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.

The nutritional status of the host and its relation to infection and immunity has been well documented (Beck 1996; Beisel 1996; Chandra 1997; Keusch 2003; Beck, Handy, and Levander 2004; Schaible and Kaufmann 2007; Alice, Tang, and Semba 2013) . These studies have primarily focused on malnutrition of the host; however, more recent studies have begun to look at the role obesity plays in infection and immunity (Nieman et al. 1999; Ritz and Gardner 2006; Kanneganti and Dixit 2012) . In this study, we focused on the role malnutrition (in the form of selenium deficiency) and diet induced obesity had in mice infected with SeV to understand the effects these two dietary conditions have on the viral mutant spectra and infection dynamics. Dietinduced obesity has been demonstrated to alter cytokine profiles in mice (Mito et al. 2000) . Consistent with those studies, our studies found altered cytokine profiles in uninfected FD mice compared with SD and ND mice ( Supplementary Fig. S2 ). In SeV-infected mice there were no differences found in cytokine expression profiles associated with in vivo passage within The average was calculated using the maximum weight loss over the course of the infection for each mouse infected c Mixture of clones consisted of clones representing genotypes 1, 2, 3, 5, 6, 7, 8, and 10. The remaining genotypes did not replicate well enough to allow adequate titer. dietary groups; however, further analysis of cytokine profiles between the dietary groups found SD mice infected with SeV had a suppressed immune response compared with ND and FD mice infected with SeV ( Supplementary Fig. S2) . Similarly, mice infected with influenza virus receiving a selenium deficient diet have been shown to have suppressed cytokine profiles compared with mice receiving a ND (Beck et al. 2001 ).