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.

Data from Fujii et al. (2002) using a pathogenic field isolate of SeV, the Hamamatsu strain, showed that two regions of the Sendai leader sequence, nts 20 and 24, mutated during serial passage in embryonated eggs (U20A and U24A), with an A at both sites resulting in an attenuated phenotype in mice (Fujii et al. 2002) . Our data obtained from Sanger sequencing of clone isolates of the lab-adapted strain 52 showed a trend of G to A mutation for nt site 20 as egg-passaged seed virus was passaged serially in mice. In fact, there was an increase in the percentage of clones from P10 having an A as compared with P1 (17% of the clones from P1 had an A, whereas by P10 an A was detected in 48% of clones). Analysis of about eight clones per sample revealed that most samples (6/11) had a mixture of nts at nt 20. However, all of the 85 clones that were sequenced in this study had an A at nt 24. Thus, our data confirm the variability of nt site 20 as described by Fujii et al. and illustrate how consensus sequence data alone may hide the complexities of the viral population diversity.