Previous work from our laboratory has demonstrated that infection with infl
uenza A/Bangkok/1/79 (H3N2), a relatively mild strain of the virus, caused
much more severe pneumonitis in selenium (Se)-deficient mice than in Se-ade
quate mice. Here we report that the increased virulence observed in the Se-
deficient mice is due to mutations in the influenza virus genome, resulting
in a more virulent genotype. Most of the mutations occurred in the gene fo
r the M1 matrix protein, an internal protein that is thought to be relative
ly stable. A total of 29 nucleotide changes were observed in this gene, and
all 29 changes were identical in three separate isolates taken from three
different Se-deficient mice. In contrast, only one to three mutations were
seen in the genes for the hemagglutinin or neuraminidase proteins, surface
antigens that are known to be highly variable. Once the mutations have occu
rred, even hosts with normal nutritional status are susceptible to the newl
y virulent strain. This work, in conjunction with our earlier work with cox
sackievirus, shows that specific nutritional deficiencies can have a profou
nd impact on the genome of RNA viruses. Poor nutritional status in the host
may contribute to the emergence of new viral strains.