Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage

Peña, José; Chen-Harris, Haiyin; Allen, Jonathan E.; Hwang, Mona; Elsheikh, Maher; Mabery, Shalini; Bielefeldt-Ohmann, Helle; Zemla, Adam T.; Bowen, Richard A.; Borucki, Monica K.

Analysis of these data shows that viral virulence increased with passage in mice and that the virulent phenotype may also persist upon passage to a second host species, although nutritional status of mice during passage influenced the phenotype. Although deep sequencing revealed the presence of persistent high-frequency variant genotypes in the viral population, only one non-synonymous change in the consensus sequences was detected by passage 10 in a majority of the animals regardless of diet group, polymerase residue N1124D. Thus, it seems likely that shifts in variant populations at the subconsensus level had an effect on virulence. This phenomenon has been observed in other RNA viruses (Domingo 1997; Akaike et al. 2000) indicating the importance of viral population dynamics in understanding mechanisms of viral emergence.