title: ROS upregulation during the early phase of retroviral infection plays an important role in viral establishment in the host cell.
abstract: Recent studies suggest that low levels of reactive oxygen species (ROS) often modulate normal intracellular signalling pathways, determine cell fates and control cell proliferation. We found that infection of astrocytes with the neuropathogenic retrovirus ts1, a mutant of Moloney murine leukemia retrovirus, upregulated ROS at low levels during the early phase of infection. This upregulation of intracellular ROS with downregulation of NADPH levels during the early phase of ts1 infection was a separate event from the upregulation of ROS during the late phase while ts1-mediated cell death occurred. The treatment of apocynin, a potential inhibitor of NADPH oxidase (NOX), inhibited establishment of the ts1 virus in the host cell. These results suggested that ROS generated as a consequence of the activation of NOX may play an important role in the early events of the virus life cycle leading to the establishment of the virus in the host cell. The in vitro results were further supported by an in vivo experiment which showed that the treatment of apocynin decreased viral titre in the ts1-infected mouse brain and increased the lifespan of infected mice. This study provides the first in vitro and in vivo evidence on a mechanism for how ROS are involved in ts1 retrovirus infection and ts1-mediated neurodegenerative disease. Our findings focusing on the early phase of the ts1 retrovirus life cycle could provide a better understanding of retroviral life cycle, which may offer specific therapeutic targets for suppressing viral replication and alleviating neurodegenerative symptoms in a mouse model.
authors.affiliation: Department of Molecular Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Smithville, TX, USA.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Molecular Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Smithville, TX, USA.
authors.forename: Paul K Y
authors.initials: PKY
authors.lastname: Wong
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000821:virology*; D016923:Cell Death; D002460:Cell Line; D004279:DNA, Viral / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D008979:Moloney murine leukemia virus / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000098:Acetophenones; D004279:DNA, Viral; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; C056165:acetovanillone; D013482:Superoxide Dismutase; D019255:NADPH Oxidases