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 diversity of viral genomes present in an intra-host population provides an enormous pool of genetic and phenotypic variants and this increases the likelihood of emergence of a variant with a high virulence phenotype. Host nutritional status may influence the generation of variant viruses by altering the selective pressure induced by the host immune response (Domingo and Holland 1997) or by acting on the fidelity of the viral polymerases Beck, Handy, and Levander 2004; Yoshitake et al. 2004; Zaki, Akuta, and Akaike 2005) . In this study, we tested the hypothesis that undernutrition (selenium deficiency) and/or overnutrition (high FD) leads to decreased immune response, increased mutant spectrum variability, and evolution of increased virulence during in vivo passage. Deep Illumina sequencing was used to define the viral mutant spectra during serial passage and a host-jump from mice to guinea pigs. Virus phenotype (lung pathology, viral titer) and host response (weight loss, cytokine expression) were characterized.