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.

Despite these studies the role that nutritional status plays on driving viral evolution within host under various nutritional statuses and the ability to infect a different host species have not been addressed. In this study, we address this gap in knowledge by serial passage of Sendai virus (SeV) (genus Respirovirus, Paramyxoviridae family) in mice under three different dietary conditions: normal diet (ND), selenium-deficient diet (SD), and high fat diet (FD). Following the last serial passage in mice, individual bronchial alveolar lavage (BAL) containing SeV from the three dietary conditions was used to infect guinea pigs under normal dietary conditions. Lung histopathology, viral titers, and cytokine profiles were used to characterize viral virulence within the hosts. Viral population dynamics were characterized using Illumina ultra-deep sequence analysis and computational modeling. SeV has a single-stranded, negative-sense RNA genome $15-16 kb in length which codes for six structural proteins: two glycoproteins hemagglutinin-neuraminidase (HN) and fusion protein (F), a matrix protein (M), and three nucleocapsid proteins, Nucleoprotein (N), Phosphoprotein (P), and Large polymerase protein (L). The P gene which codes for the P protein also codes for an additional set of up to seven different nested polyproteins (P, V, W, C', C, Y1, and Y2) and may be referred to as 'P/V/C' (Lamb and Parks 2007) . The HN glycoprotein plays critical role in mediating the virus entry into host cell and structural modeling was used to assess the impact mutations in this gene may have on protein function.