title: Chloroquine inhibits lytic replication of Kaposi's sarcoma-associated herpesvirus by disrupting mTOR and p38-MAPK activation.
abstract: Lytic infection is essential for the persistent infection and pathogenesis of Kaposi's sarcoma-associated herpesvirus (KSHV), and inhibiting KSHV lytic replication may effectively prevent the occurrence of KSHV-related diseases. Chloroquine (CQ), a well-known antimalarial drug and autophagy inhibitor, exerts broad-spectrum antiviral effects and shows anti-cancer therapeutic potential. However, the ability of CQ and its derivatives to control infection of oncogenic γ-herpesvirus remains undefined. Here we reveal that CQ suppresses KSHV lytic gene expression and virion production, and shows cytotoxicity toward KSHV lytically infected B cells at clinically acceptable doses. CQ suppresses mTOR and p38-MAPK pathway activation during KSHV lytic replication but not latent infection. Furthermore, CQ blocks Epstein-Barr virus (EBV) lytic replication via a distinct mechanism that is invoked to block virion production but does not affect viral gene expression. These results suggest that CQ is an effective antiviral drug against KSHV lytic infection. Our findings indicate that CQ treatment should be considered for controlling KSHV-related diseases, particularly for primary use in co-infection of KSHV with malaria.
authors: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors: Mengtian
authors: M
authors: Yang
authors: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors: Lu
authors: L
authors: Huang
authors: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China. Electronic address: lixjuan3@mail.sysu.edu.cn.
authors: Xiaojuan
authors: X
authors: Li
authors: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, China. Electronic address: kuangersh@mail.sysu.edu.cn.
authors: Ersheng
authors: E
authors: Kuang
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D002738:Chloroquine; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Chloroquine; Kaposi's sarcoma-associated herpesvirus; Lytic replication; mTOR; p38-MAPK