Dynamics of viral index infections in novel hosts

Nardus Mollentze; Daniel G. Streicker; Pablo R. Murcia; Katie Hampson; Roman Biek

Clinical period 151 7 host species appeared to affect the duration of clinical periods. Cross-species inoculations between 156 phylogenetically more distant species were associated with an increased sensitivity to high viral 157 doses, resulting in shorter clinical periods ( Figure 2E ). However, the overall effect size estimate 158 for this interaction included zero (Figure 2A ). Bat-associated viruses appeared to have shorter 159 clinical periods, and -as also observed for incubation periods -this effect depended on dose, but 160 here it was poorly estimated, with the HPD again including zero ( Figure 2A ). All other fixed effects 161 were small, and none could be clearly separated from zero, but combined the fixed effects 162 explained 40.3% of the variation in clinical period duration (HPD: 12.9 -64.0%). accounted for by the inoculated species phylogeny ( Figure 3B ). The remaining residual correlation 176 is explained by differences in dose ( Figure 3C ), with higher doses leading to decreased salivary 177 gland titres ( Figure 3D ). The inoculation of species with a lower body temperature than the 178 reservoir also tended to reduce the virus titre in the salivary glands, although the size of this effect 179 could not be estimated precisely enough to make it distinct from zero (positive body temperature 180 differences, Figure 3D & E). A clearer effect was observed for the interaction of reservoir status 181 and dose: at low doses, known rabies reservoir species produced higher virus titres in the salivary 182 glands than non-reservoirs ( Figure 3G ). At very high doses, however, we detected no difference in 183 salivary gland titres, possibly because animals succumb too fast for any differences to develop. 184 . CC-BY 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.09.033928 doi: bioRxiv preprint log(1 + Salivary gland titre) The progression of viral infections within the index host following cross-species transmission is a 236 crucial determinant of onward transmission, but is generally unobservable in nature. By analysing 237 a unique dataset of experimental cross-species infections, we demonstrate that phylogenetic 238 distance and specific physiological differences between the host species involved alter the 239 progression of infections in ways that are expected to influence whether transmission in the novel 240 host is sustained. 241