained.
DESCRIPTION OF THE PRIOR ART
Multiple sclerosis (MS) is a demyelinizing disease of the central nervous system (CNS) which has been suspected for several years of being associated with a virus, although the causal agent still has not been determined with certainty.
Several works have supported this hypothesis of a viral etiology of the disease, but none of the known viruses tested has proved to be the causal agent sought.
Consequently, the observation in patients suffering from multiple sclerosis of phenomena comparable to an autoimmunity reaction has led to an "essential" autoimmune etiological hypothesis (Lisak R. P., Zweiman B. New Engl. J. Med. 1977; 297, 850-853, and Lassmann H. and Wisniewski H. M. Arch. Neurol. 1979; 36, 490-497). However, this autoimmunity directed against certain components of the central nervous system has proven to be not very specific to MS and frequent in inflammations of the CNS, which may or may not be associated with an infection, as was demonstrated by Hirayama M. et al. (Neurology 1986; 36, 276-8) Kenneth G. Warren et al. (Annals of Neurology 1986; 20, 20-25), Suzumura A. et al. (Journal of Neuroimmunology 1986; 11, 137-47) and Tourtelotte W. et al. (Journal of Neurochemistry 1986; 46, 1086-93). Furthermore, as noted by E. J. Field (The Lancet 1989; 1, 1272), none of the immunosuppressive therapeutic agents has allowed decisive results against MS to be obtained.
One hypothesis has been put forward, according to which a retrovirus is said to be the cause of the disease. The discovery by A. Gessain et al. (J. Infect. Disease 1988; 1226-1234) of neurological syndromes associated with the HTLV-1 virus, known originally as an agent of T-cell leukemias in adults, has led several authors, such as H. Koprowski et al. (Nature 1985; 318, 154), M. Ohta et al. (J. Immunol. 1986; 137, 3440), Reddy et al. (Science 1989; 243, 529), S. J. Greenberg et al. (Proc. Natl. Acad. Sci. USA 1989; 86, 2878), J. H. Richardson et al. (Science 1989; 246, 821), S. L. Hauser et al. (Nature 1986; 322, 176) and A. Karpas et al. (Nature 1986; 322, 177), to investigate an involvement of this human retrovirus in MS, but without success or with results which suggest cross-reactions.
There is furthermore an animal model which is very close to MS and is induced by a retrovirus: the MAEDI-VISNA virus of sheep. It is known that natural infection by this virus causes an ovine disease similar to MS, as reported by Johnson R. T. (Rev. Infect. Dis. 1985; 7, 66-67), Narayan O. and Cork L. C. (Rev. Infect. Dis. 1985; 7, 89-98) and Nathanson N. et al. (Rev. Infect. Dis. 1985; 7, 75-82). Experimental infection of sheep by intraventricular inoculation of neurovirulent strains of the Visna virus has allowed the responsibility of this virus in the origin of this demyelinizing infection of sheep to be established. As explained by Nathanson N. et al. (Rev. Infect. Dis. 1985; 7, 75-82), Hoffman P. M. and Panitch H. S. ("Handbook of Clinical Neurology, 12; Viral Diseases" R. R. McKendall, ed., Elsevier Science Publishing, Amsterdam, 1989, 453-466) and A. Haase (Nature 1986; 322, 130-136), it differs slightly from natural infection, but nevertheless remains close to MS. It is moreover interesting to note that in all the works carried out on this subject by the abovementioned authors, the Visna virus is found in the cells of the plexus choroideus of the brain of infected sheep, which constitutes a site of dormancy and occasional replication of the Visna provirus; the location of these cells at the cephalorrachidian blood/fluid boundary certainly explains this phenomenon.
All these results argue in favor of the role of an unknown retrovirus in MS.
Works by H. Perron et al. (Res. Virol. 1989; 140, 551-561, and "Current concepts in multiple sclero
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K. G. Warren
Perron Herve
Seigneurin Jean-Marie
Bio Merieux
Housel James C.
Minnifield N. M.
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