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.

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    • "These species in turn can regulate host inflammatory and immune responses as well as causing oxidative damage in nucleic acids and proteins and in lipid-containing structures to which, the nervous system, being cholesterol and poly-unsaturated lipidrich , is particularly susceptible [90]. Even during latent HSV1 infection (of mice) there is evidence of oxidative damage and of persistent inflammation, and it is suggested on the basis of detection of oxidation products in different types of cell, that not only the latently infected neurons but also uninfected neurons and glial cells are damaged [90]. However it should be mentioned that if a very low level persistent infection i.e., virus replication , were to occur, it might be below the limits of detection by convention techniques and therefore would not be distinguishable from latent infection. "
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    Journal of Alzheimer's disease: JAD 06/2008; 13(4):393-405. · 3.61 Impact Factor
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    • "For example, oxidative stress in chronic hepatitis C virus infection interferes with antiviral innate immune responses and exacerbates lung injury (Wang and Weinman, 2006). Tissue injury by oxidative stress is also associated with encephalitis caused by herpes simplex virus type 1 and reovirus, dementia caused by human immunodeficiency virus, and subacute sclerosing panencephalitis caused by measles virus (Steiner et al., 2006; Valyi-Nagy and Dermody, 2005). In addition to tissue injury, recent studies revealed that NO-induced oxidative stress accelerates viral mutation which may increase the heterogeneity of RNA viruses and lead to viral evolution under selective pressures (Akaike, 2001). "
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    • "Increased generation of ROS is intrinsic to viral infections and can be caused by direct effects of virus on cells and/or inflammatory responses of the host [90] [91] [93] [94]. NO and ROS, particularly O 2 − , rapidly form the reactive nitrogen oxide, peroxynitrite (ONOO − ), that may cause oxidation and nitration of amino acid residues of proteins or guanine of DNA, lipid peroxidation, and DNA cleavage, all of which can cause cellular dysfunction and injury leading to cell death [91] [93] [95]. Myeloperoxidase (MPO), eosinophil peroxidase (EPO), and lactoperoxidase (LPO) are members of the mammalian peroxidase superfamily and play specific and complementary roles in host defense through oxidative pathways [90,92,95–99]. "
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