title: Suppressive effects of sirtinol on human cytomegalovirus (hCMV) infection and hCMV-induced activation of molecular mechanisms of senescence and production of reactive oxygen species.
abstract: Substantial evidence suggests that chronic human cytomegalovirus (hCMV) infection contributes significantly to T-cell immunosenescence and adverse health outcomes in older adults. As such, it is important to search for compounds with anti-hCMV properties. Studies have shown that resveratrol, a sirtuin activator, suppresses hCMV infection. Here we report suppressive effects of sirtinol, a sirtuin antagonist, on hCMV infection and its cellular and molecular consequences. Human diploid fibroblast WI-38 cells were infected by hCMV Towne strain in the absence or presence of sirtinol. hCMV replication was measured using qPCR. Senescent phenotype was determined by senescence-associated β galactosidase (SA-β-Gal) activity. Expression of hCMV immediate early (IE) and early (E) proteins and senescence-associated proteins (pRb and Rb, p16(INK4), and p53) and production of reactive oxygen species (ROS) were assessed using standard laboratory assays. The results demonstrated that sirtinol suppressed hCMV infection as well as hCMV-induced activation of molecular mechanisms of senescence and ROS production. While underlying molecular mechanisms remain to be elucidated, these findings indicate sirtinol as a novel and potent anti-hCMV agent with the potential to be developed as an effective treatment for chronic hCMV infection and its cellular and molecular consequences that are important to ageing and health of older adults.
authors.affiliation: Zhejiang Provincial Key Laboratory of Geriatrics & Geriatrics Institute of Zhejiang Province, Zhejiang Hospital, 12 Lingyin Road, Hangzhou, Zhejiang Province 310013, China.
authors.forename: Genxiang
authors.initials: G
authors.lastname: Mao
authors.affiliation: Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
authors.forename: Huifen
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ding
authors.affiliation: Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Meng
authors.affiliation: Zhejiang Provincial Key Laboratory of Geriatrics & Geriatrics Institute of Zhejiang Province, Zhejiang Hospital, 12 Lingyin Road, Hangzhou, Zhejiang Province 310013, China. Electronic address: 1090983005@qq.com.
authors.forename: Guofu
authors.initials: G
authors.lastname: Wang
authors.affiliation: Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. Electronic address: sleng1@jhmi.edu.
authors.forename: Sean X
authors.initials: SX
authors.lastname: Leng
mesh_terms: D001549:Benzamides / Q000494:pharmacology*; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects*; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D009284:Naphthols / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014775:Virus Activation / Q000187:drug effects*
chemical_list: D001549:Benzamides; D009284:Naphthols; D017382:Reactive Oxygen Species; C439060:sirtinol
keywords: Reactive oxygen species; Sirtinol; hCMV infection; hCMV-induced cellular senescence