Identification of sequence motifs involved in Dengue virus–host interactions

Dengue fever is a rapidly spreading mosquito-borne virus infection, which remains a serious global public health problem. As there is no specific treatment or commercial vaccine available for effective control of the disease, the attempts on developing novel control strategies are underway. Viruses utilize the surface receptor proteins of host to enter into the cells. Though various proteins were said to be receptors of Dengue virus (DENV) using Virus Overlay Protein Binding Assay, the precise interaction between DENV and host is not explored. Understanding the structural features of domain III envelope glycoprotein would help in developing efficient antiviral inhibitors. Therefore, an attempt was made to identify the sequence motifs present in domain III envelope glycoprotein of Dengue virus. Computational analysis revealed that the NGR motif is present in the domain III envelope glycoprotein of DENV-1 and DENV-3. Similarly, DENV-1, DENV-2 and DENV-4 were found to contain Yxxphi motif which is a tyrosine-based sorting signal responsible for the interaction with a mu subunit of adaptor protein complex. High-throughput virtual screening resulted in five compounds as lead molecules based on glide score, which ranges from ?4.664 to ?6.52 kcal/Mol. This computational prediction provides an additional tool for understanding the virus–host interactions and helps to identify potential targets in the host. Further, experimental evidence is warranted to confirm the virus–host interactions and also inhibitory activity of reported lead compounds.     

Proteome analysis of virus–host cell interaction: rabies virus replication in Vero cells in two different media

The use of Vero cells for rabies vaccine production was recommended from the WHO in 2005. A controlled production process is necessary to reduce the risk of contaminants in the product. One step towards this is to turn away from animal-derived components (e.g. serum, trypsin, bovine serum albumin) and face a production process in animal component-free medium. In this study, a proteomic approach was applied, using 2-D differential gel electrophoresis and mass spectrometry to compare rabies virus propagation in Vero cells under different cultivation conditions in microcarrier culture. Protein alterations were investigated for uninfected and infected Vero cells over a time span from 1 to 8 days post-infection in two different types of media (serum-free versus serum-containing media). For mock-infected cells, proteins involved in stress response, redox status, protease activity or glycolysis, and protein components in the endoplasmic reticulum were found to be differentially expressed comparing both cultivation media at all sampling points. For virus-infected cells, additionally changes in protein expression involved in general cell regulation and in calcium homeostasis were identified under both cultivation conditions. The fact that neither of these additional proteins was identified for cells during mock infection, but similar protein expression changes were found for both systems during virus propagation, indicates for a specific response of the Vero cell proteome on rabies virus infection.     

Comparative analysis of Leishmania exoproteomes: Implication for host–pathogen interactions

Leishmaniasis is a vector-borne disease caused by the protozoa Leishmania. We have analyzed and compared the sequences of three experimental exoproteomes of Leishmania promastigotes from different species to determine their specific features and to identify new candidate proteins involved in interactions of Leishmania with the host. The exoproteomes differ from the proteomes by a decrease in the average molecular weight per protein, in disordered amino acid residues and in basic proteins. The exoproteome of the visceral species is significantly enriched in sites predicted to be phosphorylated as well as in features frequently associated with molecular interactions (intrinsic disorder, number of disordered binding regions per protein, interaction and/or trafficking motifs) compared to the other species. The visceral species might thus have a larger interaction repertoire with the host than the other species. Less than 10% of the exoproteomes contain heparin-binding and RGD sequences, and ~ 30% the host targeting signal RXLXE/D/Q. These latter proteins might thus be exported inside the host cell during the intracellular stage of the infection. Furthermore we have identified nine protein families conserved in the three exoproteomes with specific combinations of Pfam domains and selected eleven proteins containing at least three interaction and/or trafficking motifs including two splicing factors, phosphomannomutase, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, the paraflagellar rod protein-1D and a putative helicase. Their role in host–Leishmania interactions warrants further investigation but the putative ATP-dependent DEAD/H RNA helicase, which contains numerous interaction motifs, a host targeting signal and two disordered regions, is a very promising candidate.     

Environment–host–parasite interactions in mass-reared insects

The mass production of insects is rapidly expanding globally, supporting multiple industrial needs. However, parasite infections in insect mass-production systems can lower productivity and can lead to devastating losses. High rearing densities and artificial environmental conditions in mass-rearing facilities affect the insect hosts as well as their parasites. Environmental conditions such as temperature, gases, light, vibration, and ionizing radiation can affect productivity in insect mass-production facilities by altering insect development and susceptibility to parasites. This review explores the recent literature on environment–host–parasite interactions with a specific focus on mass-reared insect species. Understanding these complex interactions offers opportunities to optimise environmental conditions for the prevention of infectious diseases in mass-reared insects.     

Importance of Bacteroidetes in host–microbe interactions and ecosystem functioning

Bacteroidetes are prevalent in soil ecosystems and are associated with various eukaryotic hosts, including plants, animals, and humans. The ubiquity and diversity of Bacteroidetes exemplify their impressive versatility in niche adaptation and genomic plasticity. Over the past decade, a wealth of knowledge has been obtained on the metabolic functions of clinically relevant Bacteroidetes, but much less attention has been given to Bacteroidetes living in close association with plants. To improve our understanding of the functional roles of Bacteroidetes for plants and other hosts, we review the current knowledge of their taxonomy and ecology, in particular their roles in nutrient cycling and host fitness. We highlight their environmental distribution, stress resilience, genomic diversity, and functional importance in diverse ecosystems, including, but not limited to, plant-associated microbiomes.     

The Iron age of host–microbe interactions

Microbes exert a major impact on human health and disease by either promoting or disrupting homeostasis, in the latter instance leading to the development of infectious diseases. Such disparate outcomes are driven by the ever-evolving genetic diversity of microbes and the countervailing host responses that minimize their pathogenic impact. Host defense strategies that limit microbial pathogenicity include resistance mechanisms that exert a negative impact on microbes, and disease tolerance mechanisms that sustain host homeostasis without interfering directly with microbes. While genetically distinct, these host defense strategies are functionally integrated, via mechanisms that remain incompletely defined. Here, we explore the general principles via which host adaptive responses regulating iron (Fe) metabolism impact on resistance and disease tolerance to infection.     

Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection

The integration of proteomic methods to virology has facilitated a significant breadth of biological insight into mechanisms of virus replication, antiviral host responses and viral subversion of host defenses. Throughout the course of infection, these cellular mechanisms rely heavily on the formation of temporally and spatially regulated virus–host protein–protein interactions. Reviewed here are proteomic-based approaches that have been used to characterize this dynamic virus–host interplay. Specifically discussed are the contribution of integrative mass spectrometry, antibody-based affinity purification of protein complexes, cross-linking and protein array techniques for elucidating complex networks of virus–host protein associations during infection with a diverse range of RNA and DNA viruses. The benefits and limitations of applying proteomic methods to virology are explored, and the contribution of these approaches to important biological discoveries and to inspiring new tractable avenues for the design of antiviral therapeutics is highlighted.     

Comparative mapping of host–pathogen protein–protein interactions

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Impact of external forces on cyanophage–host interactions in aquatic ecosystems

Cyanobacterial (algal) blooms have by convention been attributed to the excessive level of nutrients from pollution and runoff, which promotes the rapid growth and multiplication of cyanobacteria or algae. The cyanophage (virus) is the natural predator of cyanobacteria (the host). The aim of this review is to unveil certain pressures that disrupt cyanophage–host interactions and the formation of cyanobacterial blooms. This review focuses principally on the impact of greenhouse gases, ozone depletion, solar ultraviolet radiation (SUR) and the role of recently discovered virophages, which coexist with and in turn are the natural predator of phages. The key findings are that the increase in SUR, the mutation of cyanophages and cyanobacteria, along with changing nutrient levels, have combined with virophages to impede cyanophage–host interactions and the resultant viral infection and killing of the cyanobacterial cell, which is a necessary step in controlling cyanobacterial blooms. Consider this a ‘call to action’ for researchers interested in corrective action aimed at evolving aquatic ecosystems.     

Antarctic archaea–virus interactions: metaproteome-led analysis of invasion,evasion and adaptation

Despite knowledge that viruses are abundant in natural ecosystems, there is limited understanding of which viruses infect which hosts, and how both hosts and viruses respond to those interactions—interactions that ultimately shape community structure and dynamics. In Deep Lake, Antarctica, intergenera gene exchange occurs rampantly within the low complexity, haloarchaea-dominated community, strongly balanced by distinctions in niche adaptation which maintain sympatric speciation. By performing metaproteomics for the first time on haloarchaea, genomic variation of S-layer, archaella and other cell surface proteins was linked to mechanisms of infection evasion. CRISPR defense systems were found to be active, with haloarchaea responding to at least eight distinct types of viruses, including those infecting between genera. The role of BREX systems in defending against viruses was also examined. Although evasion and defense were evident, both hosts and viruses also may benefit from viruses carrying and expressing host genes, thereby potentially enhancing genetic variation and phenotypic differences within populations. The data point to a complex inter-play leading to a dynamic optimization of host–virus interactions. This comprehensive overview was achieved only through the integration of results from metaproteomics, genomics and metagenomics.     

Characterization of ordered aggregates of cerato-platanin and their involvement in fungus–host interactions

Background

The “cerato-platanin family” consists of fungal-secreted proteins that are involved in various stages of the host–fungus interaction and act as phytotoxins, elicitors of defense responses and allergens. Cerato-platanin (CP) is a moderately hydrophobic protein secreted and localized in the cell wall of Ceratocystis platani, the causal agent of a severe disease of Platanus. These properties make CP like the hydrophobins: these are self-assembling proteins that form a surface coating which is involved in the formation of aerial hyphae and in adherence to surfaces.

Methods

CP aggregation was monitored by ThT, circular dichroism, and AFM. The eliciting activity of CP aggregates was assayed on leaves and cells.

Results

The CP self-assembles forming amyloid-like aggregates via a nucleated growth mechanism which is joined up with a cleavage of the N-terminus. The ovoidal shape and the lack of a clear transition toward an all-β structure distinguish these aggregates from typical amyloid fibrils. Moreover, CP aggregates interact with hydrophobic surfaces and enhance the hypersensitive response of Platanus.

Conclusion and general significance

CP forms “ordered aggregates” for which the soluble prefibrillar structures are the end point of the aggregation process, and do not evolve to insoluble fibrils. An involvement in host–microbe interaction is also suggested.     

Geographical divergence in host use ability of a marine herbivore in alga–grazer interaction

When the selective environment differs geographically, local herbivore populations may diverge in their host use ability and adapt locally to exploit the sympatric host population. We tested whether populations of the marine generalist herbivore Idotea baltica have diverged in host us ability and whether they locally adapted to exploit the sympatric population of their main host species, the bladderwrack Fucus vesiculosus. We fed isopods from three local populations reciprocally with the sympatric and two allopatric populations of the host. The bladderwrack populations varied in their quality as food for isopods suggesting variation in the selective environment. The ability to exploit the main host showed considerable divergence among the isopod populations. There was no significant interaction between host and isopod origin, indicating that the patterns observed in the reciprocal feeding experiment could be explained by differences in overall suitability of the hosts and differences in overall performance of the isopod populations. Isopod population that was sympatric to a bladderwrack population with low phlorotannin content showed high performance on the algae from the sympatric but low performance on the algae from the two allopatric populations. Performance of isopods, especially in this population, decreased quickly with the increasing phlorotannin content of food algae. We therefore hypothesize that the isopods adapted to a low phlorotannin content were unable to utilize high-phlorotannin algae efficiently. Isopod populations sympatric to the high-phlorotannin bladderwrack populations may be generally better adapted to deal with phlorotannins, being thereby able to utilize a range of bladderwrack populations.     

Novel opportunities for the exploitation of host–microbiome interactions in the intestine

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Hypothiocyanite and host–microbe interactions

The pseudohypohalous acid hypothiocyanite/hypothiocyanous acid (OSCN⁻/HOSCN) has been known to play an antimicrobial role in mammalian immunity for decades. It is a potent oxidant that kills bacteria but is non-toxic to human cells. Produced from thiocyanate (SCN⁻) and hydrogen peroxide (H₂O₂) in a variety of body sites by peroxidase enzymes, HOSCN has been explored as an agent of food preservation, pathogen killing, and even improved toothpaste. However, despite the well-recognized antibacterial role HOSCN plays in host–pathogen interactions, little is known about how bacteria sense and respond to this oxidant. In this work, we will summarize what is known and unknown about HOSCN in innate immunity and recent advances in understanding the responses that both pathogenic and non-pathogenic bacteria mount against this antimicrobial agent, highlighting studies done with three model organisms, Escherichia coli, Streptococcus spp., and Pseudomonas aeruginosa.