Identifying cellular genes crucial for the reactivation of Kaposi's sarcoma-associated herpesvirus latency
pmid: 16476973
Identifying cellular genes crucial for the reactivation of Kaposi's sarcoma-associated herpesvirus latency
Kaposi's sarcoma-associated herpesvirus (KSHV) is the latest addition to the long list of human herpesviruses. Reactivation of latent herpesvirus infections is still a mystery. It was demonstrated recently that the phorbol ester TPA was efficient in inducing a reactivation of KSHV infection in the S phase of the cell cycle. In the present study, flow cytometry-sorted, TPA-induced, KSHV-infected haematopoietic cells (BCBL-1) were used to analyse the expression profiles of cancer-related cellular genes in the S phase of the cell cycle compared with the G0/1 phase by using microarrays. Overall, the S phase of the cell cycle seems to provide KSHV with an apt environment for a productive lytic cycle of infection. The apt conditions include cellular signalling that promotes survivability, DNA replication and lipid metabolism, while blocking cell-cycle progression to M phase. Some of the important genes that were overexpressed during the S phase of the cell cycle compared with the G0/1 phase of TPA-induced BCBL-1 cells arev-mybmyeloblastosis (MYBL2), protein kinase-membrane associated tyrosine/threonine 1 (PKMYT1), ribonucleotide reductase M1 polypeptide (RRM1) and peroxisome proliferator-activated receptors delta (PPARD). Inhibition of PKMYT1 expression by the use of specific short interfering RNAs significantly lowered the TPA-induced KSHV lytic cycle of infection. The significance of these and other genes in the reactivation of KSHV is discussed in the following report. Taken together, a flow cytometry–microarray-based method to study the cellular conditions critical for the reactivation of KSHV infection is reported here for the first time.
- East Carolina University United States
- University of North Carolina System United States
Ribonucleoside Diphosphate Reductase, Tumor Suppressor Proteins, Gene Expression, Membrane Proteins, Herpesviridae Infections, Protein Serine-Threonine Kinases, Protein-Tyrosine Kinases, S Phase, Virus Latency, Genes, Cell Line, Tumor, Herpesvirus 8, Human, Humans, Tetradecanoylphorbol Acetate, Virus Activation, PPAR delta
Ribonucleoside Diphosphate Reductase, Tumor Suppressor Proteins, Gene Expression, Membrane Proteins, Herpesviridae Infections, Protein Serine-Threonine Kinases, Protein-Tyrosine Kinases, S Phase, Virus Latency, Genes, Cell Line, Tumor, Herpesvirus 8, Human, Humans, Tetradecanoylphorbol Acetate, Virus Activation, PPAR delta
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