Host factors exploited by retroviruses

Retroviruses make a long and complex journey from outside the cell to the nucleus in the early stages of infection, and then an equally long journey back out again in the late stages of infection. Ongoing efforts are identifying an enormous array of cellular proteins that are used by the viruses in the course of their travels. These host factors are potential new targets for therapeutic intervention.     

Host choice and penetration by Schistosoma haematobium miracidia

Schistosome parasites commonly show specificity to their intermediate mollusc hosts and the degree of specificity can vary between parasite strains and geographical location. Here the role of miracidial behaviour in host specificity of Schistosoma haematobium on the islands of Zanzibar is investigated. In choice-chamber experiments, S. haematobium miracidia moved towards Bulinus globosus snail hosts in preference to empty chambers. In addition, miracidia preferred uninfected over patent B. globosus. This preference should benefit the parasite as patent snails are likely to have mounted an immune response to S. haematobium as well as providing poorer resources than uninfected snails. Miracidia also discriminated between the host B. globosus and the sympatric, non-host species Cleopatra ferruginea. In contrast, S. haematobium did not discriminate against the allopatric Bulinus nasutus. Penetration of the host by miracidia was investigated by screening snails 24 h after exposure using polymerase chain reaction (PCR) with S. haematobium specific DraI repeat primers. There was no difference in the frequency of penetration of B. globosus versus B. nasutus. These responses to different snail species may reflect selection pressure to avoid sympatric non-hosts which represent a transmission dead end. The distribution of B. nasutus on Unguja is outside the endemic zone and so there is less chance of exposure to S. haematobium, hence there will be little selection pressure to avoid this non-host snail.     

Host cell invasion by malaria parasites

The complex life cycle of the malaria parasite includes three specialized invasive stages, distinct both in terms of their cellular architecture and in their choice of target host cell. Despite the dissimilarities between these forms, there are clear parallels in the manner by which they enter their respective host cells. Advances in the area of erythrocyte invasion by the malaria merozoite, outlined here by Chetan Chitnis and Mike Blackman and discussed at the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000, will undoubtedly impact on our understanding of mechanisms of cell entry by the other invasive forms. Similarly, recent progress in dissecting the functional role of surface proteins expressed by sporozoite and ookinete stages has provided fascinating insights into general aspects of invasion by all invasive stages of apicomplexan parasites.     

Rhadinovirus Host Entry by Co-operative Infection

Rhadinoviruses establish chronic infections of clinical and economic importance. Several show respiratory transmission and cause lung pathologies. We used Murid Herpesvirus-4 (MuHV-4) to understand how rhadinovirus lung infection might work. A primary epithelial or B cell infection often is assumed. MuHV-4 targeted instead alveolar macrophages, and their depletion reduced markedly host entry. While host entry was efficient, alveolar macrophages lacked heparan - an important rhadinovirus binding target - and were infected poorly ex vivo. In situ analysis revealed that virions bound initially not to macrophages but to heparan⁺ type 1 alveolar epithelial cells (AECs). Although epithelial cell lines endocytose MuHV-4 readily in vitro, AECs did not. Rather bound virions were acquired by macrophages; epithelial infection occurred only later. Thus, host entry was co-operative - virion binding to epithelial cells licensed macrophage infection, and this in turn licensed AEC infection. An antibody block of epithelial cell binding failed to block host entry: opsonization provided merely another route to macrophages. By contrast an antibody block of membrane fusion was effective. Therefore co-operative infection extended viral tropism beyond the normal paradigm of a target cell infected readily in vitro; and macrophage involvement in host entry required neutralization to act down-stream of cell binding.     

Host identification by Schistosoma japonicum cercariae

Attachment, the first phase of host identification by Schistosoma japonicum cercariae, can occur in 2 different ways. Cercariae clinging to the water surface simply swing around and transfer to the host skin. Free-swimming cercariae behave like S. mansoni: upon touching a substrate, they switch from tailward to forward movement, swim in an arc, and attach to it with the penetration organ. Neither type of attachment is influenced by chemical, thermal, or specific mechanical stimuli from the host. The second phase, remaining on the host, requires a solid hydrophobic surface and seems to depend only on the cercaria's ability to cling to it. This phase is not influenced by chemical or thermal stimuli. The third phase, creeping across the host surface, is independent of chemical and mechanical stimuli. Cercariae migrate in thermal gradients to a preferred temperature of 37 +/- 3 C and then attempt to penetrate. Penetration, the fourth phase, was evoked by human skin surface lipids. The free fatty acid (FA) fraction was identified as exclusively stimulating components. Saturated FA's were effective at chain lengths between 10 and 14 carbon atoms (pH 7.0), and unsaturated FA's were effective at longer chains and their activity increased with increasing number of double bonds. Dog skin surface components did not stimulate cercarial penetration, which can be attributed to the lack of free FA's. A temperature of 32-40 C also stimulated penetration responses, which might be the main stimulus in animal hosts, whose skin surfaces contain no or only a few free FA's. FA's and heat evoked a transformation of cercarial tegument simultaneous with penetration behavior, making the organisms osmotically sensitive. The host identification of S. japonicum cercariae is very nonspecific compared with the differentiated host recognition of S. mansoni.     

Temporal and Anatomical Host Resistance to Chronic Salmonella Infection Is Quantitatively Dictated by Nramp1 and Influenced by Host Genetic Background

The lysosomal membrane transporter, Nramp1, plays a key role in innate immunity and resistance to infection with intracellular pathogens such as non-typhoidal Salmonella (NTS). NTS-susceptible C57BL/6 (B6) mice, which express the mutant Nramp1^D169 allele, are unable to control acute infection with Salmonella enterica serovar Typhimurium following intraperitoneal or oral inoculation. Introducing functional Nramp1^G169 into the B6 host background, either by constructing a congenic strain carrying Nramp1^G169 from resistant A/J mice (Nramp-Cg) or overexpressing Nramp1^G169 from a transgene (Nramp-Tg), conferred equivalent protection against acute Salmonella infection. In contrast, the contributions of Nramp1 for controlling chronic infection are more complex, involving temporal and anatomical differences in Nramp1-dependent host responses. Nramp-Cg, Nramp-Tg and NTS-resistant 129×1/SvJ mice survived oral Salmonella infection equally well for the first 2–3 weeks, providing evidence that Nramp1 contributes to the initial control of NTS bacteremia preceding establishment of chronic Salmonella infection. By day 30, increased host Nramp1 expression (Tg>Cg) provided greater protection as indicated by decreased splenic bacterial colonization (Tg<Cg). However, despite controlling bacterial growth within MLN as effectively as 129×1/SvJ mice, Nramp-Cg and Nramp-Tg mice eventually succumbed to infection. These data indicate: 1) discrete, anatomically localized host resistance is conferred by Nramp1 expression in NTS-susceptible mice, 2) restriction of systemic bacterial growth in the spleens of NTS-susceptible mice is enhanced by Nramp1 expression and dose-dependent, and 3) host genes other than Nramp1 also contribute to the ability of NTS-resistant 129×1/SvJ mice to control bacterial replication during chronic infection.     

Regulation of Progeny Sex by Anisopteromalus calandrae (Hymenoptera: Pteromalidae) in Relation to Host Preference,Host Vulnerability and Host Size

Regulation of progeny sex by Anisopteromalus calandrae (Howard) in relation to host preference, host vulnerability and host size was studied with two host species, Sitophilus oryzae (L.) and Callosobruchus chinensis L. A. calandrae preferred S. oryzae to C. chinensis (preference index = 0.87). The progeny sex ratio (females/total) was significantly higher on C. chinensis, the less preferred host, than on S. oryzae regardless of the instar age of the two host species. A. calandrae could locate only a few young larvae of C. chinensis (≤third instar), which could be apparently due to the low vulnerability of the young larvae locating deeper in the adzuki bean kernels. The larval instar age of Sitophilus oryzae affect the progeny sex ratio of A. calandrae, but that of Callosobruchus chinensis did not except invulnerable ones. The progeny sex ratio of A. calandrae produced from C. chinensis, ranged from 0.66±0.05 to 0.82±0.02. The invulnerability of the young larval instar of C. chinensis and regulation of the progeny sex ratio by A. calandrae based on host size in a manner of absolute rule could explain the higher sex ratio on the young larval instar of C. chinensis, less preferred and less vulnerable host, than the old larval instar of S. oryzae, highly preferred host. The differences in host vulnerability could be another factor for A. calandrae assigning progeny sex ratio.     

Target Host Finding by Steinernema feltiae and Heterorhabditis bacteriophora in the Presence of a Non-Target Insect Host

The ability of Steinernema feltiae or Heterorhabditis bacteriophora infective juveniles (IJ), when applied to the soil surface, to infect a Galleria mellonella larva at the base of a soil-filled cup (276 cm³) was evaluated in the presence and absence of 100 larvae of a non-target insect, the aphid midge Aphidoletes aphidimyza, near the soil surface. In all four trials with either S. feltiae or H. bacteriophora, A. aphidimyza presence did not affect the number of IJ finding and infecting a G. mellonella larva. Steinernema feltiae and H. bacteriophora IJ movement (as measured by the percentage of IJ aggregating on either side of an experimental arena) in the presence of one or many A. aphidimyza larvae was evaluated in agar- and soil-filled petri dishes, respectively. Infective juvenile movement in the presence of A. aphidimyza did not differ from random, indicating that IJ were not attracted to A. aphidimyza. It is suggested, therefore, that A. aphidimyza does not reduce IJ efficacy when these two forms of biological control agent are present together in a field situation even though it is known that A. aphidimyza is susceptible to IJ of these species.     

An Endoparasitoid Avoids Hyperparasitism by Manipulating Immobile Host Herbivore to Modify Host Plant Morphology

Many parasitic organisms have an ability to manipulate their hosts to increase their own fitness. In parasitoids, behavioral changes of mobile hosts to avoid or protect against predation and hyperparasitism have been intensively studied, but host manipulation by parasitoids associated with endophytic or immobile hosts has seldom been investigated. We examined the interactions between a gall inducer Masakimyia pustulae (Diptera: Cecidomyiidae) and its parasitoids. This gall midge induces dimorphic leaf galls, thick and thin types, on Euonymus japonicus (Celastraceae). Platygaster sp. was the most common primary parasitoid of M. pustulae. In galls attacked by Platygaster sp., whole gall thickness as well as thicknesses of upper and lower gall wall was significantly larger than unparasitized galls, regardless of the gall types, in many localities. In addition, localities and tree individuals significantly affected the thickness of gall. Galls attacked by Platygaster sp. were seldom hyperparasitized in the two gall types. These results strongly suggest that Platygaster sp. manipulates the host plant''s development to avoid hyperparasitism by thickening galls.     

Host cellular signaling induced by influenza virus

A wide range of host cellular signal transduction pathways can be stimulated by influenza virus infection. Some of these signal transduction pathways induce the host cell’s innate immune response against influenza virus, while others are essential for efficient influenza virus replication. This review examines the cellular signaling induced by influenza virus infection in host cells, including host pattern recognition receptor (PRR)-related signaling, protein kinase C (PKC), Raf/MEK/ERK and phosphatidylinositol- 3-kinase (PI3K)/Akt signaling, and the corresponding effects on the host cell and/or virus, such as recognition of virus by the host cell, viral absorption and entry, viral ribonucleoprotein (vRNP) export, translation control of cellular and viral proteins, and virus-induced cell apoptosis. Research into influenza virus-induced cell signaling promotes a clearer understanding of influenza virus-host interactions and assists in the identification of novel antiviral targets and antiviral strategies.     

Host detection by four Australian tick species

The behavior of 4 tick species in the presence of their dominant host species was examined. Nymphs and adult ticks could locate a host from greater distances than the larvae. Adult Aponomma concolor were able to locate their mammalian host (echidna) from distances greater than 3 reptile-infesting species could locate their hosts. The results suggested that all 4 tick species detect hosts passively, which may be related to the relative scarcity of hosts and their irregular use of refuge sites.     

Host castration by Aphidius ervi venom proteins

The braconid Aphidius ervi Haliday (Hymenoptera, Braconidae) is an endophagous parasitoid of the pea aphid, Acyrthosiphon pisum (Harris) (Homoptera, Aphididae). Parasitized host aphids show different degrees of castration, a response that is total when parasitoid oviposition takes place in first instar hosts. Deleterious effects on the host reproductive system are already evident by 24h following parasitization, before egg hatching. The effect of parasitoid venom on A. pisum ovaries has been studied by performing microinjections in non-parasitized host aphids and observing the cellular alterations of the apical germaria of ovarioles. Venom injection reproduced the same alterations observed in parasitized aphids, while injections of saline solution did not induce any detectable change. By 24h, the germarial cells of both venom-treated aphids and parasitized aphids showed the absence of the nucleolus and of electron-dense material around the nucleus, frequently referred to as "nuage material". By 48h more evident signs of degeneration were observed, suggesting the possible occurrence of apoptosis. The bioactive component of the venom was both heat- and protease-sensitive. The activity was found in purified fractions that were highly enriched in two proteins with an approximate molecular mass of 21kD and 36kD, respectively. These macromolecules are the most abundant components of A. ervi venom and, unlike many venom proteins of studied parasitic Hymenoptera, are not glycosylated and appear to be subunits of an oligomeric protein. The adaptive significance of host castration is discussed.     

Host plant specialization driven by sexual selection

We propose a new mechanism based on sexual selection to explain the evolution of diet breadth in insects. More specifically, we show that mate choice in females for certain diet-derived male pheromones can be exploited by maternal effect genes that preferentially place offspring on a specific host plant, resulting in specialization. Our analytical model also suggests that the process is more likely to occur with species that show male-congregating mating strategies, such as lekking and hilltopping. The model offers a new explanation for the similarity between the composition of male lepidopteran pheromones and the chemistry of their host plants and also suggests a novel mechanism of host plant shift. This is the first time that sexual selection has been proposed to drive host plant specialization and the first time that a mechanism with selection acting solely on the adult stage has been shown to be capable of determining larval feeding habits.