Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1997-05-07
1998-09-29
Woodward, Michael P.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
435348, 4352523, 4353201, 4352351, 435365, 530350, 536 2372, 930224, 4241861, C12P 2102, C07K 1403, C12N 1538, C12N 510
Patent
active
058144862
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates generally to novel herpes simplex virus glycoprotein D molecules. More particularly, the present invention relates to variant glycoprotein D molecules which are capable of blocking infection of cells by herpes simplex virus.
BACKGROUND OF THE INVENTION
Herpes simplex viruses (HSV) are human pathogens which cause a variety of disease states including cold sores, eye and genital infections, life-threatening neonatal infections, and encephalitis. HSV is also capable of establishing latent infections in ganglia. The strains designated HSV-1 (oral) and HSV-2 (genital) are members of the family Herpesviridae and are classified in the subfamily alphaherpesvirinae and the genus simplex virus. The viruses have an enveloped double-stranded DNA genome of 150 kilobases (kb) including at least seventy-two open reading frames which encode at least eleven glycoproteins. The genomes of HSV-1 and HSV-2 exhibit extensive homology in regions which are known to encode proteins responsible for antigenic specificity and/or biological activity.
Upon infection, several viral glycoproteins act singly or in concert to bind HSV to a susceptible cell and trigger direct fusion between the virion envelope and the cell membrane. Glycoprotein D (gD) of HSV is a component of the virion envelope which plays an essential role in HSV entry into susceptible mammalian cells. The evidence to date suggests that gD binds to a cellular molecule following the initial interaction of HSV glycoproteins gC and gB with heparan sulfate proteoglycans. The interaction between gD and its receptor may stabilize the virus-cell complex prior to membrane fusion which is mediated by other essential glycoproteins such as gB, gH, and gL. See Sisk et al., J. Virol., 68(3): 766-775 (1994) and Tal-Singer et al., J. Virol., 69(7): 4471-4483 (1995). The nucleotide sequence of the Patton strain of HSV-1 gD (gD-1) (SEQ ID NO: 3) was first reported in Watson et al., Science, 218: 381-384 (1982). The strain 333 HSV-2 gD (gD-2) was described in Muggeridge et al., J. Virol., 64(8): 3617-3626 (1990). The nucleotide sequence of the strain 333 gD-2 gene is set out in SEQ ID NO: 14 herein.
The HSV glycoproteins have been the subject of intense research in development of vaccines useful in preventing or treating HSV infections. See especially, U.S. Pat. Nos. 4,709,011 issued Nov. 24, 1987; 4,762,708 issued Aug. 9, 1988; and 5,149,660 issued Sep. 22, 1992; all to co-inventors herein. In addition, significant effort has been expended in the development of anti-viral agents such as nucleoside analogues and interferons. Nucleoside analogues idoxuridine, trifluridine, vidarabine and acyclovir interfere with HSV genome replication. Interferons interfere with the translation of viral proteins.
While some clinical benefit in ameliorating the sequelae of HSV infection has been achieved by treatment with nucleoside analogues and interferons, therapy with both types of compounds can involve significant side effects. See Fields and Knipe, Eds., Fundamental Virology, Chapter 16, Raven Press, New York, N.Y. (1986). Patients treated with acyclovir, for example, may exhibit local inflammation at sites where the drug is administered, renal dysfunction, and encephalopathic changes. Moreover, HSV mutants resistant to acyclovir have been observed and suppression of recurrences ceases when (1984)!. Experience in the use of vidarabine has revealed neurologic toxicity. Patients treated with interferon may exhibit fever, fatigue, anorexia, weight loss, nausea and vomiting, bone marrow suppression, pain at injection sites, lymphadenopathy, and mild hair loss. Fibroblast interferon has also been reported to induce the formation of anti-interferon antibodies.
There thus exists a need in the art for additional products useful in preventing or treating HSV infection.
SUMMARY OF THE INVENTION
The present invention provides variant HSV gD molecules capable of preventing infection of cells by HSV-1 and/or HSV-2. Also provided are novel purified and iso
REFERENCES:
patent: 4709011 (1987-11-01), Cohen et al.
patent: 4762708 (1988-08-01), Cohen et al.
patent: 5149660 (1992-09-01), Cohen et al.
patent: 5654174 (1997-08-01), Cohen et al.
Finberg, R & Ertt, H. (1987) Use of anti-idiotypic antibodies as inmunizing antigen, pp. 7-11, Cold Spring Harbor Laboratory Publications, Cold Spring Harbor, New York 11724.
Cai et al., "Herpes Simplex Virus Type 1 ICPO Plays a Critical Role in the De Novo Synthesis of Infectiuos Virus following Transfection of Viral DNA," J. Virol., 63(11): 4579-4589 (1989).
Chiang et al. "Identification of Functional Regions of Herpes Simplex Virus Glycoprotein gD by Using Linker-Insertion Mutagenesis," J. Virol., 68(4): 2529-2543 (1994).
Cohen et al. "Expression of Herpes Simplex virus Type I Glycoprotein D Deletion Mutants in Mammalian Cells," J. Virol., 62(8): 1932-1940 (1988).
Fields and Knipe, Eds., Fundamental Virology, Chapter 16, Raven Press, New York, New York (1986).
Hill et al., "Trauma to the Skin Causes Recurrence of Herpes Simplex in the Mouse," J. gen. Virol., 39: 21-28 (1978).
Hill et al., "Adrenergically induced recurrent HSV-1 corneal epithelial lesions," Curr. Eye Res., 6(8): 1065-1071 (1987).
Johnson et al., "Soluble Forms of Herpes Simplex Virus Glycoprotein D Bind to a Limited Number of Cell Surface Receptors and Inhibit Virus Entry into Cells," J. Virol., 64(6): 2569-2576 (Jun. 1990).
Kunkel et al., "Rapid and Efficient Site-Specific Mutagenesis without Phenotypic Selection," Methods Enzymol., 154: 367-382 (1987).
Landolfi et al., "Baculovirus-expressed herpes simplex virus type 2 glycoprotein D is immunogenic and protective against lethal HSV challenge," Vaccine, 11: 407-414 (1993).
Ligas and Johnson, "A Herpes Simplex Virus Mutant in Which Glycoprotein D Sequences Are Replaced by .beta.-Galactosidase Sequences Binds to but Is Unable To Penetrate into Cells," J. Virol., 62(5): 1486-1494 (1988).
Long et al., "Glycoprotein D Protects Mice Against Lethal Challenge with Herpes Simplex Virus Types 1 and 2," Infect. Immun., 37(2): 761-764 (1984).
Martin et al., "Soluble Glycoprotein D Blocks Herpes Simplex Virus Type 1 Infection of Rat Eye," J. Virol., 66(9): 5183-5189 (Sep. 1992).
Metcalf et al., "Herpetic Keratitis in Athymic (Nude) Mice," Infect, Immun., 26(3): 1164-1171 (1979).
Muggeridge et al., "Identification of a Site on Herpes Simplex Virus Type I Glycoprotein D That Is Essential for Infectivity," J. Virol., 64(8): 3617-3626 (1990).
Remmington: The Science and Practice of Pharmacy, 19th Edition, Mack Publishing Co., Easton, PA (1995).
Rock and Fraser, "Detection of HSV-1 genome in central nervous system of latently infected mice," Nature, 302(7): 523-525 (1983).
Sisk et al., "High-Level Expression and Purification of Secreted Forms of Herpes Simplex Virus Type 1 Glycoprotein gD Synthesized by Baculovirus-Infected Insect Cells," J. Virol., 68(2): 766-775 (1994).
Stanberry et al., "Genital Herpes in Guinea Pigs: Pathogenesis of the Primary Infection and Description of Recurrent Disease," J. Infect. Dis., 146(3): 397-404 (Sep. 1982).
Stanberry, L.R., "Pathogenesis of Herpes Simplex Virus Infection and Animal Models for its Study," Current Topics in Microbiol. and Immuno., 179: 15-30 (1992).
Stevens, "Human Herpesviruses: a Consideration of the Latent State," Microbiol. Rev., 53(3): 318-332 (1989).
Stevens and Cook, "Latent Herpes Simplex Virus in Spinal Ganglia of Mice," Science, 173: 843-845 (1971).
Straus et al., "Supression of Frequently Recurring Genital Herpes, A Placebo-Controlled Double-Blind Trial of Oral Acyclovir," N. Eng. J. Med., 310(24): 1545-1550 (1984).
Tal-Singer et al., "Interaction of Herpes Simplex Virus Glycoprotein gC with Mammalian Cell Surface Molecules" J. Virol., 69(7): 4471-4483 (1995).
Tenser, R.B., "Intracerebral Inoculation of Newborn and Adult Mice with Thymidine Kinase-Deficient Mutants of Herpes Simplex Virus Type 1," J. Infect. Dis., 147: 956 (May 1983).
Tessier et al., "Enhanced secretion from insect cells of a foreign protein fused
Cohen Gary H.
Eisenberg Roselyn T.
Nicola Anthony
Competitive Technologies Inc.
Fuldner Rebecca A.
Woodward Michael P.
LandOfFree
Herpes simplex virus glycoprotein D variants does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Herpes simplex virus glycoprotein D variants, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Herpes simplex virus glycoprotein D variants will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-685451