Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage
Patent
1991-08-09
1993-10-26
Nucker, Christine M.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving virus or bacteriophage
435 8, 435 724, 435239, 43524026, C12Q 170
Patent
active
052565343
ABSTRACT:
The present invention relates to a unique physiologic model of chronic human immunodeficiency virus type-1 (HIV-1) infection. In particular, the present invention relates to a chronically infected promyelocyte cell line harboring a single integrated provirus. Unlike other models of chronic infection, the cell line of the present invention remain CD4.sup.+ under normal culture conditions during which <10% of the cells constitutively express HIV-1 proteins. However, when treated with tumor necrosis factor-alpha (TNF-.alpha.), the cell line dramatically increased (>35-fold) HIV-1 expression and rapidly down-modulated surface CD4, as >95% of the cells became HIV-1.sup.+. These results with the new OM-10.1 cell line demonstrate that CD4 surface expression can be maintained during chronic infection and is critically dependent upon the state of viral activation; that CD4-gp160/120 intracellular complexing is responsible for CD4 down-modulation; and that protein kinase pathways function not only in the primary induction of latent HIV-1 but are also involved in maintaining the state of viral activation.
REFERENCES:
Clouse et al: Monokine Regulation . . . Human T cell clone (TR) vol. 142, J. Immunol Jan. 1989 pp. 431-438.
Folks et al: Infection & Replication . . . Bone Marrow (UR) Science vol. 242 pp. 919-922 Nov. 1988.
Stedman's Medical Dictionary, 25th Ed., p. 1276 (1990).
Thomas M. Folks, et al., Biological and Biochimical Characterization of a Cloned Leu-3.sup.- Cell Surviving Infection with the Acquired Immune Deficiency Syndrome Retrovirus, vol. 164, Jul. 1986 280-290.
Thomas M. Folks, et al., Cytokine-Induced Expression of HIV-1 in a Chronically Infected Promonocyte Cell Line. vol. 238.
Thomas M. Folks, et al., Characterization of a Promonocyte Clone Chronically Infected with HIV and Inducible by 13-Phorbol-12-Myristate Acetate, vol. 140, 1117-1122, No. 4, Feb. 15, 1988.
M. I. Bukrinsky, et al., Quiescent T Lymhocytes as an Inducible Virus Reservoir in HIV-1 Infection. 10 Oct. 1991.
Butera Salvatore T.
Folks Thomas M.
Perez Victor L.
Nucker Christine M.
Rucker Susan S.
Stucker Jeffrey
The United States of America as represented by the Department of
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