CMV gene products promote cancer stem cell growth
The disclosure relates generally to compositions and methods useful for inhibiting the infection and propagation of viral particles, particularly members of the Herpesviridae family, and more particularly to cytomegalovirus (CMV) and methods of treating diseases and disorders, including cell proliferative disorders, associated with CMV infection.
1. A method of inhibiting the proliferation, growth and/or migration of a glioblastoma cell infected with cytomegalovirus in a subject comprising administering to the cell an inhibitor of a cytomegalovirus IE1 gene, comprising a duplex of inhibitory nucleic acids comprising SEQ ID NOS: 6 and 7, wherein the duplex of inhibitory nucleic acids inhibits the expression of the IE1 polypeptide encoded by the IE1 gene.
2. The method of claim 1 further comprising administering to the cell an inhibitor of cytomegalovirus US28 and/or an inhibitor of cytomegalovirus pp71, wherein the inhibitors of US28 and pp71 are inhibitory nucleic acids.
3. The method of claim 2 wherein the inhibitors of US28 and pp71 are siRNA or ribozyme molecules.
4. A method of treating a cell proliferative disease or disorder comprising exposing a cell infected with CMV and having aberrant cell proliferation to at least one siRNA that targets RNA encoded by a CMV IE1 gene, wherein the at least one siRNA is a double stranded RNA (dsRNA) molecule comprising a 3′dTdT and a 5′ phosphate group, under conditions that permit induction of ribonucleic acid interference (RNAi), such that cell proliferation, growth and/or migration of the cell infected with CMV is inhibited and wherein the at least one siRNA comprises SEQ ID NOS:4 and 5, or SEQ ID NOS:6 and 7, or SEQ ID NOS: 4, 5, 6, and 7.
5. The method of claim 4 , wherein the at least one siRNA comprises at least two siRNAs, each targeted to an RNA encoded by a different target gene.
6. The method of claim 4 , wherein the at least one siRNA comprises three different siRNAs, each targeted to an RNA encoded by a different target gene.
7. The method of claim 5 or 6 , wherein the target genes include one or both of cytomegalovirus US28 and pp71.
8. The method of claim 4 , wherein the at least one siRNA is a double stranded RNA (dsRNA) molecule, each strand of which is about 18-29 nucleotides long.