Compounds, methods of screening, and in vitro and in vivo uses involving anti-apoptotic genes and anti-apoptotic gene products

A method of screening for a compound that inhibits or diminishes the specific binding of a physiological molecule to at least one of human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M, or pUL37L in an in vitro binding assay, said method comprising:

• (a) combining a first composition, comprising a candidate compound, with a second composition comprising a physiological molecule that specifically binds to at least one of human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M, or pUL37L,
• (b) combining a third composition comprising at least one of human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M, or pUL37L, or a fragment thereof, or a homologue of the human cytomegalovirus polypeptide or fragment thereof, with the combination of (a), in an in vitro binding assay, and
• (c) detecting an inhibition or diminution in specific binding

A method of screening for a polypeptide that specifically binds to at least one of human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M, or pUL37L in a double transformation assay, said method comprising:

• (a) introducing into cells a first polynucleotide encoding a candidate polypeptide and a second polynucleotide encoding at least one human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M, or pUL37L, or a fragment thereof, or encoding a homologue of the human cytomegalovirus polypeptide or fragment thereof, in a double transformation assay;
• and
• (b) detecting specific binding.

A pharmaceutical composition comprising a therapeutically effective amount of a polypeptide having anti-apoptotic activity and a pharmaceutically suitable carrier, wherein said polypeptide is at least one human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M, pUL37L, or fragment thereof, or a homologue of the human cytomegalovirus polypeptide or fragment thereof, wherein the therapeutically effective amount is an amount that inhibits, diminishes or modulates anti-apoptotic activity.

A pharmaceutical composition comprising a therapeutically effective amount of a polynucleotide encoding a polypeptide having anti-apoptotic activity and a pharmaceutically suitable carrier, wherein said polynucleotide encodes at least one human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M, pUL37L, or fragment thereof, or encodes a homologue of the human cytomegalovirus polypeptide or fragment thereof, wherein the therapeutically effective amount is an amount that inhibits, diminishes or modulates anti-apoptotic activity.

A pharmaceutical composition comprising a therapeutically effective amount of a compound that binds specifically to a polypeptide having anti-apoptotic activity and a pharmaceutically suitable carrier, wherein said polypeptide is at least one human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M, pUL37L, or fragment thereof, or a homologue of the human cytomegalovirus polypeptide or fragment thereof, wherein the therapeutically effective amount is an amount that restores, induces or modulates anti-apoptotic activity.

A pharmaceutical composition comprising a therapeutically effective amount of a compound that binds specifically to a polynucleotide encoding a polypeptide having anti-apoptotic activity and a pharmaceutically suitable carrier, wherein said polynucleotide encodes at least one human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M, pUL37L, or fragment thereof, or encodes a homologue of the human cytomegalovirus polypeptide or fragment thereof, wherein the therapeutically effective amount is an amount that restores, induces or modulates anti-apoptotic activity.

An isolated or synthetic polypeptide having anti-apoptotic activity in cells, wherein said polypeptide comprises a human cytomegalovirus polypeptide other than pUL37L.

An isolated or synthetic polypeptide having anti-apoptotic activity in cells, wherein said polypeptide comprises human cytomegalovirus polypeptide pUL36 or pUL37M.

An isolated or synthetic polypeptide having anti-apoptotic activity in cells, wherein said polypeptide comprises a fragment of human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M or pUL37L.

An isolated or synthetic polypeptide having anti-apoptotic activity in cells, wherein said polypeptide comprises a sequence homologous to the amino acid sequence of pUL36, pUL37S, pUL37M or pUL37L.

An isolated or synthetic polypeptide having anti-apoptotic activity in a cell, wherein said polypeptide comprises a polypeptide encoded by UL36, and wherein the nucleotide sequence of UL36 is defined by nucleotides 49,776-48,246 of the HCMV AD169 genome.

An isolated compound that specifically prevents the binding of human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M, or pUL37L to a physiological molecule selected from the group consisting of FADD, caspase 3, Apaf-1, Bcl-xL, Bcl-2, Bak, ICE, Bax, BNIP-3, ANT and caspase 8 in its pro- or activated form.

An isolated compound that specifically prevents the binding of one or more fragment of human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M, or pUL37L to a physiological molecule selected from the group consisting of FADD, caspase 3, Apaf-1, Bcl-xL, Bcl-2, Bak, ICE, Bax, BNIP-3, ANT and caspase 8 in its pro- or activated form.

An isolated compound that specifically prevents the binding of one or more homologue of human cytomegalovirus polypeptide pUL36, pUL37S, pUL37M, or pUL37L to a physiological molecule selected from the group consisting of FADD, caspase 3, Apaf-1, Bcl-XL, Bcl-2, Bak, ICE, Bax, BNIP-3, ANT and caspase 8 in its pro- or activated form.

An isolated or synthetic antibody that binds to at least one of pUL36, pUL37S, pUL37M, or pUL37L, or a fragment or homologue thereof.