Keynote speakersEEID 2021

We will explore the diversity of diseases featuring the usual parasite suspects across a wide range of host species.

Each afternoon we will have two keynote speakers on a given topic:

14th June: The crazy life of microbes

Many pathogens have evolved complex transmission strategies and/or life cycles. How do pathogens evolve these odd transmission strategies and what are the consequences for epidemiological and evolutionary dynamics? In this session we will explore the diversity of pathogen life histories and their (co)evolutionary origins.

15h00 CET Stéphane Blanc
Montpellier, France

How can multipartite viruses be functional and spread?

Multipartite viruses have two or more nucleic acid segments, each individually and thus separately encapsidated. As a consequence, their integral genome is not recapitulated in one but in a population of virus particles. The benefits and costs in such genetic systems and how they can actually be functional is a long-standing enigma. Using a multipartite nanovirus model we challenge some paradigms of virology and add new frames better comprehending these viral systems. We investigate their potential to rapidly adapt to changing environment through the modification of the frequency of their distinct genome segments. As a result, the segments with a low frequency have greater chances to get lost, further challenging the maintenance of the genome integrity. We then question whether and how the virus succeeds at introducing one copy of each of its genome segments in the target cells and hosts. The bold idea we pursue, and that is supported by recent results, is that the genome segments may not need to be together in individual cells, or to travel together in between hosts, for the system to function and propagate.

16h00 CET Kimberley Seed
Berkeley, US­

Fighting with phages:  how epidemic Vibrio cholerae defends against viral attack

Illness and death caused by infectious diarrheal disease agents, like Vibrio cholerae, are major threats to public health and significant barriers to socio-economic development worldwide. As the focus of several elegant studies documenting genomic changes in epidemic strains over the last century, V. cholerae has become a well-studied model for pathogen evolution. Despite this, the mechanisms and driving forces underlying historical and current changes are not yet understood. The arms race between viruses and their host organisms is a key driving force in the evolution of all cellular life. Indeed V. cholerae must defend against the ubiquitous threat of predatory phages in aquatic reservoirs and the intestinal tract during disease in humans. Our lab has shown that V. cholerae has evolved to use PLEs to defend against the predominant predatory phage ICP1. PLEs are parasitic mobile genetic elements that completely abolish ICP1 production while exploiting phage resources to further their own spread. Therefore, PLEs can be viewed both as defense systems for V. cholerae and as phage satellites that exploit ICP1 for their own mobilization. A significant hallmark of V. cholerae PLEs is that previously prevalent PLEs disappear globally when new variants emerge, indicating that each variant is selected by unknown factors over time. However, we do not understand why such changes occur and how new variants dominate over earlier prevalent variants. Ongoing work investigating how antagonism with ICP1 has driven the successive evolution of PLEs will be discussed.

15th June: Diversity of host resistance to pathogens

Several different host strategies can evolve to resist pathogens. Can we use this diversity to limit pathogen spread and evolution? In this session we will explore the dynamics of this diversity, its impact on pathogen epidemiology and potential counter-defenses in the pathogen population.

15h00 CET Jean-Benoit Morel
Montpellier, France

Eternal Rice: a case study of sustainable management of plant resistance

Important insights into ways to reach durability of plant disease resistance can be gained by studying existing sustainable systems, like the traditional rice agrosystem of the Yuan Yang Terraces (YYT) in China. In YYT, more than 190 traditional rice varieties have been grown for centuries without noticeable erosion of resistance to the blast fungus Magnaporthe oryzae. The main objective of the multi-disciplinary project “Riz Eternel” was to test the hypothesis that the crop diversity and the spatio-temporal arrangement of varieties prevents the development of large epidemics of M. oryzae. Genome analysis of hundreds of plants showed that the traditional rice varieties are populations, highly diversified, with resistance genes under diversifying selection. Socio-economic surveys allowed the identification of social rules underlying seed exchange within villages, producing additional levels of spatial and temporal diversity. As a consequence, there is no genetic co-structure between plants and M. oryzae populations, suggesting that M. oryzae is maladapted in YYT.
Combining socio-economic approaches and molecular genetics, we also present recent evidence that shrinking of cultivated rice diversity in YYT destabilizes the co-evolutionary equilibrium and favors epidemics.

16h00 CET Anne Chevallereau
Paris, France

The Benefits of Diversity-generating Bacterial ‘CRISPR-Cas’ Immune Systems
are mitigated by Bacteriophage-encoded ‘anti-CRISPR’

Bacteria are under constant threat from viruses (known as phages) which led to the evolution of a large repertoire of resistance mechanisms, amongst which ‘CRISPR-Cas’ is one of the most widespread. This immune system captures elements from the invader’s genome (spacers) into CRISPR loci to provide sequence-specific immunity against (re)infecting phages. The modalities of spacer acquisition allow the generation of high levels of spacer-diversity within bacterial populations, which is key to limit phage epidemics and evolution of escape mutations. However, this CRISPR-mediated selection has likely driven the evolution of ‘anti-CRISPR’ (Acr) mechanisms in phage populations. These Acr-phages have remarkable ecological dynamics: a first ‘sacrificial’ phage takes CRISPR defences down but fails to replicate, which allows a second phage to successfully multiply on this immunosuppressed host. In addition to their ecological effects, Acr inhibit spacer acquisition in the host and hence, the evolution phage-resistance. The fitness benefits provided by CRISPR-Cas are therefore annulled when predatory phages encode Acr. However, CRISPR-Cas may become maladaptive (e.g. in the presence of parasitic and/or mutualistic phages), in which cases Acr not only benefit the phage but also the host. In summary, I will discuss the diversity-generating benefits of CRISPR-Cas systems and highlight how the evolution of anti-CRISPR allowed phages to adapt.

16th June: Using genomics and immunity to infer pathogen dynamics

Genomics and serological studies provide new data on pathogens. Can we use this data to learn about the ecology and the evolution of infectious diseases? In this session we will explore how genomics and immunity profiles can help understand past epidemics and prevent future ones.

15h00 CET Katrina Lythgoe
Oxford, UK

Levels of selection in chronic and acute viruses: From HIV to SARS-CoV-2

Viruses replicate and evolve within the hosts that they infect, but sooner or later they need to transmit if they are going to survive in the long term. This creates an evolutionary trade-off, because what makes a virus fit within a given individual does not necessarily make it good at transmitting. We might expect this tension to be strongest for chronic viral infections, like HIV, which can undergo years of rapid within-host evolution between transmission events. But for acute viruses, like SARS-CoV-2, these tensions are expected to be weak as the virus rapidly jumps from individual to individual, with little opportunity for within-host selection. This is supported out by ours’ and others’ findings that when viral loads are high and transmission is most likely, SARS-CoV-2 has little genetic diversity and a narrow transmission bottleneck. How then does the appearance and success of new variants of concern, which apparently emerged within chronically infected individuals, fit into this framework? I argue that by changing the properties of the host population, for example as a consequence of host shifts or mass vaccination, we are fundamentally changing the nature of the trade-off between selection at the within- and between-host levels.

16h00 CET Henrik Salje
Cambridge, UK

Using pathogen genomes to identify the role of human behaviours in disease spread

Behaviour is central to infectious disease spread. How we move around and interact with each other and the local environment drive transmission patterns within a population. Understanding the role of behaviour in the spread of human pathogens is, however, complicated. Disease surveillance systems typically only observe a small proportion of all infections, which means we don’t know how related any two cases are. They also rarely capture the behaviours that resulted in infection, including age-specific contact patterns and mobility patterns of both the infected individual and the people they go on to infect. Genetic data can help reconstruct how pathogens have moved within and between locations. However, phylogenetic approaches have been complicated by uneven availability of sequences in time and space. Some places will typically provide the bulk of sequences with most locations providing no sequences at all.  In this talk I will present analytical approaches that can identify the role of behaviour using human mobility data and age contact matrices. I will apply these methods to dengue virus and SARS-CoV-2 and demonstrate their ability to accurately identify how a virus is moving at each transmission step, even when only a small subset of locations provide sequences. 

17th June: Disease control: epidemiological, ecological and evolutionary consequences

Different control strategies (vaccination, drugs…) can be used to control infectious diseases. What are the epidemiological and evolutionary consequences of these interventions? In this session we will discuss how to optimise control strategies.

15h00 CET Jessica Metcalf
Princeton, US

Questioning control: evaluating options, estimating impacts, and considering the longer term

The options for SARS-CoV-2 control were initially limited. As a directly transmitted infection, the only tools available to reduce cases for the first year of the pandemic were behavioral. In 2021, availability of vaccines brightened the situation considerably, but vaccine doses remain limited in many settings. I will discuss efforts to evaluate options for control (from aspects of test-trace-isolate, to vaccine deployment in Madagascar), to estimate the impact of different interventions (from design of trials to use of novel data such as social-media based survey instruments and mobile phone call data records), and for considering the longer term given core uncertainties around immunity and the landscape of selection on the pandemic virus. 


16h00 CET Scott Nuismer
Idaho, US

Transmissible vaccines : epidemiological and evolutionary perspectives 

Spillover from wild animal populations fuels the origin and recurrence of many emerging infectious diseases. This creates opportunities to decrease the threat of emergence by reducing or eliminating pathogens within their animal reservoirs. Transmissible vaccines are a powerful new technology that may allow these opportunities to be realized at broad scale. Here I provide a brief history of transmissible vaccines and an overview of the methods used to create them. I then present the results of mathematical models grounded in the biology of transmissible vaccines currently being developed for emerging infectious diseases of humans. The results of these models quantify the impact of transmissible vaccines on pathogen populations and identify key design challenges that must be overcome for transmissible vaccines to be both evolutionarily stable and epidemiologically effective.