Expanding host specificity and pathogen sharing beyond viruses

Most emerging pathogens of humans can infect multiple host species (Woolhouse & Gowtage‐Sequeria, 2005). This simple fact has motivated multiple large‐scale, comparative analyses of the drivers of pathogen sharing and zoonotic pathogen richness among hosts as well as the factors determining the zoonotic potential of pathogens themselves. However, most of this work focuses on viruses, limiting a broader understanding of how host range varies within and between pathogen groups. In this issue of Molecular Ecology, Shaw et al. (2020) compile a comprehensive data set of host–pathogen associations across viruses and bacteria and test whether previous patterns observed in the former occur in the latter. They find most viruses and bacteria are specialists, and viruses are more likely to be generalists; however, generalist bacteria encompass multiple host orders, whereas viral sharing occurs more within host orders. Lastly, the authors demonstrate that many factors previously identified as predictors of zoonotic richness for viruses occur for bacteria and that host phylogenetic similarity is a primary determinant of cross‐species transmission. However, pathogen sharing with humans was more common and more weakly related to phylogenetic distance to Homo sapiens for bacteria compared to viruses, suggesting the former could pose greater spillover risks across host orders. This work represents a key advance in our understanding of host specificity and pathogen sharing beyond viruses.     

Ecological and evolutionary drivers of haemoplasma infection and bacterial genotype sharing in a Neotropical bat community

Most emerging pathogens can infect multiple species, underlining the importance of understanding the ecological and evolutionary factors that allow some hosts to harbour greater infection prevalence and share pathogens with other species. However, our understanding of pathogen jumps is based primarily around viruses, despite bacteria accounting for the greatest proportion of zoonoses. Because bacterial pathogens in bats (order Chiroptera) can have conservation and human health consequences, studies that examine the ecological and evolutionary drivers of bacterial prevalence and barriers to pathogen sharing are crucially needed. Here were studied haemotropic Mycoplasma spp. (i.e., haemoplasmas) across a species‐rich bat community in Belize over two years. Across 469 bats spanning 33 species, half of individuals and two‐thirds of species were haemoplasma positive. Infection prevalence was higher for males and for species with larger body mass and colony sizes. Haemoplasmas displayed high genetic diversity (21 novel genotypes) and strong host specificity. Evolutionary patterns supported codivergence of bats and bacterial genotypes alongside phylogenetically constrained host shifts. Bat species centrality to the network of shared haemoplasma genotypes was phylogenetically clustered and unrelated to prevalence, further suggesting rare—but detectable—bacterial sharing between species. Our study highlights the importance of using fine phylogenetic scales when assessing host specificity and suggests phylogenetic similarity may play a key role in host shifts not only for viruses but also for bacteria. Such work more broadly contributes to increasing efforts to understand cross‐species transmission and the epidemiological consequences of bacterial pathogens.     

Integrating phylogenetic and ecological distances reveals new insights into parasite host specificity

The range of hosts a pathogen infects (host specificity) is a key element of disease risk that may be influenced by both shared phylogenetic history and shared ecological attributes of prospective hosts. Phylospecificity indices quantify host specificity in terms of host relatedness, but can fail to capture ecological attributes that increase susceptibility. For instance, similarity in habitat niche may expose phylogenetically unrelated host species to similar pathogen assemblages. Using a recently proposed method that integrates multiple distances, we assess the relative contributions of host phylogenetic and functional distances to pathogen host specificity (functional–phylogenetic host specificity). We apply this index to a data set of avian malaria parasite (Plasmodium and Haemoproteus spp.) infections from Melanesian birds to show that multihost parasites generally use hosts that are closely related, not hosts with similar habitat niches. We also show that host community phylogenetic ß‐diversity (Pßd) predicts parasite Pßd and that individual host species carry phylogenetically clustered Haemoproteus parasite assemblages. Our findings were robust to phylogenetic uncertainty, and suggest that phylogenetic ancestry of both hosts and parasites plays important roles in driving avian malaria host specificity and community assembly. However, restricting host specificity analyses to either recent or historical timescales identified notable exceptions, including a ‘habitat specialist’ parasite that infects a diversity of unrelated host species with similar habitat niches. This work highlights that integrating ecological and phylogenetic distances provides a powerful approach to better understand drivers of pathogen host specificity and community assembly.     

Phylogeny and geography predict pathogen community similarity in wild primates and humans

In natural systems, host species are often co-infected by multiple pathogen species, and recent work has suggested that many pathogens can infect a wide range of host species. An important question therefore is what determines the host range of a pathogen and the community of pathogens found within a given host species. Using primates as a model, we show that infectious diseases are more often shared between species that are closely related and inhabit the same geographical region. We find that host relatedness is the best overall predictor of whether two host species share the same pathogens. A higher frequency of pathogen host shifts between close relatives or inheritance of pathogens from a common ancestor may explain this result. For viruses, geographical overlap among neighbouring primate hosts is more important in determining host range. We suggest this is because rapid evolution within viral lineages allows host jumps across larger evolutionary distances. We also show that the phylogenetic pattern of pathogen sharing with humans is the same as that between wild primates. For humans, this means we share a higher proportion of pathogens with the great apes, including chimpanzees and gorillas, because these species are our closest relatives.     

Diseases of humans and their domestic mammals: pathogen characteristics, host range and the risk of emergence

Pathogens that can be transmitted between different host species are of fundamental interest and importance from public health, conservation and economic perspectives, yet systematic quantification of these pathogens is lacking. Here, pathogen characteristics, host range and risk factors determining disease emergence were analysed by constructing a database of disease-causing pathogens of humans and domestic mammals. The database consisted of 1415 pathogens causing disease in humans, 616 in livestock and 374 in domestic carnivores. Multihost pathogens were very prevalent among human pathogens (61.6%) and even more so among domestic mammal pathogens (livestock 77.3%, carnivores 90.0%). Pathogens able to infect human, domestic and wildlife hosts contained a similar proportion of disease-causing pathogens for all three host groups. One hundred and ninety-six pathogens were associated with emerging diseases, 175 in humans, 29 in livestock and 12 in domestic carnivores. Across all these groups, helminths and fungi were relatively unlikely to emerge whereas viruses, particularly RNA viruses, were highly likely to emerge. The ability of a pathogen to infect multiple hosts, particularly hosts in other taxonomic orders or wildlife, were also risk factors for emergence in human and livestock pathogens. There is clearly a need to understand the dynamics of infectious diseases in complex multihost communities in order to mitigate disease threats to public health, livestock economies and wildlife.     

Phylogenetic determinants of potential host shifts in fungal pathogens

Understanding what determines the host range of pathogens and the potential for host shifts is of critical importance to controlling their introductions into new environments. The phylogeny of the hosts has been shown to be important: pathogens are more likely to be infectious on hosts closely related to their host‐of‐origin because of the similar host environments that is shared by descent. The importance of pathogen phylogenies for predicting host range has never been investigated, although a pathogen should also be able to exploit a new host that its close relative can infect. We performed cross‐inoculations using a plant–fungal association and showed that both host and pathogen phylogenies were significant predictors of host range, with at least partly independent effects. Furthermore, we showed that some pathogens were better at infecting novel hosts. Our results should have implications in the context of biological invasions and emergences of new diseases due to globalization.     

Ecological factors driving the long-term evolution of influenza's host range

The evolution of a pathogen''s host range is shaped by the ecology of its hosts and by the physiological traits that determine host specificity. For many pathogen traits, there is a trade-off: a phenotype suitable for infecting one set of hosts poorly infects another. Introducing and analysing a simple evo-epidemiological model, here we study how such a trade-off is expected to affect evolution of the host ranges of influenza viruses. We examine a quantitative trait underlying host specificity, given by an influenza virus''s degree of adaptation to certain conformations of sialic acid receptors, and investigate how this receptor preference evolves in a minimal network of host species, including humans, that differ in life history and receptor physiology. Using adaptive dynamics theory, we establish thresholds in interspecific transmission rates and host population sizes that govern the emergence and persistence of human-adapted viruses. These ecological thresholds turn out to be largely independent of the strength of the evolutionary trade-off, underscoring the importance of ecological conditions in determining a disease''s host range.     

A SIMPLE MODEL EXPLAINS THE DYNAMICS OF PREFERENTIAL HOST SWITCHING AMONG MAMMAL RNA VIRUSES

A growing number of studies support a tendency toward preferential host switching, by parasites and pathogens, over relatively short phylogenetic distances. This suggests that a host switch is more probable if a potential host is closely related to the original host than if it is a more distant relative. However, despite its importance for the health of humans, livestock, and wildlife, the detailed dynamics of preferential host switching have, so far, been little studied. We present an empirical test of two theoretical models of preferential host switching, using observed phylogenetic distributions of host species for RNA viruses of three mammal orders (primates, carnivores, and ungulates). The analysis focuses on multihost RNA virus species, because their presence on multiple hosts and their estimated ages of origin indicate recent host switching. Approximate Bayesian computation was used to compare observed phylogenetic distances between hosts with those simulated under the theoretical models. The results support a decreasing sigmoidal model of preferential host switching, with a strong effect from increasing phylogenetic distance, on all three studied host phylogenies. This suggests that the dynamics of host switching are fundamentally similar for RNA viruses of different mammal orders and, potentially, a wider range of coevolutionary systems.     

Marked host specificity and lack of phylogeographic population structure of Campylobacter jejuni in wild birds

Zoonotic pathogens often infect several animal species, and gene flow among populations infecting different host species may affect the biological traits of the pathogen including host specificity, transmissibility and virulence. The bacterium Campylobacter jejuni is a widespread zoonotic multihost pathogen, which frequently causes gastroenteritis in humans. Poultry products are important transmission vehicles to humans, but the bacterium is common in other domestic and wild animals, particularly birds, which are a potential infection source. Population genetic studies of C. jejuni have mainly investigated isolates from humans and domestic animals, so to assess C. jejuni population structure more broadly and investigate host adaptation, 928 wild bird isolates from Europe and Australia were genotyped by multilocus sequencing and compared to the genotypes recovered from 1366 domestic animal and human isolates. Campylobacter jejuni populations from different wild bird species were distinct from each other and from those from domestic animals and humans, and the host species of wild bird was the major determinant of C. jejuni genotype, while geographic origin was of little importance. By comparison, C. jejuni differentiation was restricted between more phylogenetically diverse farm animals, indicating that domesticated animals may represent a novel niche for C. jejuni and thereby driving the evolution of those bacteria as they exploit this niche. Human disease is dominated by isolates from this novel domesticated animal niche.     

Understanding host utilization by mosquitoes: determinants,challenges and future directions

Mosquito host utilization is a key factor in the transmission of vector-borne pathogens given that it greatly influences host–vector contact rates. Blood-feeding patterns of mosquitoes are not random, as some mosquitoes feed on particular species and/or individuals more than expected by chance. Mosquitoes use a number of cues including visual, olfactory, acoustic, and thermal stimuli emitted by vertebrate hosts to locate and identify their blood meal sources. Thus, differences in the quality/intensity of the released cues may drive host selection by mosquitoes at both inter- and intra-specific levels. Such patterns of host selection by mosquitoes in space and time can be structured by factors related to mosquitoes (e.g. innate host preference, behavioural plasticity), to hosts (e.g. emission of host-seeking cues, host availability) or to both (e.g. pathogen infection). In this study, we review current evidence, from phenomena to mechanisms, of how these factors influence host utilization by mosquitoes. We also review the methodologies commonly used in this research field and identify the major challenges for future studies. To bridge the knowledge gaps, we propose improvements to strengthen traditional approaches and the use of a functional trait-based approach to infer mosquito host utilization in natural communities.     

Shifts in diversification rates and host jump frequencies shaped the diversity of host range among Sclerotiniaceae fungal plant pathogens

The range of hosts that a parasite can infect in nature is a trait determined by its own evolutionary history and that of its potential hosts. However, knowledge on host range diversity and evolution at the family level is often lacking. Here, we investigate host range variation and diversification trends within the Sclerotiniaceae, a family of Ascomycete fungi. Using a phylogenetic framework, we associate diversification rates, the frequency of host jump events and host range variation during the evolution of this family. Variations in diversification rate during the evolution of the Sclerotiniaceae define three major macro‐evolutionary regimes with contrasted proportions of species infecting a broad range of hosts. Host–parasite cophylogenetic analyses pointed towards parasite radiation on distant hosts long after host speciation (host jump or duplication events) as the dominant mode of association with plants in the Sclerotiniaceae. The intermediate macro‐evolutionary regime showed a low diversification rate, high frequency of duplication events and the highest proportion of broad host range species. Our findings suggest that the emergence of broad host range fungal pathogens results largely from host jumps, as previously reported for oomycete parasites, probably combined with low speciation rates. These results have important implications for our understanding of fungal parasites evolution and are of particular relevance for the durable management of disease epidemics.     

Factors affecting host range in a generalist seed pathogen of semi-arid shrublands

Generalist pathogens can exhibit differential success on different hosts, resulting in complex host range patterns. Several factors operate to reduce realized host range relative to potential host range, particularly under field conditions. We explored factors influencing host range of the naturally occurring generalist ascomycete grass seed pathogen Pyrenophora semeniperda. We measured potential host range in laboratory experiments at high inoculum loads with 26 grass species, including the primary host Bromus tectorum, and developed models to predict susceptibility and tolerance based on host traits, including germination speed, seed hardness, seed size, and phylogenetic relations. We also examined pathogen and host density effects on infection and mortality. All species tested were at least somewhat susceptible to the pathogen at high inoculum loads, but both infection and mortality varied widely. Species more closely related to the original host (B. tectorum) were more susceptible to infection, whereas species with slower germination were less tolerant and therefore more likely to suffer mortality. Infection and mortality were sharply reduced as inoculum load was reduced. Intermediate loads had major negative impacts on dormant B. tectorum seeds but generally minimal effects on native species. In addition, field seed bank studies determined that P. semeniperda rarely exploits native grass species as hosts. This marked reduction in realized host range relative to potential host range indicates that laboratory host range studies are potentially a poor predictor of either the current or possible future realized host range for wildland plant pathogens.     

Evolution of pathogen virulence: the role of variation in host phenotype

Selection on pathogens tends to favour the evolution of growth and reproductive rates and a concomitant level of virulence (damage done to the host) that maximizes pathogen fitness. Yet, because hosts often pose varying selective environments to pathogens, one level of virulence may not be appropriate for all host types. Indeed, if a level of virulence confers high fitness to the pathogen in one host phenotype but low fitness in another host phenotype, alternative virulence strategies may be maintained in the pathogen population. Such strategies can occur either as polymorphism, where different strains of pathogen evolve specialized virulence strategies in different host phenotypes or as polyphenism, where pathogens facultatively express alternative virulence strategies depending on host phenotype. Polymorphism potentially leads to specialist pathogens capable of infecting a limited range of host phenotypes, whereas polyphenism potentially leads to generalist pathogens capable of infecting a wider range of hosts. Evaluating how variation among hosts affects virulence evolution can provide insight into pathogen diversity and is critical in determining how host pathogen interactions affect the phenotypic evolution of both hosts and pathogens.     

Climate variation influences host specificity in avian malaria parasites

Parasites with low host specificity (e.g. infecting a large diversity of host species) are of special interest in disease ecology, as they are likely more capable of circumventing ecological or evolutionary barriers to infect new hosts than are specialist parasites. Yet for many parasites, host specificity is not fixed and can vary in response to environmental conditions. Using data on host associations for avian malaria parasites (Apicomplexa: Haemosporida), we develop a hierarchical model that quantifies this environmental dependency by partitioning host specificity variation into region‐ and parasite‐level effects. Parasites were generally phylogenetic host specialists, infecting phylogenetically clustered subsets of available avian hosts. However, the magnitude of this specialisation varied biogeographically, with parasites exhibiting higher host specificity in regions with more pronounced rainfall seasonality and wetter dry seasons. Recognising the environmental dependency of parasite specialisation can provide useful leverage for improving predictions of infection risk in response to global climate change.     

CpG Dinucleotide Frequencies Reveal the Role of Host Methylation Capabilities in Parvovirus Evolution

Parvoviruses are rapidly evolving viruses that infect a wide range of hosts, including vertebrates and invertebrates. Extensive methylation of the parvovirus genome has been recently demonstrated. A global pattern of methylation of CpG dinucleotides is seen in vertebrate genomes, compared to “fractional” methylation patterns in invertebrate genomes. It remains unknown if the loss of CpG dinucleotides occurs in all viruses of a given DNA virus family that infect host species spanning across vertebrates and invertebrates. We investigated the link between the extent of CpG dinucleotide depletion among autonomous parvoviruses and the evolutionary lineage of the infected host. We demonstrate major differences in the relative abundance of CpG dinucleotides among autonomous parvoviruses which share similar genome organization and common ancestry, depending on the infected host species. Parvoviruses infecting vertebrate hosts had significantly lower relative abundance of CpG dinucleotides than parvoviruses infecting invertebrate hosts. The strong correlation of CpG dinucleotide depletion with the gain in TpG/CpA dinucleotides and the loss of TpA dinucleotides among parvoviruses suggests a major role for CpG methylation in the evolution of parvoviruses. Our data present evidence that links the relative abundance of CpG dinucleotides in parvoviruses to the methylation capabilities of the infected host. In sum, our findings support a novel perspective of host-driven evolution among autonomous parvoviruses.     

Viral adaptation to host: a proteome‐based analysis of codon usage and amino acid preferences

Viruses differ markedly in their specificity toward host organisms. Here, we test the level of general sequence adaptation that viruses display toward their hosts. We compiled a representative data set of viruses that infect hosts ranging from bacteria to humans. We consider their respective amino acid and codon usages and compare them among the viruses and their hosts. We show that bacteria‐infecting viruses are strongly adapted to their specific hosts, but that they differ from other unrelated bacterial hosts. Viruses that infect humans, but not those that infect other mammals or aves, show a strong resemblance to most mammalian and avian hosts, in terms of both amino acid and codon preferences. In groups of viruses that infect humans or other mammals, the highest observed level of adaptation of viral proteins to host codon usages is for those proteins that appear abundantly in the virion. In contrast, proteins that are known to participate in host‐specific recognition do not necessarily adapt to their respective hosts. The implication for the potential of viral infectivity is discussed.     

The dynamics of preferential host switching: Host phylogeny as a key predictor of parasite distribution*

Parasites often jump to and become established in a new host species. There is much evidence that the probability of such host shifts decreases with increasing phylogenetic distance between donor and recipient hosts, but the consequences of such preferential host switching remain little explored. We develop a computational model to investigate the dynamics of parasite host shifts in the presence of this phylogenetic distance effect. In this model, a clade of parasites evolves on an evolving clade of host species where parasites can cospeciate with their hosts, switch to new hosts, speciate within hosts or become extinct. Our model predicts that host phylogenies are major determinants of parasite distributions across trees. In particular, we predict that trees consisting of few large clades of host species and those with fast species turnover should harbor more parasites than trees with many small clades and those that diversify more slowly. Within trees, large clades are predicted to exhibit a higher fraction of infected species than small clades. We discuss our results in the light of recent cophylogenetic studies in a wide range of host–parasite systems.     

Kaposi's sarcoma associated herpesvirus G-protein coupled receptor activation of cyclooxygenase-2 in vascular endothelial cells

Background

Taking as a pattern, the T4 and lambda viruses interacting with each other and with their Gram-negative host, Escherichia coli, a general model is constructed for the evolution of 'gentle' or temperate pathogens. This model is not simply either pure group or kin selection, but probably is common in a variety of host-parasite pairs in various taxonomic groups. The proposed mechanism is that for its own benefit the pathogen evolved ways to protect its host from attack by other pathogens and this has incidentally protected the host. Although appropriate mechanisms would have been developed and excluded related viral species and also other quite different pathogens, the important advance would have been when other individuals of the same species that arrive at the host subsequent to the first infecting one were excluded.

Results

Such a class of mechanisms would not compete one genotype with another, but simply would be of benefit to the first pathogen that had attacked a host organism.

Conclusion

This would tend to protect and extend the life of the host against the detrimental effects of a secondarily infecting pathogen. This leads to the pathogens becoming more temperate via the now favorable co-evolution with its host, which basically protects both host and virus against other pathogens but may cause slowing of the growth of the primary infecting pathogen. Evolution by a 'gentle' strategy would be favored as long as the increased wellbeing of the host also favored the eventual transmission of the early infecting pathogen to other hosts.     

Maternal transfer of strain-specific immunity in an invertebrate

The most celebrated component of the vertebrate immune system is the acquired response in which memory cells established during primary infection enhance the proliferation of antibodies during secondary infection. Additionally, the strength of vertebrate acquired immune responses varies dramatically depending on the infecting pathogen species or on the pathogen genotype within species. Because invertebrates lack the T-cell receptors and Major Histocompatibility Complex (MHC) molecules that mediate vertebrate adaptive immune responses, they are thought to lack adaptive immunity and be relatively unspecific in their interactions with pathogens. With only innate immunity, invertebrate hosts are believed to be nai;ve at each new encounter with pathogens. Nevertheless, some forms of facultative immunity appear to be important in insects; some individuals have enhanced immunity due to population density, and some social insects benefit when their nest-mates have been exposed to a pathogen or pathogen mimic (; see for a predation example.) Here we provide evidence for acquired strain-specific immunity in the crustacean Daphnia magna infected with the pathogenic bacteria Pasteuria ramosa. Specifically, the fitness of hosts was enhanced when challenged with a bacterial strain their mother had experienced relative to cases when mother and offspring were challenged with different strains.