The Influence of Nutrition on Influenza Virus Infection

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Infection with influenza virus causes a great deal of morbidity and mortality worldwide every year. Influenza virus is notorious for changing its genome, thus continually introducing new strains of influenza virus into the population. Because of the genomic changes, infection with an influenza strain from the previous year does not guarantee immune protection from a new strain. Thus, influenza researchers attempt each year to predict the new strain of influenza that may arise in order to produce a vaccine. Our previous work with coxsackievirus, an RNA virus, demonstrated that the nutritional status of the host could influence the genome of the virus. We were able to show that mice fed a nutritionally adequate diet did not develop myocarditis when infected with an avirulent strain of coxsackievirus B3 (CVB3/0). However, when the mice were fed a diet deficient in either selenium (Se) or vitamin E, they now developed myocarditis following infection with the normally benign CVB3/0. This change in virulence was found to be due to mutations that occurred in the virus that repliated in the Se- deficient animals. We found 6 nucleotides had changed in the virus isolated from the Se-deficient mice. No changes occurred in virus which replicated in the Se-adequate mice. These changes were all associated with virulent strains of the virus. This was the first demonstration of a specific nutritional deficiency causing changes in a viral genome, changing an avirulent virus to a virulent one. This proposal is designed to extend our study with coxsackievirus to another RNA virus, namely influenza virus. Preliminary results demonstrate that influenza virus, like coxsackievirus, mutates to a more virulent genotype when replicating in a Se-deficient host. Once these mutations occurred in the Se-deficient animals, even mice with normal Se status are susceptible to the increase virulence of the newly mutated influenza virus. This proposal is designed to determine the underlying mechanism(s) involved in inducing the influenza virus to mutate. This work will lead to a further understanding of how the nutritional status of the host can not only affect the host itself, but also the viral pathogen as well. By extending our observations with coxsackievirus to a new viral system, we can demonstrate that our findings are not unique to coxsackievirus, but rather can occur in another RNA virus. These findings point to the importance of host nutritional status during an infection and demonstrate that the nutritional status of the host can also play a role in emerging infectious diseases by having a direct effect on the genome of a virus, a previously unknown phenomenon.