The United States of America, As Represented by the Secretary, Department of Health and Human Services

The United States of America As Represented by the Department of Health

Emory University

Salvatore T Butera

Thomas M Folks

Bernard Moss

Harriet L Robinson

Ted M Ross

Linda S Wyatt

Rama Rao Amara

James Smith

John E Coligan

Dennis Ellenberger

James W Critchfield

Victor L Perez

James M Smith

Jian Hua

Rick Arthur Bright

Patricia Earl

We have developed DNA and viral vectors that can be used, alone or in combination, as a vaccine against one HIV clade, subtype, or recombinant form of HIV or against multiple HIV clades, subtypes, or recombinant forms. Moreover, the vectors can encode a variety of antigens, which may be obtained from one clade or from two or more different clades, and the antigens selected and/or the manner in which the vectors are formulated (e.g., mixed) can be manipulated to generate a protective immune response against a variety of clades (e.g., the clades to which a patient is most likely to be exposed; with the proportions of the components of the vaccine tailored to the extent of the patient's risk to a particular clade or clades).

Compositions and methods for generating an immune response

The present invention comprises methods and compositions for treating viral infection by inhibiting the activity of host cellular enzymes. More specifically, methods and compositions comprising casein kinase II inhibitors and various related compounds such as precursors, analogs, metabolites and hydrolysis products that inhibit cellular proteins and thus viral replication are provided.

Methods and compositions for inhibition of viral replication

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 &lt;10% of the cells constitutively express HIV-1 proteins. However, when treated with tumor necrosis factor-alpha (TNF-.alpha.), the cell line dramatically increased (&gt;35-fold) HIV-1 expression and rapidly down-modulated surface CD4, as &gt;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.

CD4.sup.+, latently HIV-1-infected hematopoietic progenitor cells

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Stockbridge, GA, United States of America

Salvatore T Butera