1887

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 1, 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 1 infection was a separate event from the upregulation of ROS during the late phase while 1-mediated cell death occurred. The treatment of apocynin, a potential inhibitor of NADPH oxidase (NOX), inhibited establishment of the 1 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 results were further supported by an experiment which showed that the treatment of apocynin decreased viral titre in the 1-infected mouse brain and increased the lifespan of infected mice. This study provides the first and evidence on a mechanism for how ROS are involved in 1 retrovirus infection and 1-mediated neurodegenerative disease. Our findings focusing on the early phase of the 1 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.

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2013-10-01
2020-01-21
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