Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Reexamination Certificate
1997-09-12
2001-04-03
Spector, Lorraine (Department: 1646)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
C435S320100, C435S325000, C435S252300, C435S254110, C536S023500, C536S023100, C530S350000
Reexamination Certificate
active
06210921
ABSTRACT:
BACKGROUND OF THE INVENTION
Adenoviruses and coxsackieviruses are common human pathogens. Adenoviruses, non-enveloped DNA viruses, are a major cause of respiratory and gastrointestinal infections (Horwitz,
In Virology
, 3rd edition: 2149-2171 1996), as well as infections of the heart (Martin et al.,
Circulation
, 90: 330-339 1994). In addition to their importance as disease agents, adenoviruses have been adapted for use as vectors for vaccination and gene therapy (Kremer and Perricaudet,
British Medical Bulletin
, 51: 31-44, 1995). Coxsackie B viruses, non-enveloped RNA viruses belonging to the picornavirus family, cause non-specific febrile illnesses and meningoencephalitis (Melnick,
In Virology
, 3rd edition: 655-712, 1996), and are the viruses most frequently identified in acute infections of the heart (Grist and Reid,
In Viral Infection of the Heart
, 23-31, 1993; Savoia and Oxman,
In Principles and Practice of Infectious Diseases
, 4th edition, 799-813, 1995). Coxsackie B viruses are also implicated in acute pancreatitis (Imrie et al.,
Gut
, 18: 53-56, 1977) and as triggering-agents in childhood-onset diabetes (Yoon et al.,
New England Journal of Medicine
, 300: 1173-1179, 1979; Clements et al.,
Lancet
, 346: 221-223, 1995).
Viruses initiate infection by attaching to cell surface receptors, and tissue-specific expression of receptor molecules is an important determinant of virus tropism. Adenovirus attachment to cells is mediated by elongated fibers projecting from each of the 12 vertices of the icosahedral viral capsid. Isolated soluble fibers bind cells with high affinity, and block virus attachment and infection, demonstrating that fiber attachment to a cell surface receptor is a critical event in infection (Philipson et al.,
J. Virology
, 49: 635-640, 1968; Defer et al.,
J. Virology
, 64: 3661-3673, 1990; Wickham et al.,
Cell
, 73: 309-319, 1993). Human adenoviruses are grouped on the basis of their ability to agglutinate erythrocytes. Competition experiments suggest that adenoviruses 2 and 5 (members of agglutination group C) share a common cellular receptor (Philipson et al.,
J. Virology
, 49: 635-640, 1968; Defer et al.,
J. Virology
, 64: 3661-3673, 1990), distinct from the receptor used by group B viruses such as adenovirus 3 (Defer et al.,
J. Virology
, 64: 3661-3673, 1990; Stevenson et al.,
J. Virology
, 69: 2850-2857, 1995) or 35. Although a number of cellular proteins associate with adenovirus on affinity columns (Hennache and Boulanger,
Biochemical Journal
, 166: 237-247, 1977; Svensson et al.,
J. Virology
, 38: 70-81, 1981) or in virus overlay blot assays (Defer et al.,
J. Virology
, 64: 3661-3673, 1990), the cellular molecules responsible for fiber-mediated adenovirus attachment have not been identified.
Twenty years ago, it was demonstrated that adenovirus 2 or its fibers compete with coxsackievirus B3 for a cell surface attachment site, suggesting that these unrelated viruses share a receptor protein (Lonberg-Holm et al.,
Nature
, 259: 679-681, 1976). More recently, coxsackie B viruses have been shown to interact with at least two cell-surface proteins (Reagan et al.,
J. Virology
, 49: 635-640, 1984), Decay accelerating factor (DAF, CD55) serves as an attachment receptor for some coxsackie B virus strains (Bergelson et al.,
J. Virology
, 69: 1903-1906, 1995; Shafren et al.,
J. Virology
, 69: 3873-3877, 1995). Expression of human DAF on rodent cells permits these strains to bind, but not to replicate, suggesting that additional factors may be required for infection.
A second 45-50 kD putative receptor molecule forms a detergent-stable complex with coxsackieviruses B3 and B4 (Mapoles et al.,
J. Virology
, 55: 560-566, 1985; Hsu et al.,
In New Aspects of Positive-Strand RNA Viruses
, 271-277, 1990). A monoclonal antibody raised against this complex is reported to protect cells from infection by all six coxsackie B serotypes (Hsu et al.,
J. Virology
, 62: 1647-1652, 1988), consistent with the observation that all six serotypes compete for a single cell surface receptor (Crowell and Tomko,
In Cellular Receptors for Animal Viruses
, 75-99, 1994).
SUMMARY OF THE INVENTION
This invention pertains to isolated nucleic acid molecules (e.g., cDNAs) comprising a nucleotide sequence encoding a coxsackievirus and adenovirus receptor protein, CAR, as well as nucleic acid fragments suitable as hybridization probes for the detection of CAR encoding nucleic acid (e.g, mRNA). Another aspect of the invention pertains to isolated or purified CAR protein and biologically active fragments thereof. Still yet another aspect of the invention pertains to recombinant expression vectors containing the nucleic acid molecules of the invention and host cells into which such recombinant expression vectors have been introduced. In one embodiment, such a host cell is used to produce CAR protein by culturing the host cell in a suitable medium. If desired, CAR protein can be then isolated from the medium or the host cell. Another aspect of the invention pertains to modulation of the activity of CAR in the treatment of infection. In one embodiment, an antisense nucleic acid molecule is used to down-regulate CAR expression. In another embodiment, an antibody raised against the CAR protein is used to block CAR expression. Yet another aspect of the invention pertains to enhancing transduction, in particular adenovirus, transduction by initiating or increasing CAR expression in a host cell.
REFERENCES:
patent: 5942606 (1999-08-01), Lal
patent: WO 93/ 17041 (1993-09-01), None
Hillier et al, The WashU-Merck EST project, Genbank Accession No. W39780, May 15, 1996, and N31467, Jan. 10, 1996.*
Fujiwara et al., Otsuka cDNA project, Genbank Accession No. C16023, Sep. 1996.*
Genexpress, The Genexpress cDNA program, Genbank Accession No. Z44690, Sep. 1995.*
Bergelson et al., Science 275:1320-3, Feb. 1997.*
Tomko et al., PNAS 94:3352-6, 1997.*
Bergelson, J.M. et al., The Murine CAR Homolog is a Receptor for Coxsackie B Viruses and Adenoviruses,Journal of Virology72(1):1-5 (1998).
Bergelson, J.M. et al., Isolation of a Common Receptor for Coxsackie B Viruses and Adenoviruses 2 and 5,Science275:1320-1323(Feb. 28, 1997).
Hsu, K.L. et al., A Monoclonal Antibody Specific for the Cellular Receptor for the Group B Coxsackieviruses,Journal of Virology62(5):1647-1652 (1988).
Grist, N.R. and Reid D., Epidemiology of Viral Infections of the Heart, In:Viral Infections of the Heart,J. Banatvala, ed. (London: Edward Arnold), pp. 23-31 (1993).
Yoon, J. et al., Virus-Induced Diabetes Mellitus,New England Journal of Medicine300(21):1173-1179 (1979).
Woodruff, J.F., Viral Myocarditis,American Journal of Pathology,101:427-479 (1980).
Lerner, A.M. and Wilson, F.M., Virus Myocardiopathy,Prog. med. Virol.15:63-91 (1973).
Xu, R. et al., “Receptor Proteins on Newborn Balb/c Mouse Brain Cells for Coxsackievirus B3 are Immunologically Distinct from Those on HeLa Cells”,Virus Research,vol. 35, 323-40 (1995).
Bergelson Jeffrey M.
Finberg Robert W.
Horwitz Marshall S.
Lazar-Wesley Eliane
Spector Lorraine
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