Chemokine variants and methods of use

An isolated polynucleotide which encodes an amino acid sequence as set forth in SEQ ID NO:2.

A method for identifying a compound which modulates Dipeptidyl peptidase IV (DPPIV)-mediated chemokine processing comprising:

• a) incubating components comprising the compound, DPPIV and a chemokine under conditions sufficient to allow the components to interact;
• and
• b) determining the N-terminal amino acid sequence of the chemokine before and after incubating in the presence of the compound.

A method of inhibiting membrane fusion between HIV and a target cell or between an HIV-infected cell and a CD4 positive uninfected cell comprising contacting the target or CD4 positive cell with a fusion-inhibiting effective amount of the polypeptide of SEQ ID NO:2.

A method of treating a subject having or at risk of having an HIV infection or disorder, comprising administering to the subject, a therapeutically effective amount of a polypeptide of SEQ ID NO:2, wherein the polypeptide inhibits cell-cell fusion in cells infected with HIV.

A method of treating a subject having an HIV-related disorder associated with expression of CCR5 comprising administering to an HIV infected or susceptible cell of the subject, a polypeptide of SEQ ID NO:2 or a nucleic acid sequence encoding the polypeptide of SEQ ID NO:2 or other variant chemokine.

A pharmaceutical composition comprising the polypeptide of SEQ ID NO:2 in a pharmaceutically acceptable carrier.

A pharmaceutical composition comprising CD26 polypeptide in a pharmaceutically acceptable carrier.

A method for producing a variant chemokine having an activity different from the activity of the wild-type chemokine, comprising contacting the wild-type chemokine with an N-terminal processing effective amount of Dipeptidyl peptidase IV (DPPIV), thereby truncating the chemokine and producing a variant chemokine.

A method for inhibiting HIV-1 replication in a host cell susceptible to HIV-1 infection, comprising contacting the cell or the host with an effective amount of Dipeptidyl peptidase IV (DPPIV) enzyme such that macrophage-derived chemokine (MDC) is cleaved to produce truncated MDC, thereby providing antiviral activity and inhibiting HIV-1 replication.

A method for inhibiting Dipeptidyl peptidase IV (DPPIV)-mediated chemokine processing comprising contacting DPPIV with an inhibiting effective amount of a compound which inhibits DPPIV expression or activity.

A method for inhibiting an allergic or inflammatory reaction in a subject, comprising administering to the subject an effective amount of Dipeptidyl peptidase IV (DPPIV) enzyme such that a chemokine is cleaved to produce a truncated chemokine, thereby inhibiting an allergic or inflammatory reaction.

A method for accelerating angiogenesis or wound healing in a subject, comprising administering to the subject an effective amount of an inhibitor of Dipeptidyl peptidase IV (DPPIV) enzyme activity or gene expression or a DPPIV-insensitive chemokine, such that chemokine processing is inhibited, thereby accelerating angiogenesis or wound healing.

A method for inhibiting HIV-1 replication in a host cell susceptible to HIV-1 infection, comprising contacting the cell or the host with an effective amount of Dipeptidyl peptidase IV (DPPIV) enzyme such that RANTES is cleaved to produce truncated RANTES, thereby providing antiviral activity and inhibiting HIV-1 replication.

Antibodies which bind to wild-type chemokine but not to DPPIV-truncated chemokine.

Antibodies which bind to DPPIV-truncated chemokine but not to wild-type chemokine.