Virulence mismatches in index hosts shape the outcomes of cross-species transmission

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
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:Biek, Professor Roman and Streicker, Dr Daniel and Mollentze, Dr Nardus and Hampson, Professor Katie 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 > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630Quinquennial Core FundsMassimo PalmariniMedical Research Council (MRC)MC_UU_12014/9III-MRC-GU CVR Support Services
169793Managing viral emergence at the interface of bats and livestockDaniel StreickerWellcome Trust (WELLCOTR)102507/Z/13/ZRInstitute of Biodiversity, Animal Health and Comparative Medicine
307106Epidemiology meets biotechnology: preventing viral emergence from batsDaniel StreickerWellcome Trust (WELLCOTR)217221/Z/19/ZInstitute of Biodiversity, Animal Health and Comparative Medicine
301620The Science of Rabies EliminationKatie HampsonWellcome Trust (WELLCOTR)207569/Z/17/ZInstitute of Biodiversity, Animal Health and Comparative Medicine