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.

Perhaps the most surprising result from this study is the lack of histopathologic lesions in any of the three guinea pigs that were infected with FD.P10 inoculum. Although limited sequencing data were available from these animals, no changes were observed that differentiated FD.GP samples or the FD.P10 from the corresponding samples from the ND and SD groups. However, the combination of amino acids (residues 454, 461, 525) at these three sites is unique for FD.GP1 (the only FD.GP with sequence data for the HN gene). FD.GP1 had HN genotype AKQ (residues 454, 461, 525, respectively), as compared with genotypes AEK and VKQ for the ND.GP and SD.GP samples. Thus, it is possible that it is the unique combination of AKQ that attenuates the virus in guinea pigs. Alternatively other parameters such as temporal aspects of host response may have affected histopathology scores. For example, obesity may result in a delayed pro-inflammatory response to influenza virus infection (Smith et al. 2007) , if this response is also delayed in Sendai infected animals, this may have resulted in decreased histopathology scores in the FD group (Fig. 2C) .