Benign human enterovirus becomes virulent in selenium‐deficient mice

Abstract

Coxsackieviruses have been implicated as possible co-factors in the etiology of the selenium (Se)-responsive cardiomyopathy known as Keshan disease. Here we report that a cloned and sequenced amyocarditic coxsackievirus B3 (CVB3/0), which causes no pathology in the hearts of Se-adequate mice, induces extensive cardiac pathology in Se-deficient mice. CVB3/0 recovered from the hearts of Se-deficient mice inoculated into Se-adequate mice induced significant heart damage, suggesting mutation of the virus to a virulent genotype. We demonstrate the important role of host nutritional status in determining the severity of a viral infection.

The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities

“…Viral diseases are affected by Se levels, and one disease for which Se supplementation to overcome Se-deficiency has been particularly effective as a preventive modality is Keshan disease (270), a myocarditis mainly occurring in regions of China with low soil Se. A suspected co-factor in the etiology of Keshan disease is coxsackievirus B3 (CVB3), which may become more virulent under low Se status in the infected host (17). In fact, changes in the virus itself have been more clearly established as a mechanism by which Se-deficiency promotes the development of Keshan disease than impaired immunity or chronic inflammation (119).…”

Viral Myocarditis

“…Intriguingly, a normally avirulent (noncardiovirulent) CVB3 (CVB3/0) has been found to acquire virulence in selenium-deficient mice after intraperitoneal infection. 28 Subsequently, 6 nucleotide changes have been identified in the now virulent CVB3 genome isolated from the avirulent CVB3/0 -infected selenium-deficient mice. 29 The mutated 6 nucleotides in the virulent CVB3 have completely corresponded with nucleotides found in known virulent CVB3 (CVB3/M1, CVB3/20) genomes.…”

Reactive oxygen species and nitric oxide in viral diseases

“…Most remarkable is the observation that mice made deficient in selenium and vitamin E may be killed by Coxsackie virus strains, which are harmless in selenium-sufficient animals. The unexpected observation that a number of animals inoculated with an attenuated strain produced a virulent strain capable of also killing animals sufficient in selenium and vitamin E suggests that the antioxidant status of a host may even influence viral evolution by as yet unknown mechanisms (72)(73)(74). Antioxidants, particularly when given in a blend and at proportions present in a balanced diet of fruits and vegetables, are not toxic, and no untoward effects are to be expected from their use as a supportive adjunct to conventional therapy in viral diseases.…”