Oxidative stress is produced during viral infections and contributes to the pathology of the disease. Nutritional deficiencies can exacerbate the problem (reviewed in Beck and Levander, 1998). The Coxsackie B3 virus, which is implicated in the pathology of Keshan disease, mutates to a more cardiotoxic form when passaged through Se-deficient mice (see Beck, 1999). This seems to be a common theme for RNA viruses and it has been proposed that the oxidizing environment of an Se-deficient host may contribute to faster mutation of the viral genome (Beck et al., 1995). These viruses lack proofreading capability and this contributes to their high mutation rates. Beck and Levander (1998) have noted that the severe forms of the influenza virus, demonstrating a large degree of antigenic drift, have evolved in Se-deficient parts of China and that HIV is thought to have evolved in areas of Central Africa where Se intake is very low. The importance of selenoenzymes for anti-viral protection was demonstrated in experiments where mice were fed gold thioglucose or gold sodium thiomalate, which inhibit selenocysteine residues. In these animals, injection with normally non-lethal Semliki Forest virus or Sindbis viruses was fatal (Beck and Levander, 1998). Furthermore, injection of non-virulent Coxsackie B3 virus into GPX knockout mice led to mutation to a more virulent strain (Beck, 1999).
The long terminal repeat of HIV controls replication and is activated by binding of NFkB, which is regulated by the cell redox state and oxidative stress. TNF-a stimulates NFkB activation in T-cells. As we have described, Se compounds can inhibit TNF-a release. An inverse correlation between plasma Se concentration, red-cell GPX activity and the progression of acquired immune deficiency syndrome (AIDS) has been shown (reviewed in Chen et al., 1997; McKenzie et al., 2002). In culture, Se supplementation of HIV-infected monocytes and CD4+ T-cells inhibits TNF-a-induced viral replication (Hori et al., 1997). Thus, it seems that Se may be useful in the treatment of AIDS (Chen et al., 1997). Dietary Se supplements have been used for the treatment of hepati-tis-B-induced liver cancer in China. The incidence of hepatitis-B-virus-induced liver cancer in humans decreased in a previously Se-deficient, hepatitis-B+ population given Se supplements of 200 ^g day-1.
Viruses illustrate the importance of the GPX system in protection from ROS. Several different viral genomes (HIV, Ebola, molluscum and hepatitis C) encode GPX-like molecules (Zhang et al., 1999). This presumably protects them against the ROS produced by host phagocytes.
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