Mollentze, N. , Streicker, D. G. , Murcia, P. R. , Hampson, K. and Biek, R. (2020) Virulence mismatches in index hosts shape the outcomes of cross-species transmission. Proceedings of the National Academy of Sciences of the United States of America, 117(46), pp. 28859-28866. (doi: 10.1073/pnas.2006778117) (PMID:33122433) (PMCID:PMC7682402)
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Abstract
Whether a pathogen entering a new host species results in a single infection or in onward transmission, and potentially an outbreak, depends upon the progression of infection in the index case. Although index infections are rarely observable in nature, experimental inoculations of pathogens into novel host species provide a rich and largely unexploited data source for meta-analyses to identify the host and pathogen determinants of variability in infection outcomes. We analyzed the progressions of 514 experimental cross-species inoculations of rabies virus, a widespread zoonosis which in nature exhibits both dead-end infections and varying levels of sustained transmission in novel hosts. Inoculations originating from bats rather than carnivores, and from warmer- to cooler-bodied species caused infections with shorter incubation periods that were associated with diminished virus excretion. Inoculations between distantly related hosts tended to result in shorter clinical disease periods, which are also expected to impede onward transmission. All effects were modulated by infection dose. Taken together, these results suggest that as host species become more dissimilar, increased virulence might act as a limiting factor preventing onward transmission. These results can explain observed constraints on rabies virus host shifts, describe a previously unrecognized role of host body temperature, and provide a potential explanation for host shifts being less likely between genetically distant species. More generally, our study highlights meta-analyses of experimental infections as a tractable approach to quantify the complex interactions between virus, reservoir, and novel host that shape the outcome of cross-species transmission.
Item Type: | Articles |
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Additional Information: | N.M. was funded by a Lord Kelvin–Adam Smith studentship from the University of Glasgow. P.R.M. was funded by the Medical Research Council (MC_UU_12014/9). D.G.S. was supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and Royal Society (102507/Z/13/Z) and a Wellcome Senior Research Fellowship (217221/Z/19/Z). K.H. was supported by the Wellcome Trust (207569/Z/17/Z and 095787/Z/11/Z). |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Hampson, Professor Katie and Biek, Professor Roman and Mollentze, Dr Nardus and Streicker, Professor Daniel and Murcia, Professor Pablo |
Authors: | Mollentze, N., Streicker, D. G., Murcia, P. R., Hampson, K., and Biek, R. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
Publisher: | National Academy of Sciences |
ISSN: | 0027-8424 |
ISSN (Online): | 1091-6490 |
Published Online: | 29 October 2020 |
Copyright Holders: | Copyright © 2020 The Authors |
First Published: | First published in Proceedings of the National Academy of Sciences of the United States of America 117(46):28859-28866 |
Publisher Policy: | Reproduced under a Creative Commons License |
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