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.

To ascertain the effect of discrete mutations on the viral phenotype, clones were selected which represented the predominant genotypes present in the mutant spectra and were tested for virulence via mouse infections. Despite the fact that clones represented genotypes that increased in frequency during mouse and guinea pig passage, only the genetically diverse seed inoculum significantly surpassed all clones in causing mouse weight loss and lung histopathology. Interestingly, the clone with polymerase mutation D1124 (Genotype 2) was the only clone that resulted in significant weight loss for some of the mice and increased histopathology as compared with other clones ( Supplementary Fig. S5 , Table 2 ).