Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence

Cara E. Brook; Mike Boots; Kartik Chandran; Andrew P. Dobson; Christian Drosten; Andrea L. Graham; Bryan T. Grenfell; Marcel A. Müller; Melinda Ng; Lin-Fa Wang; Anieke van Leeuwen

We defined "induced immunity" as complete, modeling all cells as susceptible to viral 185 invasion at disease free equilibrium, with defenses induced subsequent to viral exposure through 186 the term . By contrast, we allowed the extent of constitutive immunity to vary across the 187 parameter range of > 0, defining a "constitutive" system as one containing any antiviral cells at 188 disease free equilibrium. In fitting this model to tissue culture data, we independently estimated 189 both and , as well as the cell-to-cell transmission rate, , for each cell-virus combination. Pathogens can invade a host tissue culture when 0 > 1. Rapid rates of constitutive antiviral 208 acquisition ( ) will drive 0 < 1: tissue cultures with highly constitutive antiviral immunity will 209 be therefore resistant to virus invasion from the outset. Since, by definition, induced immunity is 210 stimulated following initial virus invasion, the rate of induced antiviral acquisition ( ) is not 211 incorporated into the equation for 0 ; while induced immune processes can control virus after 212 initial invasion, they cannot prevent it from occurring to begin with. In cases of fully induced or 213 absent immunity ( = 0), the 0 equation thus reduces to a form typical of the classic SEIR 214 model: 215 12 know a constitutively antiviral cell-receptor incompatibility to be at play). Because constitutive 251 immune assumptions can prohibit pathogen invasion ( 0 < 1), model fits to this time series 252 under constitutive assumptions were handicapped by overestimations of , which prohibited 253 pathogen invasion. Only by incorporating an exceedingly rapid rate of induced antiviral 254 acquisition could the model guarantee that initial infection would be permitted and then rapidly 255 controlled. 256 257