Natural selection and dynamical coexistence of defective and complementing virus segments.

Defective interfering (DI) particles are known to coexist with wildtype viruses under high multiplicity of infection. The complementing segments of coviruses (multiparticle, segmented viruses) coexist under similar conditions. In all cases, within-cell reproductive advantage to one of the segments is rather common. This fact, and the observation that DI particles are parasites, whereas covirus segments are mutualists, call for a non-trivial model of stable dynamical coexistence. The methodical novelty is the application of the structured deme model to virus dynamics. It assumes that biochemical ("ecological") interactions occur among segments within a coinfection group, established through random infection of the cells, and there is complete mixing of the various types emerging from all the coinfection groups (cells) in the virus pool between two infections. Through the application of the model, analytic results on the coexistence of virus segments are obtained for the following cases: virus-DI particle, virus-DI particle-resistant virus, covirus pair, virus-covirus.     

Trade-offs between and within scales: environmental persistence and within-host fitness of avian influenza viruses

Trade-offs between different components of a pathogen''s replication and transmission cycle are thought to be common. A number of studies have identified trade-offs that emerge across scales, reflecting the tension between strategies that optimize within-host proliferation and large-scale population spread. Most of these studies are theoretical in nature, with direct experimental tests of such cross-scale trade-offs still rare. Here, we report an analysis of avian influenza A viruses across scales, focusing on the phenotype of temperature-dependent viral persistence. Taking advantage of a unique dataset that reports both environmental virus decay rates and strain-specific viral kinetics from duck challenge experiments, we show that the temperature-dependent environmental decay rate of a strain does not impact within-host virus load. Hence, for this phenotype, the scales of within-host infection dynamics and between-host environmental persistence do not seem to interact: viral fitness may be optimized on each scale without cross-scale trade-offs. Instead, we confirm the existence of a temperature-dependent persistence trade-off on a single scale, with some strains favouring environmental persistence in water at low temperatures while others reduce sensitivity to increasing temperatures. We show that this temperature-dependent trade-off is a robust phenomenon and does not depend on the details of data analysis. Our findings suggest that viruses might employ different environmental persistence strategies, which facilitates the coexistence of diverse strains in ecological niches. We conclude that a better understanding of the transmission and evolutionary dynamics of influenza A viruses probably requires empirical information regarding both within-host dynamics and environmental traits, integrated within a combined ecological and within-host framework.     

Alternating Host Cell Tropism Shapes the Persistence,Evolution and Coexistence of Epstein–Barr Virus Infections in Human

Epstein–Barr virus (EBV) infects and can persist in a majority of people worldwide. Within an infected host, EBV targets two major cell types, B cells and epithelial cells, and viruses emerging from one cell type preferentially infect the other. We use mathematical models to understand why EBV infects epithelial cells when B cells serve as a stable refuge for the virus and how switching between infecting each cell type affects virus persistence and shedding. We propose a mathematical model to describe the regulation of EBV infection within a host. This model is used to study the effects of parameter values on optimal viral strategies for transmission, persistence, and intrahost competition. Most often, the optimal strategy to maximize transmission is for viruses to infect epithelial cells, but the optimal strategy for maximizing intrahost competition is for viruses to mainly infect B cells. Applying the results of the within-host model, we derive a model of EBV dynamics in a homogeneous population of hosts that includes superinfection. We use this model to study the conditions necessary for invasion and coexistence of various viral strategies at the population level. When the importance of intrahost competition is weak, we show that coexistence of different strategies is possible.     

From antagonistic larvae to mutualistic adults: coevolution of diet niches within life cycles

Population structures largely affect higher levels of organization (community structure, ecosystem functioning), especially when involving ontogenetic changes in habitat or diet. Along life cycles, partners and interaction type may change: for instance Lepidopterans are herbivores as larvae and pollinators as adults. To understand variations in diet niche from larvae to adults, we model a community of two plant species and one stage‐structured insect species consuming plants as juvenile and pollinating them as adult. We model the coevolution of juvenile and adult diet specialization using adaptive dynamics to investigate when one should expect niche partitioning or niche overlap among life stages. We consider ecological and evolutionary implications for the coexistence of species. As predicted based on indirect effects among stages, we find that juvenile diet evolution increases niche overlap and favours the coexistence of plants, while the evolution of the adult diet decreases niche overlap and reduces plant coexistence, because of positive feedbacks emerging from the mutualistic interaction.     

Control in mutualisms: Combined implications of partner choice and bargaining roles

When two species form a mutualistic association, the degree of control that each has over the interaction may be pivotal in determining the relative benefit each obtains. We incorporate the capacity for partner choice into a model of mutualism based on the exchange of goods and/or services, where one guild of mutualists plays the role of proposer (proposing a price at which the goods and/or services will be exchanged) and the other plays the role of responder (accepting or rejecting the deal). We show how the payoff structure in this scenario and other closely related ones correspond to the ultimatum and demand games of economics. In the model, there are both costs and benefits to a guild whose players have control over interactions. Control over interactions in the sense of being able to exercise partner choice can benefit a guild by selecting for mutualism in its partners, but is most effective in selecting against moderately exploitative partners, and so can give highly exploitative partners an advantage. This can generate dynamics similar to taxon cycles or those seen in models with competition-colonization tradeoffs, wherein increasingly more mutualistic partners (acting as superior competitors) are selected for up to a tipping point, at which highly exploitative strategies (akin to superior colonizers) gain an advantage. Control over interactions in the sense of being able to appropriate ‘surplus’ payoffs in each interaction, which is selected for within-guild and is equivalent to playing the role of responders, selects against high demands (and so for mutualism) in the guild with control. Combining the two mechanisms, a high degree of mutualism in both guilds and coexistence of more mutualistic and more exploitative strategies within each are both consistent with control over the interaction being highly skewed toward one side that does what is in its own short-term interests.     

Potential impacts of multiple partners on mycorrhizal community dynamics

The significance of arbuscular mycorrhizal (AM) fungi in terrestrial ecosystems is widely acknowledged, but the causes and consequences of diversity in these fungi are not well understood. A recent frequency-dependent model suggests that dynamics within mycorrhizal mutualisms could promote the coexistence of at least two competing plant species and two competing fungal species within a community. Models are developed here in which simultaneous association with multiple partners may result in elevated or depressed fitness relative to association with either partner alone. This increases the range of conditions under which negative feedback occurs and coexistence of all four species is possible. Differences between plants in the relative proportions of fungi at which maximum fitness occurs may facilitate coexistence, as may differences between fungi in their abilities to establish interplant connections. These models suggest additional mechanisms by which mutualistic interactions could promote local diversity of plants and AM fungi.     

Choindroitinase ABC I-Mediated Enhancement of Oncolytic Virus Spread and Anti Tumor Efficacy: A Mathematical Model

Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV). We show that the model''s predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment.     

Persistence of mutualisms with bidirectional interactions in a two-species system

In Lotka–Volterra equations (LVEs) of mutualisms, population densities of mutualists will increase infinitely if the mutualisms between them are strong, which is called the divergence problem. In order to avoid the problem, a mutualism system of two species is analyzed in this work. The model is derived from reactions on lattice and has a form similar to that of LVEs. Population densities of species will not increase infinitely because of spatial limitation on the lattice. Stability analysis of the model demonstrates basic mechanisms by which the mutualisms lead to coexistence/extinction of the species. When in coexistence, intermediate mutualistic effect is shown to lead to the maximal density in certain parameter ranges, while a strong or weak mutualistic effect is not so good. Furthermore, the stability analysis exhibits that extremely strong/weak mutualisms will result in extinction of one/both species.     

Stability of a diamond-shaped module with multiple interaction types

Indirect interactions among species emerge from the complexity of ecological networks and can strongly affect the response of communities to disturbances. To determine these indirect interactions and understand better community dynamics, ecologists focused on the interactions within small sets of species or modules. Thanks to their analytical tractability, modules bring insights on the mechanisms occurring in complex interaction networks. So far, most studies have considered modules with a single type of interaction although numerous species are involved in mutualistic and antagonistic interactions simultaneously. In this study, we analyse the dynamics of a diamond-shaped module with multiple interaction types: two resource species sharing a mutualist and a consumer. We describe the different types of indirect interaction occurring between the resource species and the conditions for a stable coexistence of all species. We show that the nature of indirect interactions between resource species (i.e. apparent facilitation, competition or antagonism), as well as stable coexistence, depend on the species generalism and asymmetry of interactions, or in other words, on the distribution of interaction strengths among species. We further unveil that a balance between mutualistic and antagonistic interactions at the level of resource species favours stable coexistence, and that species are more likely to coexist stably if there is apparent facilitation between the two resource species rather than apparent competition. Our results echo existing knowledge on the trophic diamond-shaped module, and confirm that our understanding of communities combining different interaction types can gain from module analyses.     

Standing genetic variation in host preference for mutualist microbial symbionts

Many models of mutualisms show that mutualisms are unstable if hosts lack mechanisms enabling preferential associations with mutualistic symbiotic partners over exploitative partners. Despite the theoretical importance of mutualism-stabilizing mechanisms, we have little empirical evidence to infer their evolutionary dynamics in response to exploitation by non-beneficial partners. Using a model mutualism—the interaction between legumes and nitrogen-fixing soil symbionts—we tested for quantitative genetic variation in plant responses to mutualistic and exploitative symbiotic rhizobia in controlled greenhouse conditions. We found significant broad-sense heritability in a legume host''s preferential association with mutualistic over exploitative symbionts and selection to reduce frequency of associations with exploitative partners. We failed to detect evidence that selection will favour the loss of mutualism-stabilizing mechanisms in the absence of exploitation, as we found no evidence for a fitness cost to the host trait or indirect selection on genetically correlated traits. Our results show that genetic variation in the ability to preferentially reduce associations with an exploitative partner exists within mutualisms and is under selection, indicating that micro-evolutionary responses in mutualism-stabilizing traits in the face of rapidly evolving mutualistic and exploitative symbiotic bacteria can occur in natural host populations.     

Movement can mediate temporal mismatches between resource availability and biological events in host–pathogen interactions

Global change is shifting the timing of biological events, leading to temporal mismatches between biological events and resource availability. These temporal mismatches can threaten species’ populations. Importantly, temporal mismatches not only exert strong pressures on the population dynamics of the focal species, but can also lead to substantial changes in pairwise species interactions such as host–pathogen systems. We adapted an established individual‐based model of host–pathogen dynamics. The model describes a viral agent in a social host, while accounting for the host''s explicit movement decisions. We aimed to investigate how temporal mismatches between seasonal resource availability and host life‐history events affect host–pathogen coexistence, that is, disease persistence. Seasonal resource fluctuations only increased coexistence probability when in synchrony with the hosts’ biological events. However, a temporal mismatch reduced host–pathogen coexistence, but only marginally. In tandem with an increasing temporal mismatch, our model showed a shift in the spatial distribution of infected hosts. It shifted from an even distribution under synchronous conditions toward the formation of disease hotspots, when host life history and resource availability mismatched completely. The spatial restriction of infected hosts to small hotspots in the landscape initially suggested a lower coexistence probability due to the critical loss of susceptible host individuals within those hotspots. However, the surrounding landscape facilitated demographic rescue through habitat‐dependent movement. Our work demonstrates that the negative effects of temporal mismatches between host resource availability and host life history on host–pathogen coexistence can be reduced through the formation of temporary disease hotspots and host movement decisions, with implications for disease management under disturbances and global change.     

Mutualistic relationships between phytoplankton and bacteria caused by carbon excretion from phytoplankton

For the competition system of phytoplankton and bacteria through inorganic phosphorus, our mathematical model showed that mutualistic relationships between them could occur due to production and consumption of extracellular organic carbon by phytoplankton and bacteria. In our model, phytoplankton are limited in their growth by light and phosphorus, and bacteria are limited in their growth by phosphorus and carbon released from phytoplankton. We adopted permanence as a criterion of the coexistence in mathematical analysis, and led necessary conditions of permanence in the model. Under these coexistence conditions, we estimated the strength of total effects of interactions between phytoplankton and bacteria at the steady state by press perturbation method. The results of this estimation indicated the mutualistic interactions between phytoplankton and bacteria. This suggests that mutualistic situation could occur due to the introduction of carbon flow from phytoplankton to bacteria, even if phytoplankton and bacteria compete with each other through common resource, inorganic phosphorus.     

Bats and zoonotic viruses: can we confidently link bats with emerging deadly viruses?

An increasingly asked question is ''can we confidently link bats with emerging viruses?''. No, or not yet, is the qualified answer based on the evidence available. Although more than 200 viruses - some of them deadly zoonotic viruses - have been isolated from or otherwise detected in bats, the supposed connections between bats, bat viruses and human diseases have been raised more on speculation than on evidence supporting their direct or indirect roles in the epidemiology of diseases (except for rabies). However, we are convinced that the evidence points in that direction and that at some point it will be proved that bats are competent hosts for at least a few zoonotic viruses. In this review, we cover aspects of bat biology, ecology and evolution that might be relevant in medical investigations and we provide a historical synthesis of some disease outbreaks causally linked to bats. We provide evolutionary-based hypotheses to tentatively explain the viral transmission route through mammalian intermediate hosts and to explain the geographic concentration of most outbreaks, but both are no more than speculations that still require formal assessment.     

Intraspecific competition in models for vegetation patterns: Decrease in resilience to aridity and facilitation of species coexistence

Patterned vegetation is a characteristic feature of many dryland ecosystems. While plant densities on the ecosystem-wide scale are typically low, a spatial self-organisation principle leads to the occurrence of alternating patches of high biomass and patches of bare soil. Nevertheless, intraspecific competition dynamics other than competition for water over long spatial scales are commonly ignored in mathematical models for vegetation patterns. In this paper, I address the impact of local intraspecific competition on a modelling framework for banded vegetation patterns. Firstly, I show that in the context of a single-species model, neglecting local intraspecific competition leads to an overestimation of a patterned ecosystem’s resilience to increases in aridity. Secondly, in the context of a multispecies model, I argue that local intraspecific competition is a key element in the successful capture of species coexistence in model solutions representing a vegetation pattern. For both models, a detailed bifurcation analysis is presented to analyse the onset, existence and stability of patterns. Besides the strengths of local intraspecific competition, also the difference between two species has a significant impact on the bifurcation structure, providing crucial insights into the complex ecosystem dynamics. Predictions on future ecosystem dynamics presented in this paper, especially on pattern onset and pattern stability, can aid the development of conservation programs.     

CRISPR-Induced Distributed Immunity in Microbial Populations

In bacteria and archaea, viruses are the primary infectious agents, acting as virulent, often deadly pathogens. A form of adaptive immune defense known as CRISPR-Cas enables microbial cells to acquire immunity to viral pathogens by recognizing specific sequences encoded in viral genomes. The unique biology of this system results in evolutionary dynamics of host and viral diversity that cannot be fully explained by the traditional models used to describe microbe-virus coevolutionary dynamics. Here, we show how the CRISPR-mediated adaptive immune response of hosts to invading viruses facilitates the emergence of an evolutionary mode we call distributed immunity - the coexistence of multiple, equally-fit immune alleles among individuals in a microbial population. We use an eco-evolutionary modeling framework to quantify distributed immunity and demonstrate how it emerges and fluctuates in multi-strain communities of hosts and viruses as a consequence of CRISPR-induced coevolution under conditions of low viral mutation and high relative numbers of viral protospacers. We demonstrate that distributed immunity promotes sustained diversity and stability in host communities and decreased viral population density that can lead to viral extinction. We analyze sequence diversity of experimentally coevolving populations of Streptococcus thermophilus and their viruses where CRISPR-Cas is active, and find the rapid emergence of distributed immunity in the host population, demonstrating the importance of this emergent phenomenon in evolving microbial communities.     

Viruses,cancer and non-self recognition

Virus–host interactions form an essential part of every aspect of life, and this review is aimed at looking at the balance between the host and persistent viruses with a focus on the immune system. The virus–host interaction is like a cat-and-mouse game and viruses have developed ingenious mechanisms to manipulate cellular pathways, most notably the major histocompatibility (MHC) class I pathway, to reside within infected cell while evading detection and destruction by the immune system. However, some of the signals sensing and responding to viral infection are derived from viruses and the fact that certain viruses can prevent the infection of others, highlights a more complex coexistence between the host and the viral microbiota. Viral immune evasion strategies also illustrate that processes whereby cells detect and present non-self genetic material to the immune system are interlinked with other cellular pathways. Immune evasion is a target also for cancer cells and a more detailed look at the interfaces between viral factors and components of the MHC class I peptide-loading complex indicates that these interfaces are also targets for cancer mutations. In terms of the immune checkpoint, however, viral and cancer strategies appear different.     

T4-like myovirus community shaped by dispersal and deterministic processes in the South China Sea

As the most abundant and genetically diverse biological entities, viruses significantly influence ecological, biogeographical and evolutionary processes in the ocean. However, the biogeography of marine viruses and the drivers shaping viral community are unclear. Here, the biogeographic patterns of T4-like viruses and the relative impacts of deterministic (environmental selection) and dispersal (spatial distance) processes were investigated in the northern South China Sea. The dominant viral operational taxonomic units were affiliated with previously defined Marine, Estuary, Lake and Paddy Groups. A clear viral biogeographic pattern was observed along the environmental gradient from the estuary to open sea. Marine Groups I and IV had a wide geographical distribution, whereas Marine Groups II, III and V were abundant in lower-salinity continental or eutrophic environments. A significant distance-decay pattern was noted for the T4-like viral community, especially for those infecting cyanobacteria. Both deterministic and dispersal processes influenced viral community assembly, although environmental selection (e.g. temperature, salinity, bacterial abundance and community, etc.) had a greater impact than spatial distance. Network analysis confirmed the strong association between viral and bacterial community composition, and suggested a diverse ecological relationship (e.g. lysis, co-infection or mutualistic) between and within viruses and their potential bacterial hosts.     

Viral sex, levels of selection, and the origin of life.

Several issues in Chao's related paper J. theor. Biol. (1991, 153, 229-246) are revisited. It is argued that mixes of segments from different viral coinfection groups cannot be regarded as sex, unless one is willing to accept that these groups are replicators and individuals. But, because selection in coinfection groups is dynamically analogous to that in trait groups in structured demes, one should also regard these latter groups as replicators. This approach is unacceptable since the groups in question have irregular ploidies, an unfixed number of parents, and no rules analogous to those of meiosis. It is emphasized, however, that the effective presence of neighbour-modulated fitness can ensure dynamical coexistence of covirus segments, even if the equal net reproduction rate within groups is not warranted. It seems that during the origin of coviruses from complete viruses, a higher-level evolutionary unit has become disintegrated, whereas during the origin of life a higher-level unit, the protocell, has emerged from lower-level ones, i.e. unlinked, replicating genes. These two gene-level systems are not homologous, but analogous. Although it is true that the resistance to parasites and the need to avoid a mutational collapse of the genome are likely to have called for some compartmentation in precellular stages of evolution, no clear demonstration, that the proposed mechanisms (the compartmentalized hypercycle and the stochastic corrector model) do in fact solve the error threshold problem, exists. Neither has a plausible mode of protocellular sex been suggested.     

Adaptation in a hybrid world with multiple interaction types: a new mechanism for species coexistence

In ecological communities, numerous species coexist and affect each others’ population levels via various types of interspecific interactions. Previous ecological theory explaining multispecies coexistence tended to focus on a single interaction type, such as antagonism, competition, or mutualism, and its consequences on population dynamics. Hence, it remains unclear what, if any, contribution multiple coexisting interaction types have on the multispecies coexistence. Here, we show that the coexistence of multiple interaction types can be essential for multispecies coexistence. We present a simple model in which the exploiter and mutualist adaptively switch between two competing resource species. An adaptive mutualist, which favors the more abundant species, provides a mechanism of majority-advantage and, thus, potentially inhibits the coexistence of resource species. In the absence of an exploiter, an adaptive mutualist leads to competitive exclusion at the resource species level. However, the coexistence of an adaptive exploiter and a mutualist allows the coexistence of all species in the community, because the mutualist-mediated “winner” tends to be suppressed by the adaptive exploiter. The mutualist indirectly increases the abundance of the exploiter through mutualistic interactions, thereby indirectly supporting this coexistence mechanism. In fact, coexistence may occur even if the exploiter or mutualist alone cannot mediate the coexistence of two resources. We conclude that the coexistence of mutualism and antagonism may be the key to the persistence of the four-species module in the presence of adaptive switching.