The emergence of new, more pathogenic viruses necessitates elucidation of factors that promote viral evolution. Aging, a potential factor, is associated with increased susceptibility to viral infections. We used the enterovirus coxsackievirus B3 (CVB3) to investigate the effects of host age on pathogenicity and viral gene sequence. Old mice infected with a normally amyocarditic strain of CVB3, CVB3͞0, had significantly higher mean heart viral titers compared with CVB3͞0-infected adult mice. To determine whether a change in the CVB3͞0 viral population could contribute to the higher titers observed in the old infected mice, CVB3͞0 was passed once through an old or adult host and the changes in pathogenicity and viral genome were examined after subsequent infection of old or adult mice. Adult mice infected with CVB3͞0 that was passed through an old host (CVB3͞0 Old ) exhibited significantly higher heart viral titers, pathology, and weight loss than adult mice infected with either stock CVB3͞0 or CVB3͞0 passed through an adult host (CVB3͞0 Adult ). Sequence analysis of virus isolated from CVB3͞0 Old -infected mice revealed 13 specific and reproducible nucleotide changes. These changes result in a sequence that matches the virulent CVB3͞20 strain and are associated with promoting cardiovirulence. In contrast, we observed only one nucleotide change, low heart viral titers, and no heart and liver pathology in adult mice infected with CVB3͞0 Adult . These results demonstrate that the aged host promotes rapid selection of a pathogenic variant of CVB3 from an avirulent strain and introduces a host-virus paradigm for studies of viral infection in the aged.aging ͉ myocarditis ͉ oxidative stress ͉ pathology ͉ viral selection

Many nutrients can have significant impacts on immunocompetence during periods of deficiency and supplementation. Current evidence indicates a beneficial role of numerous vitamins on immunity, including vitamins E, B6, and B12. Of these three nutrients, the strongest evidence exists for vitamin E, which has been shown to improve cell‐mediated and humoral immunity in both animal and human studies. Vitamin E supplementation was found to reverse the age‐associated decline in immune response with levels above the current RDA. This increase in immune response can have benefits in elderly or other immunocompromised patients. Human and animal data indicate that both B6 and B12 play a critical role in nucleotide synthesis and subsequent cell growth. Therefore, insufficient levels of B6 and B12 would inhibit the immune system's ability to respond to pathogenic challenge. B6 deficiency impairs both cell‐mediated and humoral immunity in animals and humans, which is reversed following B6 supplementation. Clinical evidence suggests that B6 supplementation may improve immune function in patients with rheumatoid arthritis and HIV infection. Although few studies have been conducted with B12, limited evidence suggests a beneficial effect of B12 on immune function with HIV infection. More research is needed to elucidate clinical benefits and mechanisms of the immunostimulatory effect of these vitamins.