Parasite transmission modes and the evolution of virulence

A mathematical model is presented that explores the relationship between transmission patterns and the evolution of virulence for horizontally transmitted parasites when only a single parasite strain can infect each host. The model is constructed by decomposing parasite transmission into two processes, the rate of contact between hosts and the probability of transmission per contact. These transmission rate components, as well as the total parasite mortality rate, are allowed to vary over the course of an infection. A general evolutionarily stable condition is presented that partitions the effects of virulence on parasite fitness into three components: fecundity benefits, mortality costs, and morbidity costs. This extension of previous theory allows us to explore the evolutionary consequences of a variety of transmission patterns. I then focus attention on a special case in which the parasite density remains approximately constant during an infection, and I demonstrate two important ways in which transmission modes can affect virulence evolution: by imposing different morbidity costs on the parasite and by altering the scheduling of parasite reproduction during an infection. Both are illustrated with examples, including one that examines the hypothesis that vector-borne parasites should be more virulent than non-vector-borne parasites (Ewald 1994). The validity of this hypothesis depends upon the way in which these two effects interact, and it need not hold in general.     

Pathogen clumping: an explanation for non-linear transmission of an insect virus

Abstract.  1. Previous work has shown that transmission of some insect pathogens is a non-linear process. A number of hypotheses have been put forward as explanations for this phenomenon; however, none have proven wholly satisfactory. Here we test the effects on transmission of spatial distribution of an insect virus by testing whether or not experimental manipulations of pathogen clumping lead to different values of a clumping parameter. The gypsy moth nucleopolyhedrovirus (LdMNPV) was used, which is transmitted when larvae consume virus released from previously infected larvae that have died on foliage.
2. It was found that even when virus densities on foliage were equal, overall mortality was lower when virus-killed cadavers were clumped on foliage.
3. Non-linearity is more pronounced when cadavers are clumped than when they are placed at random on the foliage. Placement of droplets containing LdMNPV on foliage resulted in more linear transmission compared with cadavers.
4. Spatial clumping of viral inoculum thus provides part of the explanation for non-linear transmission in this system. The ultimate explanation for non-linear transmission is likely to involve some combination of spatial clumping and heterogeneity in behaviours such as feeding rate or the ability to avoid pathogen.     

The evolution of virulence in pathogens with frequency-dependent transmission

Frequency-dependent transmission is an important feature of diseases that are sexually transmitted or transmitted by a vector that actively searches for hosts. Here I describe the evolution of virulence in pathogens that have frequency-dependent transmission. I consider two components of virulence--an increase in host mortality due to infection, as is classically described, and a decrease in host fecundity due to infection, because frequency dependence is common among diseases that fully or partially sterilize their hosts. Theoretical predictions pertaining to host-pathogen numerical dynamics can be quite different between pathogens with frequency-dependent transmission and those with density-dependent transmission. In contrast, this study suggests that the principles governing the evolution of virulence that have been established in the context of density-dependent pathogens may also apply (qualitatively) to frequency-dependent pathogens. I examine the evolutionary trajectories of the mortality and sterility components of virulence as well as the role of spatial population structure in the evolution of the sterility component of virulence.     

The insect transmission of an isolate of okra mosaic virus occurring in Nigeria

Three species of chrysomelid beetles (Podagrica sjostedti, P. uniforma and Syagrus calcaratus) transmitted a Nigerian isolate of okra mosaic virus (OMV) to okra (Abelmoschus esculentus) and green gram (Vigna aureus), two (P. uniforma and S. calcaratus) also to cotton (Gossypium hirsutum) and one (P. uniforma) also to cowpea. Using one viruliferous beetle per test plant, P. sjostedti, P. uniforma and S. calcaratus infected 63, 68 and 34% of test plants respectively. Virus was retained by these vectors for up to 6 days. Whiteflies (Bemisia tabaci) also transmitted OMV, although much less efficiently than the beetle vectors.     

Mixed genotype transmission bodies and virions contribute to the maintenance of diversity in an insect virus

An insect nucleopolyhedrovirus naturally survives as a mixture of at least nine genotypes. Infection by multiple genotypes results in the production of virus occlusion bodies (OBs) with greater pathogenicity than those of any genotype alone. We tested the hypothesis that each OB contains a genotypically diverse population of virions. Few insects died following inoculation with an experimental two-genotype mixture at a dose of one OB per insect, but a high proportion of multiple infections were observed (50%), which differed significantly from the frequencies predicted by a non-associated transmission model in which genotypes are segregated into distinct OBs. By contrast, insects that consumed multiple OBs experienced higher mortality and infection frequencies did not differ significantly from those of the non-associated model. Inoculation with genotypically complex wild-type OBs indicated that genotypes tend to be transmitted in association, rather than as independent entities, irrespective of dose. To examine the hypothesis that virions may themselves be genotypically heterogeneous, cell culture plaques derived from individual virions were analysed to reveal that one-third of virions was of mixed genotype, irrespective of the genotypic composition of the OBs. We conclude that co-occlusion of genotypically distinct virions in each OB is an adaptive mechanism that favours the maintenance of virus diversity during insect-to-insect transmission.     

The evolution of virulence in a plant virus

Abstract The evolution of virulence is a rapidly growing field of research, but few reports deal with the evolution of virulence in natural populations of parasites. We present here an observational and experimental analysis of the evolution of virulence of the plant virus Cucumber mosaic virus (CMV) during an epidemic on tomato in eastern Spain. Three types of CMV isolates were found that caused in tomato plants either a systemic necrosis (N isolates), stunting and a severe reduction of leaf lamina (Y isolates), or stunting and leaf curl (A isolates). These phenotypes were due to the presence of satellite RNAs (satRNAs) necrogenic (in N isolates) or attenuative (in A isolates) of the symptoms caused by CMV without satRNA (Y isolates). For these three types of isolates, parameters of virulence and transmission were estimated experimentally. For virulence the ranking of isolates was N < Y < A, for trans-missibility, Y < A < N. The predictions of theoretical models for the evolution of virulence were analyzed with these parameters and compared with observations from the field. A single-infection model predicted adequately the observed long-term evolution of the CMV population to intermediate levels of virulence. A coinfection model that considered competition between isolates with an effect on transmission explained the invasion of the CMV population by N isolates at the beginning of the epidemic, and its predictions also agreed with field data on the long-term evolution of the CMV population. An important conclusion from both models was that the density of the aphid vector's population is a major factor in the evolution of CMV virulence. This may be relevant for the design of control strategies for CMV-induced diseases.     

昆虫介体行为与植物病毒的传播

大多数植物病毒都是依赖昆虫介体进行传播,其中超过80%的传毒介体昆虫都是属于半翅目同翅亚目。昆虫介体识别寄主植物和取食的过程与病毒的传播密切相关,本文主要综述了同翅亚目昆虫、蓟马等介体昆虫取食行为与植物病毒的相互作用方面的研究进展,着重于介绍昆虫不同取食阶段的行为对植物病毒传播的影响,病毒侵染对介体取食和识别寄主行为的影响。     

Density-independent resource limitation and the transmission of an insect pathogen

The effects of resource limitation on the transmission of a pathogen were explored. Resource limitation was achieved by replacing part of the host’s diet with an indigestible bulking agent. Populations of the pyrallid moth, Plodia interpunctella, raised on high- and low-quality food regimes were exposed to a granulosis virus. Moths subjected to a lower food quality were more likely to become infected, despite the fact that in previous studies, individuals showed no increased susceptibility when exposed individually to the virus. This effect is suggested to be due to a higher exposure to the pathogen due to a faster feeding rate and longer developmental period. The implications of resource levels to the population dynamics of host-pathogen interactions are discussed. Received: 8 July 1999 / Accepted: 14 February 2000     

Molecular and biochemical studies of the evolution, infection and transmission of insect bunyaviruses

Members of the Bunyaviridae family of RNA viruses (bunyaviruses, hantaviruses, nairoviruses, phleboviruses and uukuviruses) have been studied at the molecular and genetic level to understand the basis of their evolution and infection in vertebrate and invertebrate (arthropod) hosts. With the exception of the hantaviruses, these viruses infect and are transmitted by a variety of blood-sucking arthropods (mosquitoes, phlebotomines, gnats, ticks, etc.). The viruses are responsible for infection of various vertebrate species, occasionally causing human disease, morbidity and mortality (e.g. Rift Valley fever, Crimean-Congo haemorrhagic fever, Korean haemorrhagic fever). Genetic and molecular analyses of bunyaviruses have established the coding assignments of the three viral RNA species and documented which viral gene products determine host range and virulence. Ecological studies, with molecular techniques, have provided evidence for bunyavirus evolution in nature through genetic drift (involving the accumulation of point mutations) and shift (RNA-segment reassortment).     

An empirical study of the evolution of virulence under both horizontal and vertical transmission

According to current thinking, a parasite's transmission mode will be a major determinant of virulence, defined as the harm induced by parasites to their hosts. With horizontal transmission, virulence will increase as a byproduct of a trade-off between fitness gained through increased among-host transmission (infectivity) and fitness lost through increased virulence. With vertical transmission, virulence will decrease because a parasite's reproductive potential will be maximized only by decreasing harm to the host, allowing parasite transmission to more host offspring. To test both predictions, we transmitted barley stripe mosaic virus (BSMV) horizontally and then vertically in its host, barley (Hordeum vulgare). After four generations of horizontal transmission, we observed a nearly twofold increase in horizontal infectivity and nearly tripled virulence. After three generations of subsequent vertical transmission, we observed a modest (16%) increase in vertical transmissibility and a large (40%) reduction in virulence. Increased horizontal transmission is often due to increased pathogen replication which, in turn, causes increased virulence. However, we found no correlation between within-host virus concentration and virulence, indicating that the observed changes in virulence were not due to changes in viral titer. Finally, horizontally transmitted BSMV had reduced vertical transmission and vertically transmitted BSMV had reduced horizontal infectivity. These two observations suggest that, in nature, in different host populations with varying opportunities for horizontal and vertical transmission, different viral strains may be favored.     

Neuromuscular transmission in an insect visceral muscle

The electrical properties of the muscles of locust oviduct have been examined using intracellular recordings. The muscle cells are both dye and electrically coupled. They possess a wide array of spontaneous electrical activity ranging from slow oscillations of membrane potential to action potentials. In addition to possessing spontaneous electrical activity, certain regions of the oviduct are under motor control. The amplitude of evoked excitatory junction potentials (EJPs) increased step wise revealing innervation from a maximum of three motor units. These EJPs underwent summation and facilitation, and reached a critical threshold at which point the membrane revealed an active response. Bath applied glutamate, aspartate, proctolin, and octopamine were tested for their ability to alter resting potential and EJPs. L-glutamate (1.6 X 10(-5) M and above) produced a dose-dependent depolarization of membrane potential accompanied by a reduction in amplitude of EJPs. Although L-aspartate resulted in similar effects, the concentrations required were higher than those for glutamate. Proctolin (6.3 X 10(-11) M-6.0 X 10(-9) M) resulted in a dose-dependent depolarization but had little or no effect on amplitude of EJPs. Application of D, L-octopamine (3.2 X 10(-5) M-1.7 X 10(-4) M) induced a small hyperpolarization and a reduction in amplitude of EJP. It is suggested that contractions of locust oviduct appear to be regulated by a combination of a classical neurotransmitter such as glutamate, along with the neuromodulators octopamine and proctolin.     

The evolution of parasite virulence and transmission rate in a spatially structured population

If the transmission occurs through local contact of the individuals in a spatially structured population, the evolutionarily stable (ESS) traits of parasite might be quite different from what the classical theory with complete mixing predicts. In this paper, we theoretically study the ESS virulence and transmission rate of a parasite in a lattice-structured host population, in which the host can send progeny only to its neighboring vacant site, and the transmission occurs only in between the infected and the susceptible in the nearest-neighbor sites. Infected host is assumed to be infertile. The analysis based on the pair approximation and the Monte Carlo simulation reveal that the ESS transmission rate and virulence in a lattice-structured population are greatly reduced from those in completely mixing population. Unlike completely mixing populations, the spread of parasite can drive the host to extinction, because the local density of the susceptible next to the infected can remain high even when the global density of host becomes very low. This demographic viscosity and group selection between self-organized spatial clusters of host individuals then leads to an intermediate ESS transmission rate even if there is no tradeoff between transmission rate and virulence. The ESS transmission rate is below the region of parasite-driven extinction by a finite amount for moderately large reproductive rate of host; whereas, the evolution of transmission rate leads to the fade out of parasite for small reproductive rate, and the extinction of host for very large reproductive rate.     

Trade-offs in the evolution of virulence in an indirectly transmitted macroparasite

The adaptive trade-off theory for the evolution and maintenance of parasite virulence requires that virulence be genetically correlated with other fitness characteristics of the parasite. Many theoretical models rely on a positive correlation between virulence and transmissibility. They assume that high parasite replication rates are associated with a high probability of transmission (and, hence, increased parasite fitness), but also with high levels of damage to the host (high virulence). Schistosomes are macroparasites with an indirect life cycle involving a mammalian and a molluscan host. Here we demonstrate, through the development of five substrains, a genetic basis for schistosome virulence. We used these substrains further in order to investigate the presence of parasite fitness traits that were genetically correlated with virulence. High virulence in the (mouse) definitive host was, as predicted, positively correlated with parasite replication. In contrast, in the (snail) intermediate host high virulence was associated with low parasite replication rates. Variation in infectivity to and parasite replication in the definitive host was suggested as a compensating mechanism for the maintenance of virulence in the snail host. This is the first report of a trade-off in parasite reproductive success across hosts in an indirectly transmitted macroparasite.     

Four amino acids of an insect densovirus capsid determine midgut tropism and virulence

Densoviruses are insect parvoviruses that are orally infectious for Lepidoptera. To assess the mechanisms underlying their specificity and their virulence, we investigated the role of eight candidate residues in the densovirus capsid. We showed that the substitutions of four amino acids were associated with decreased virulence due to a decreased ability to cross the host midgut epithelium, without an effect on viral replication in other tissues.     

Increased insect virulence in Beauveria bassiana strains overexpressing an engineered chitinase

Entomopathogenic fungi are currently being used for the control of several insect pests as alternatives or supplements to chemical insecticides. Improvements in virulence and speed of kill can be achieved by understanding the mechanisms of fungal pathogenesis and genetically modifying targeted genes, thus improving the commercial efficacy of these biocontrol agents. Entomopathogenic fungi, such as Beauveria bassiana, penetrate the insect cuticle utilizing a plethora of hydrolytic enzymes, including chitinases, which are important virulence factors. Two chitinases (Bbchit1 and Bbchit2) have previously been characterized in B. bassiana, neither of which possesses chitin-binding domains. Here we report the construction and characterization of several B. bassiana hybrid chitinases where the chitinase Bbchit1 was fused to chitin-binding domains derived from plant, bacterial, or insect sources. A hybrid chitinase containing the chitin-binding domain (BmChBD) from the silkworm Bombyx mori chitinase fused to Bbchit1 showed the greatest ability to bind to chitin compared to other hybrid chitinases. This hybrid chitinase gene (Bbchit1-BmChBD) was then placed under the control of a fungal constitutive promoter (gpd-Bbchit1-BmChBD) and transformed into B. bassiana. Insect bioassays showed a 23% reduction in time to death in the transformant compared to the wild-type fungus. This transformant also showed greater virulence than another construct (gpd-Bbchit1) with the same constitutive promoter but lacking the chitin-binding domain. We utilized a strategy where genetic components of the host insect can be incorporated into the fungal pathogen in order to increase host cuticle penetration ability.     

Kin selection and the evolution of virulence

Social interactions between conspecific parasites are partly dependent on the relatedness of interacting parasites (kin selection), which, in turn, is predicted to affect the extent of damage they cause their hosts (virulence). High relatedness is generally assumed to favour less competitive interactions, but the relationship between relatedness and virulence is crucially dependent on the social behaviour in question. Here, we discuss the rather limited body of experimental work that addresses how kin-selected social behaviours affect virulence. First, if prudent use of host resources (a form of cooperation) maximizes the transmission success of the parasite population, decreased relatedness is predicted to result in increased host exploitation and virulence. Experimental support for this well-established theoretical result is surprisingly limited. Second, if parasite within-host growth rate is a positive function of cooperation (that is, when individuals need to donate public goods, such as extracellular enzymes), virulence is predicted to increase with increasing relatedness. The limited studies testing this hypothesis are broadly consistent with this prediction. Finally, there is some empirical evidence supporting theory that suggests that spiteful behaviours are maximized at intermediate degrees of relatedness, which, in turn, leads to minimal virulence because of the reduced growth rate of the infecting population. We highlight the need for further thorough experimentation on the role of kin selection in the evolution of virulence and identify additional biological complexities to these simple frameworks.