Superinfection and the evolution of an initial asymptomatic stage

Author:

Saad-Roy Chadi M.1ORCID,Grenfell Bryan T.234,Levin Simon A.2,Pellis Lorenzo56ORCID,Stage Helena B.5ORCID,van den Driessche P.7,Wingreen Ned S.18

Affiliation:

1. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA

2. Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA

3. Princeton School of Public and International Affairs, Princeton University, Princeton, NJ, USA

4. Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, MD, USA

5. Department of Mathematics, University of Manchester, Manchester, UK

6. The Alan Turing Institute, London, UK

7. Department of Mathematics and Statistics, University of Victoria, Victoria, British Columbia, Canada

8. Department of Molecular Biology, Princeton University, Princeton, NJ, USA

Abstract

Pathogens have evolved a variety of life-history strategies. An important strategy consists of successful transmission by an infected host before the appearance of symptoms, that is, while the host is still partially or fully asymptomatic. During this initial stage of infection, it is possible for another pathogen to superinfect an already infected host and replace the previously infecting pathogen. Here, we study the effect of superinfection during the first stage of an infection on the evolutionary dynamics of the degree to which the host is asymptomatic (host latency) in that same stage. We find that superinfection can lead to major differences in evolutionary behaviour. Most strikingly, the duration of immunity following infection can significantly influence pathogen evolutionary dynamics, whereas without superinfection the outcomes are independent of host immunity. For example, changes in host immunity can drive evolutionary transitions from a fully symptomatic to a fully asymptomatic first infection stage. Additionally, if superinfection relative to susceptible infection is strong enough, evolution can lead to a unique strategy of latency that corresponds to a local fitness minimum, and is therefore invasible by nearby mutants. Thus, this strategy is a branching point, and can lead to coexistence of pathogens with different latencies. Furthermore, in this new framework with superinfection, we also find that there can exist two interior singular strategies. Overall, new evolutionary outcomes can cascade from superinfection.

Funder

Natural Sciences and Engineering Research Council of Canada

Wellcome Trust

Centers for Disease Control and Prevention

National Institutes of Health

Royal Society

James S. McDonnell Foundation

National Science Foundation

Publisher

The Royal Society

Subject

Multidisciplinary

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