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 precise mechanism(s) by which in vivo passage leads to increased virulence are not clear and may differ between viral families, genera, and even species. In vivo passage outcome is shaped by numerous factors including viral strain, genotypic diversity, size of the inoculum, route of exposure, and by host factors such as onset and strength of immune response (Kuss, Etheredge, and Pfeiffer, 2008; Gutié rrez, Michalakis, and Blanc 2012; Morelli, et al. 2013) . Decreased immunocompetence may allow infecting viruses to cause prolonged infections which may increase the size and depth of genetic diversity present in the intra-host population of RNA viruses (Domingo 1997) . Immunocompetence of a host is determined by many factors such as age, pregnancy, and nutrient intake (Levander 1997; Beck, Levander, and Handy 2003; Beck 2007) . Recent studies by Beck and others suggest that both malnutrition and obesity adversely affect the ability of a host to mount a robust innate and adaptive immune response to viral infections (Beck, Handy, and Levander 2004; Zaki, Akuta, and Akaike 2005; Karlsson and Beck 2009) . For example, obese mice infected with influenza virus had a significantly higher mortality and increased lung pathology as compared with lean mice (Smith et al. 2007) . Similarly, infection of selenium deficient mice with an avirulent strain of Coxsackievirus B3 resulted in evolution of the virus into a virulent form that caused cardiac inflammation in both selenium deficient mice and normal control mice (Beck et al. 1995; Beck, Williams-Toone, and Levander 2003) .