The Influence of Nutrition on Influenza Virus Infection

流感病毒感染每年在世界范围内造成大量的发病率和死亡率。流感病毒因改变其基因组而臭名昭著，因此不断将新的流感病毒株引入人口。由于基因组的变化，感染上一年的流感毒株并不能保证对新毒株的免疫保护。因此，流感研究人员每年都试图预测可能出现的新流感毒株，以生产疫苗。我们之前对柯萨奇病毒(一种RNA病毒)的研究表明，宿主的营养状况会影响病毒的基因组。我们能够证明，当小鼠感染无毒柯萨奇病毒B3株(CVB3/0)时，喂食营养充足的食物的小鼠不会患上心肌炎。然而，当小鼠被喂养缺乏硒(Se)或维生素E的食物时，它们现在患上了感染正常健康的CVB3/0病毒后的心肌炎。这种毒力的变化被发现是由于病毒中发生的突变，这种突变在缺乏硒的动物身上复制。我们发现，从缺硒小鼠分离的病毒中有6个核苷酸发生了变化。在Se充足的小鼠体内复制的病毒没有变化。这些变化都与病毒的强毒株有关。这是首次证明一种特定的营养缺乏会导致病毒基因组的变化，将无毒病毒转变为强毒病毒。这项建议旨在将我们对柯萨奇病毒的研究扩展到另一种RNA病毒，即流感病毒。初步结果表明，流感病毒与柯萨奇病毒一样，在缺乏硒的宿主中复制时，会突变为更强的毒力基因。一旦这些突变发生在缺硒动物身上，即使是硒状态正常的小鼠也容易受到新突变的流感病毒毒力增加的影响。这项建议旨在确定诱导流感病毒变异的潜在机制(S)。这项工作将有助于进一步了解寄主的营养状况如何不仅影响寄主本身，还会影响病毒病原体。通过将我们对柯萨奇病毒的观察扩展到一种新的病毒系统，我们可以证明我们的发现并不是柯萨奇病毒独有的，而是可以在另一种RNA病毒中发生。这些发现指出了宿主在感染期间营养状况的重要性，并表明宿主的营养状况也可以通过直接影响病毒基因组而在新出现的传染病中发挥作用，这是一种以前未知的现象。

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.