Abstract: The present invention relates, e.g., to a method for inhibiting infectivity of a lentivirus (e.g., a lentivirus which expresses a Viral infectivity factor (Vif) protein), such as, e.g., SIV, SHIV and/or HIV, comprising contacting a cell which is producing the virus with an antiviral-effective amount of a membrane-permeable Zinc (Zn) chelator, wherein the antiviral-effective amount of the Zn chelator does not substantially inhibit proteins in the cell which contain Zn-binding motifs other than lentivirus Vif. Kits and pharmaceutical compositions are also disclosed, as is a method for identifying inhibitors of lentiviruses that target a specific zinc-binding motif of the lentivirus Vif protein.

Abstract: Cullin5 (Cul5) E3 ubiquitin ligase is shown to be linked with the heat shock protein 90 (Hsp90) chaperone complex. Hsp90 participates in the folding of its client proteins into their functional conformation. Many Hsp90 clients have been reported to be aberrantly expressed in a number of cancers. Cul5 is shown to interact with members of the Hsp90 chaperone complex as well as the Hsp90 client, ErbB2, Cul5 is recruited to the site of ErbB2 at the plasma membrane and subsequent induction of polyubiquitination and proteasomal degradation. Cul5 is also involved in the regulation of another Hsp90 client, Hif-1? Cul5 degradation of ErbB2 occurs independently of ElonginB-ElonginC function. The involvement of Cul5 in Hsp90 client regulation has implications in the effectiveness of Hsp90 targeted chemotherapy, which is currently undergoing clinical trials. The link between Cul5 and Hsp90 client regulation may represent an avenue for cancer drug development.

Abstract: The present invention relates, e.g., to a method for inhibiting infectivity of a lentivirus (e.g., a lentivirus which expresses a Viral infectivity factor (Vif) protein), such as, e.g., SIV, SHIV and/or HIV, comprising contacting a cell which is producing the virus with an antiviral-effective amount of a membrane-permeable Zinc (Zn) chelator, wherein the antiviral-effective amount of the Zn chelator does not substantially inhibit proteins in the cell which contain Zn-binding motifs other than lentivirus Vif. Kits and pharmaceutical compositions are also disclosed, as is a method for identifying inhibitors of lentiviruses that target a specific zinc-binding motif of the lentivirus Vif protein.

Abstract: The importance of interaction between TSG101 and Vps28 in the release of HIV-1 and other viruses is disclosed. Suppressing or interfering in this interaction may inhibit HIV-1 virion release from infected cells. Agents that modulate this interaction include antibodies that bind to Vps28, polypeptides that bind to Vps28, and nucleic acids that may be used in gene therapy to interfere with the expression of wild type Vps28. Administration of such agents in vitro for screening and diagnostic purposes, and in vivo for diagnostic and therapeutic purposes, is disclosed.

Abstract: The present invention relates, e.g., to a method for inhibiting infectivity of a lentivirus (e.g., a lentivirus which expresses a Viral infectivity factor (Vif) protein), such as, e.g., SIV, SHIV and/or HIV, comprising contacting a cell which is producing the virus with an antiviral-effective amount of a membrane-permeable Zinc (Zn) chelator, wherein the antiviral-effective amount of the Zn chelator does not substantially inhibit proteins in the cell which contain Zn-binding motifs other than lentivirus Vif. Kits and pharmaceutical compositions are also disclosed, as is a method for identifying inhibitors of lentiviruses that target a specific zinc-binding motif of the lentivirus Vif protein.

Abstract: The invention provides methods and compositions based on the interaction of TSG101 and VPS28 proteins for treatment of viral infections, including HIV infections. The invention also provides TSG101-VPS28 based methods and compositions for evaluation and screening of drugs which can be used for treating viral infections.