Article

Role of oxidative damage in the pathogenesis of viral infections of the nervous system.

Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
Histology and histopathology (Impact Factor: 2.24). 08/2005; 20(3):957-67.
Source: PubMed

ABSTRACT Oxidative stress, primarily due to increased generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), is a feature of many viral infections. ROS and RNS modulate the permissiveness of cells to viral replication, regulate host inflammatory and immune responses, and cause oxidative damage to both host tissue and progeny virus. The lipid-rich nervous system is particularly susceptible to lipid peroxidation, an autocatalytic process that damages lipid-containing structures and yields reactive by-products, which can covalently modify and damage cellular macromolecules. Oxidative injury is a component of acute encephalitis caused by herpes simplex virus type 1 and reovirus, neurodegenerative disease caused by human immunodeficiency virus and murine leukemia virus, and subacute sclerosing panencephalitis caused by measles virus. The extent to which oxidative damage plays a beneficial role for the host by limiting viral replication is largely unknown. An enhanced understanding of the role of oxidative damage in viral infections of the nervous system may lead to therapeutic strategies to reduce tissue damage during viral infection without impeding the host antiviral response.

0 Followers
 · 
77 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Oxidative tissue injury often accompanies viral infection, yet there is little understanding of how it influences virus replication. We show that multiple hepatitis C virus (HCV) genotypes are exquisitely sensitive to oxidative membrane damage, a property distinguishing them from other pathogenic RNA viruses. Lipid peroxidation, regulated in part through sphingosine kinase-2, severely restricts HCV replication in Huh-7 cells and primary human hepatoblasts. Endogenous oxidative membrane damage lowers the 50% effective concentration of direct-acting antivirals in vitro, suggesting critical regulation of the conformation of the NS3-4A protease and the NS5B polymerase, membrane-bound HCV replicase components. Resistance to lipid peroxidation maps genetically to transmembrane and membrane-proximal residues within these proteins and is essential for robust replication in cell culture, as exemplified by the atypical JFH1 strain of HCV. Thus, the typical, wild-type HCV replicase is uniquely regulated by lipid peroxidation, providing a mechanism for attenuating replication in stressed tissue and possibly facilitating long-term viral persistence.
    Nature Medicine 07/2014; DOI:10.1038/nm.3610 · 22.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine the involvement of oxidative stress in the pathogenesis of acute encephalopathy associated with human herpesvirus-6 (HHV-6) infection, we measured the levels of oxidative stress markers 8-hydroxy-2'-deoxyguanosine (8-OHdG) and hexanoyl-lysine adduct (HEL), tau protein, and cytokines in cerebrospinal fluid (CSF) obtained from patients with HHV-6-associated acute encephalopathy (HHV-6 encephalopathy) (n = 16) and complex febrile seizures associated with HHV-6 (HHV-6 complex FS) (n = 10). We also examined changes in CSF-8OHdG and CSF-HEL levels in patients with HHV-6 encephalopathy before and after treatment with edaravone, a free radical scavenger. CSF-8-OHdG levels in HHV-6 encephalopathy and HHV-6 complex FS were significantly higher than in control subjects. In contrast, CSF-HEL levels showed no significant difference between groups. The levels of total tau protein in HHV-6 encephalopathy were significantly higher than in control subjects. In six patients with HHV-6 infection (5 encephalopathy and 1 febrile seizure), the CSF-8-OHdG levels of five patients decreased after edaravone treatment. Our results suggest that oxidative DNA damage is involved in acute encephalopathy associated with HHV-6 infection.
    Mediators of Inflammation 09/2014; 2014:564091. DOI:10.1155/2014/564091 · 2.42 Impact Factor
  • Source
    Dataset: 591290

Preview

Download
0 Downloads
Available from