title: Rapamycin does not inhibit human cytomegalovirus reactivation from dendritic cells in vitro.
abstract: Human cytomegalovirus (HCMV) infection and reactivation are a major cause of morbidity in immune-suppressed patients. Interestingly, epidemiological studies have shown that patients administered the mammalian target of rapamycin (mTOR) inhibitor, sirolimus (rapamycin), exhibit more favourable outcomes, suggestive of activity against HCMV in vivo. Given its relative lack of activity against lytic infection, it is postulated that rapamycin inhibits HCMV reactivation. Here, we showed that rapamycin administered acutely or chronically has little impact on induction of immediate early (IE) gene expression in experimentally latent dendritic cells or cells from naturally latent individuals. Furthermore, we extended these observations to include other inhibitors of mTORC1 and mTORC 2, which similarly have minimal effects on induction of IE gene expression from latency. Taken together, these data suggest that favourable outcomes associated with sirolimus are attributable to indirect effects that influence HCMV reactivation, rather than a direct mechanistic action against HCMV itself.
authors.affiliation: Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Glover
authors.affiliation: Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Verity G
authors.initials: VG
authors.lastname: Kew
authors.affiliation: Institute of Immunity & Transplantation, Royal Free Hospital, University College London, Hampstead, London NW3 2PF, UK.|Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Reeves
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000821:virology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020123:Sirolimus / Q000494:pharmacology*; D014775:Virus Activation / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D020123:Sirolimus