Host Mimicry Research Articles

Zenopontonia soror caridean shrimp exhibits dynamical mimicry with sea star host switching

Zenopontonia soror (Nobili, 1904) (Caridea: Palaemonidae) is a shrimp symbiont of several sea star species that exhibits homochromy with distinct mimetic coloration according to host species. To date, populations of Z. soror have been studied extensively in the Indo-Pacific and Gulf of Panama; however, those present in the Gulf of California (Mexico) have not been evaluated. Here we conduct the first evaluation of the diversity of chromotypes present in Z. soror populations in Bahía de La Paz (Baja California Sur, Mexico), and experimentally tested how long shrimp take to archieve mimicry post sea star switch. We hypothesized that Z. soror individuals rapidly change coloration (minutes to few hours) throughout their ontogeny to mimic the coloration of host species to decrease risk of predation. This hypothesis was tested by translocating Z. soror individuals to a different sea star species with different coloration and background in the field and under laboratory conditions for three consecutive days. At least 18 chromotypes of Z. soror were identified among 386 observed specimens based on the RGB color system; and colors were independent of body size. Each chromotype holds different relative abundance in the population. Coloration was not distinctive of each individual, while color intensity increased along ontogeny development from semi-transparent (juveniles) to solid coloration (adult phase). Dynamic contraction or dispersion of the chromatophores (pigment migration) caused changes in coloration to resemble coloration of the basibiont sea star. Full mimicry of new host was achieved within 36 h in field and laboratory conditions. Zenopontonia soror individuals were observed to mimic the white spines of the sea star host Acanthaster solaris by exhibiting a white dorsal band, while others selected color-concealing hosts to stay cryptic for a short time. We conclude that Z. soror dynamically shifts coloration as an adaptation to match the symbiont shrimp–sea star host coloration to minimize or prevent predation, but individuals are vulnerable to be detected by visual predators during the color transition (<36 h period). The combined use of the Hogben and Slome index and the RGB color system from digital images provide the most precise method to assign intensity and color in epibiont-host organisms to understand the complex process of homochromy.

Analysis of Bacterial Phosphorylcholine-Related Genes Reveals an Association between Type-Specific Biosynthesis Pathways and Biomolecules Targeted for Phosphorylcholine Modification.

Many bacterial surface proteins and carbohydrates are modified with phosphorylcholine (ChoP), which contributes to host mimicry and can also promote colonization and survival in the host. However, the ChoP biosynthetic pathways that are used in bacterial species that express ChoP have not been systematically studied. For example, the well-studied Lic-1 pathway is absent in some ChoP-expressing bacteria, such as Neisseria meningitidis and Neisseria gonorrhoeae. This raises a question as to the origin of the ChoP used for macromolecule biosynthesis in these species. In the current study, we used in silico analyses to identify the potential pathways involved in ChoP biosynthesis in genomes of the 26 bacterial species reported to express a ChoP-modified biomolecule. We used the four known ChoP biosynthetic pathways and a ChoP transferase as search terms to probe for their presence in these genomes. We found that the Lic-1 pathway is primarily associated with organisms producing ChoP-modified carbohydrates, such as lipooligosaccharide. Pilin phosphorylcholine transferase A (PptA) homologs were detected in all bacteria that express ChoP-modified proteins. Additionally, ChoP biosynthesis pathways, such as phospholipid N-methyltransferase (PmtA), phosphatidylcholine synthase (Pcs), or the acylation-dependent phosphatidylcholine biosynthesis pathway, which generate phosphatidylcholine, were also identified in species that produce ChoP-modified proteins. Thus, a major finding of this study is the association of a particular ChoP biosynthetic pathway with a cognate, target ChoP-modified surface factor; i.e., protein versus carbohydrate. This survey failed to identify a known biosynthetic pathway for some species that express ChoP, indicating that a novel ChoP biosynthetic pathway(s) may remain to be identified. IMPORTANCE The modification of bacterial surface virulence factors with phosphorylcholine (ChoP) plays an important role in bacterial virulence and pathogenesis. However, the ChoP biosynthetic pathways in bacteria have not been fully understood. In this study, we used in silico analysis to identify potential ChoP biosynthetic pathways in bacteria that express ChoP-modified biomolecules and found the association between a specific ChoP biosynthesis pathway and the cognate target ChoP-modified surface factor.

Unveiling the Secretome of the Fungal Plant Pathogen Neofusicoccum parvum Induced by In Vitro Host Mimicry

Neofusicoccum parvum is a fungal plant pathogen of a wide range of hosts but knowledge about the virulence factors of N. parvum and host–pathogen interactions is rather limited. The molecules involved in the interaction between N. parvum and Eucalyptus are mostly unknown, so we used a multi-omics approach to understand pathogen–host interactions. We present the first comprehensive characterization of the in vitro secretome of N. parvum and a prediction of protein–protein interactions using a dry-lab non-targeted interactomics strategy. We used LC-MS to identify N. parvum protein profiles, resulting in the identification of over 400 proteins, from which 117 had a different abundance in the presence of the Eucalyptus stem. Most of the more abundant proteins under host mimicry are involved in plant cell wall degradation (targeting pectin and hemicellulose) consistent with pathogen growth on a plant host. Other proteins identified are involved in adhesion to host tissues, penetration, pathogenesis, or reactive oxygen species generation, involving ribonuclease/ribotoxin domains, putative ricin B lectins, and necrosis elicitors. The overexpression of chitosan synthesis proteins during interaction with the Eucalyptus stem reinforces the hypothesis of an infection strategy involving pathogen masking to avoid host defenses. Neofusicoccum parvum has the molecular apparatus to colonize the host but also actively feed on its living cells and induce necrosis suggesting that this species has a hemibiotrophic lifestyle.

Investigating the disordered regions (MoRFs, SLiMs and LCRs) and functions of mimicry proteins/peptides in silico

Microbial mimicry of the host proteins/peptides can elicit host auto-reactive T- or B-cells resulting in autoimmune disease(s). Since intrinsically disordered protein regions (IDPRs) are involved in several host cell signaling and PPI networks, molecular mimicry of the IDPRs can help the pathogens in substituting their own proteins in the host cell-signaling and PPI networks and, ultimately hijacking the host cellular machinery. Thus, the present study was conducted to discern the structural disorder and intrinsically disordered protein regions (IDPRs) like, molecular recognition features (MoRFs), short linear motifs (SLiMs), and low complexity regions (LCRs) in the experimentally verified mimicry proteins and peptides (mimitopes) of bacteria, viruses and host. Also, functional characteristics of the mimicry proteins were studied in silico. Our results indicated that 78% of the bacterial host mimicry proteins and 45% of the bacterial host mimitopes were moderately/highly disordered while, 73% of the viral host mimicry proteins and 31% of the viral host mimitopes were moderately/highly disordered. Among the pathogens, 27% of the bacterial mimicry proteins and 13% of the bacterial mimitopes were moderately/highly disordered while, 53% of the viral mimicry proteins and 21% of the viral mimitopes were moderately/highly disordered. Though IDPR were frequent in host, bacterial and viral mimicry proteins, only a few mimitopes overlapped with the IDPRs like, MoRFs, SLiMs and LCRs. This suggests that most of the microbes cannot use molecular mimicry to modulate the host PPIs and hijack the host cell machinery. Functional analyses indicated that most of the pathogens exhibited mimicry with the host proteins involved in ion binding and signaling pathways. This is the first report on the disordered regions and functional aspects of experimentally proven host and microbial mimicry proteins.

Network analysis of host-pathogen protein interactions in microbe induced cardiovascular diseases

Large-scale visualization and analysis of HPIs involved in microbial CVDs can provide crucial insights into the mechanisms of pathogenicity. The comparison of CVD associated HPIs with the entire set of HPIs can identify the pathways specific to CVDs. Therefore, topological properties of HPI networks in CVDs and all pathogens was studied using Cytoscape3.5.1. Ontology and pathway analysis were done using KOBAS 3.0. HPIs of Papilloma, Herpes, Influenza A virus as well as Yersinia pestis and Bacillus anthracis among bacteria were predominant in the whole (wHPI) and the CVD specific (cHPI) network. The central viral and secretory bacterial proteins were predicted virulent. The central viral proteins had higher number of interactions with host proteins in comparison with bacteria. Major fraction of central and essential host proteins interacts with central viral proteins. Alpha-synuclein, Ubiquitin ribosomal proteins, TATA-box-binding protein, and Polyubiquitin-C &B proteins were the top interacting proteins specific to CVDs. Signaling by NGF, Fc epsilon receptor, EGFR and ubiquitin mediated proteolysis were among the top enriched CVD specific pathways. DEXDc and HELICc were enriched host mimicry domains that may help in hijacking of cellular machinery by pathogens. This study provides a system level understanding of cardiac damage in microbe induced CVDs.

Biosynthesis of UDP-2-acetamido-4-formamido-2,4,6-trideoxy-hexose by WekG, WekE, WekF, and WekD: Enzymes in the Wek pathway responsible for O-antigen Assembly in Escherichia coli O119

Considering the importance of bacterial glycoconjugates on virulence and host mimicry, there is a need to better understand the biosynthetic pathways of these unusual sugars to identify critical targets involved in bacterial pathogenesis. In this report, we describe the cloning, overexpression, purification, and biochemical characterization of the four central enzymes in the biosynthesis pathway for UDP-2-acetamido-4-formamido-2,4,6-trideoxy-hexose, WekG, WekE, WekF, and WekD. Product peaks from enzyme-substrate reactions were detected by using a combination of capillary electrophoresis (CE) and electrospray ionization-mass spectrometry (ESI-MS). Putative enzyme assignments were provided by protein sequence analysis. Combined with the mass spectrometric characterization of pathway intermediates, we propose a biosynthetic pathway for UDP-2-acetamido-4-formamido-2,4,6-trideoxy-hexose. This process involves C-4, C-6 dehydration, C-4 amination, and formylation. CID-ESI-MSn result confirmed that the final product is a 4 formamido derivative too rather than the 3 formamido derivatives as reported earlier.

Diverse viral proteases activate the NLRP1 inflammasome

The NLRP1 inflammasome is a multiprotein complex that is a potent activator of inflammation. Mouse NLRP1B can be activated through proteolytic cleavage by the bacterial Lethal Toxin (LeTx) protease, resulting in degradation of the N-terminal domains of NLRP1B and liberation of the bioactive C-terminal domain, which includes the caspase activation and recruitment domain (CARD). However, natural pathogen-derived effectors that can activate human NLRP1 have remained unknown. Here, we use an evolutionary model to identify several proteases from diverse picornaviruses that cleave human NLRP1 within a rapidly evolving region of the protein, leading to host-specific and virus-specific activation of the NLRP1 inflammasome. Our work demonstrates that NLRP1 acts as a 'tripwire' to recognize the enzymatic function of a wide range of viral proteases and suggests that host mimicry of viral polyprotein cleavage sites can be an evolutionary strategy to activate a robust inflammatory immune response.

Hiding in plain sight: experimental evidence for birds as selective agents for host mimicry in mistletoes

Many Australian mistletoe species are cryptic, closely resembling their host foliage and overall appearance. Seed-dispersing birds have been proposed as a selective agent for host resemblance, with cryptic mistletoes only located by thoroughly searching through canopies regardless of infection status, boosting mistletoe populations by increasing the frequency of seeds dispersed to uninfected hosts; however, this idea is as yet untested. We measured bird visitation to fruiting mistletoes (n = 20) over two consecutive days, with manual defoliation of the mistletoe occurring before observation began on the second day to determine the effect of the visual appearance of the mistletoe on potential seed-dispersing birds, expecting defoliation to reduce the number of visits. Visits to the mistletoes were compared between days of observation and dietary guild (mistletoe specialist/nonspecialist). Intact mistletoes were visited more than the defoliated mistletoes, and the dietary guilds differed in their visitation patterns. This work demonstrates that the visual acuity of seed-dispersers can distinguish subtle differences in mistletoe phenotypes within infected hosts, consistent with the hypothesis that those mistletoes that more closely resemble their hosts are more difficult to perceive from afar and therefore more likely to have their seeds dispersed to uninfected hosts.

Molecular host mimicry and manipulation in bacterial symbionts.

It is common among intracellular bacterial pathogens to use eukaryotic-like proteins that mimic and manipulate host cellular processes to promote colonization and intracellular survival. Eukaryotic-like proteins are bacterial proteins with domains that are rare in bacteria, and known to function in the context of a eukaryotic cell. Such proteins can originate through horizontal gene transfer from eukaryotes or, in the case of simple repeat proteins, through convergent evolution. Recent studies of microbiomes associated with several eukaryotic hosts suggest that similar molecular strategies are deployed by cooperative bacteria that interact closely with eukaryotic cells. Some mimics, like ankyrin repeats, leucine rich repeats and tetratricopeptide repeats are shared across diverse symbiotic systems ranging from amoebae to plants, and may have originated early, or evolved independently in multiple systems. Others, like plant-mimicking domains in members of the plant microbiome are likely to be more recent innovations resulting from horizontal gene transfer from the host, or from microbial eukaryotes occupying the same host. Host protein mimics have only been described in a limited set of symbiotic systems, but are likely to be more widespread. Systematic searches for eukaryote-like proteins in symbiont genomes could lead to the discovery of novel mechanisms underlying host-symbiont interactions.

Cryptic speciation yields remarkable mimics: A new genus of sea slugs that masquerade as toxic algae (Caulerpa spp.)

Abstract“Cryptic” can refer to species that match their background through camouflage or disruptive colouration, or in taxonomy to externally similar but unrecognized congeners. In adaptive resemblance, organisms resemble parts of a larger host animal or plant on which the mimic is highly cryptic. Mimetic lineages that radiate onto superficially similar hosts may contain cryptic species in both senses: taxa that are difficult to detect, and challenging for taxonomists to distinguish. Here, we describe a new genus and four species of herbivorous sea slugs (Gastropoda, Heterobranchia, Sacoglossa), including remarkable mimics of toxic green algae (Caulerpa spp.) on which the slugs feed. The long‐recognized Stiliger smaragdinus Baba 1949 is highly mimetic of “sea grapes” (Caulerpa racemosa‐lentillifera), but phylogenetic analyses of four genes indicated Stiliger was polyphyletic: the name‐bearing species grouped within Placida, whereas Caulerpa‐mimetic lineages were phylogenetically distinct. We erect the genus Sacoproteus gen. n. for S. smaragdinus (Baba 1949), and describe four new species: S. nishae sp. n. from the Indo‐Pacific, which mimics Caulerpa chemnitzia; Sacoproteus yhiae sp. n. and Sacoproteus browni sp. n. from southern Australia, which mimic Caulerpa cactoides and Caulerpa gemminata; and Sacoproteus thomasleei sp. n., a non‐mimetic west Pacific species that shared key features. Stiliger s.s. and Placida species show crypsis and aposematism but not host mimicry, although Stiliger spp. feeding on undefended algae may be Batesian mimics. Investigating the ecology and biogeography of Sacoproteus gen. n. will yield insight into how selection generates such extraordinary examples of adaptive resemblance in the marine realm.

Phosphorylcholine is located in Aggregatibacter actinomycetemcomitans fimbrial protein Flp 1

Phosphorylcholine (ChoP) is covalently incorporated into bacterial surface structures, contributing to host mimicry and promoting adhesion to surfaces. Our aims were to determine the frequency of ChoP display among Aggregatibacter actinomycetemcomitans strains, to clarify which surface structures bear ChoP, and whether ChoP-positivity relates to serum killing. The tested oral (N = 67) and blood isolates (N = 27) represented 6 serotypes. Mab TEPC-15 was used for immunoblotting of cell lysates and fractions and for immunofluorescence microscopy of cell surface-bound ChoP. The lysates were denatured with urea for hidden ChoP or treated with proteinase K to test whether it binds to a protein. Three ChoP-positive and two ChoP-negative strains were subjected to serum killing in the presence/absence of CRP and using Ig-depleted serum as complement source. Cell lysates and the first soluble cellular fraction revealed a < 10 kDa band in immunoblots. Among 94 strains, 27 were ChoP positive. No difference was found in the prevalence of ChoP-positive oral (21/67) and blood (6/27) strains. Immunofluorescence microscopy corresponded to the immunoblot results. Proteinase K abolished ChoP reactivity, whereas urea did not change the negative result. The TEPC-15-reactive protein was undetectable in Δflp1 mutant strain. The survival rate of serotype-b strains in serum was 100% irrespective of ChoP, but that of serotype-a was higher in ChoP-positive (85%) than ChoP-negative (71%) strains. The results suggest that a third of rough-colony strains harbor ChoP and that ChoP is attached to fimbrial subunit protein Flp1. It further seems that ChoP-positivity does not enhance but may reduce A. actinomycetemcomitans susceptibility to serum killing.

Insights from the redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains.

H. pylori is a Gram-negative extracellular bacterium, first discovered by the Australian physicians Barry Marshall and Robin Warren in 1982, that colonises the human stomach mucosa. It is the leading cause of peptic ulcer and commonly infects humans worldwide with prevalence as high as 90% in some countries. H. pylori infection usually results in asymptomatic chronic gastritis, however 10-15% of cases develop duodenal or gastric ulcers and 1-3% develop stomach cancer. Infection is generally acquired during childhood and persists for life in the absence of antibiotic treatment. H. pylori has had a long period of co-evolution with humans, going back to human migration out of Africa. This prolonged relationship is likely to have shaped the overall host-pathogen interactions and repertoire of virulence strategies which H. pylori employs to establish robust colonisation, escape immune responses and persist in the gastric niche. In this regard, H. pylori lipopolysaccharide (LPS) is a key surface determinant in establishing colonisation and persistence via host mimicry and resistance to cationic antimicrobial peptides. Thus, elucidation of the H. pylori LPS structure and corresponding biosynthetic pathway represents an important step towards better understanding of H. pylori pathogenesis and the development of novel therapeutic interventions.

The redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains.

Helicobacter pylori lipopolysaccharide promotes chronic gastric colonisation through O-antigen host mimicry and resistance to mucosal antimicrobial peptides mediated primarily by modifications of the lipid A. The structural organisation of the core and O-antigen domains of H. pylori lipopolysaccharide remains unclear, as the O-antigen attachment site has still to be identified experimentally. Here, structural investigations of lipopolysaccharides purified from two wild-type strains and the O-antigen ligase mutant revealed that the H. pylori core-oligosaccharide domain is a short conserved hexasaccharide (Glc-Gal-DD-Hep-LD-Hep-LD-Hep-KDO) decorated with the O-antigen domain encompassing a conserved trisaccharide (-DD-Hep-Fuc-GlcNAc-) and variable glucan, heptan and Lewis antigens. Furthermore, the putative heptosyltransferase HP1284 was found to be required for the transfer of the third heptose residue to the core-oligosaccharide. Interestingly, mutation of HP1284 did not affect the ligation of the O-antigen and resulted in the attachment of the O-antigen onto an incomplete core-oligosaccharide missing the third heptose and the adjoining Glc-Gal residues. Mutants deficient in either HP1284 or O-antigen ligase displayed a moderate increase in susceptibility to polymyxin B but were unable to colonise the mouse gastric mucosa. Finally, mapping mutagenesis and colonisation data of previous studies onto the redefined organisation of H. pylori lipopolysaccharide revealed that only the conserved motifs were essential for colonisation. In conclusion, H. pylori lipopolysaccharide is missing the canonical inner and outer core organisation. Instead it displays a short core and a longer O-antigen encompassing residues previously assigned as the outer core domain. The redefinition of H. pylori lipopolysaccharide domains warrants future studies to dissect the role of each domain in host-pathogen interactions. Also enzymes involved in the assembly of the conserved core structure, such as HP1284, could be attractive targets for the design of new therapeutic agents for managing persistent H. pylori infection causing peptic ulcers and gastric cancer.

How Tolerance Shapes the Development of the HIV-1 Broadly Neutralizing Antibody 2F5

Abstract An effective HIV-1 vaccine is likely to require induction of broadly neutralizing antibodies (bnAbs), which neutralize multiple HIV-1 strains. Generating HIV-1 bnAbs has been challenging due partly to a number of viral immune evasion mechanisms, including viral molecular mimicry of host in order to exploit immunological tolerance. Indeed, generation of neutralizing antibodies to the 2F5 epitope of HIV-1 gp41 is proscribed by immune tolerance. However, the specific mechanisms by which tolerance relieves the autoreactivity of B cells expressing the VH and VL regions (dKI) or the VH region (sKI) of the 2F5 bnAb are not well understood. To compare the reactivity and repertoire of 2F5 dKI and sKI B cells before and after immune tolerance checkpoints, we used a newly developed in vitro single B cell culture system that induces B cell expansion and differentiation into Ab-secreting plasmacytes. The reactivities of expanded B cell clones were determined by ELISA, while repertoire was determined by recovering the V(D)J rearrangements using RT-PCR and Sanger sequencing. In 2F5 dKI mice, the great majority of cells in the small-pre-B compartment express the knock in heavy- and light-chains, and maintain HIV-1 gp41-reactivity. However, 2F5 dKI B cells that survive tolerance checkpoints to become mature B cells have undergone extensive light-chain editing and are purged of gp41- and KYNU-reactivity. Importantly, the peripheral 2F5 dKI IgM−IgD+ (anergic) B cell subset retains a substantial fraction of HIV-1- and KYNU-reactive cells. In conclusion, our study provides mechanistic insights into how immunological tolerance impairs humoral responses to HIV-1, and suggests activation of anergic B cells as a potential target for HIV-1 vaccination.

Lipopolysaccharide Structure and Biosynthesis in Helicobacter pylori.

This review covers the current knowledge and gaps in Helicobacter pylori lipopolysaccharide (LPS) structure and biosynthesis. H. pylori is a Gram-negative bacterium which colonizes the luminal surface of the human gastric epithelium. Both a constitutive alteration of the lipid A preventing TLR4 elicitation and host mimicry of the Lewis antigen decorated O-antigen of H. pylori LPS promote immune escape and chronic infection. To date, the complete structure of H. pylori LPS is not available, and the proposed model is a linear arrangement composed of the inner core defined as the hexa-saccharide (Kdo-LD-Hep-LD-Hep-DD-Hep-Gal-Glc), the outer core composed of a conserved trisaccharide (-GlcNAc-Fuc-DD-Hep-) linked to the third heptose of the inner core, the glucan, the heptan and a variable O-antigen, generally consisting of a poly-LacNAc decorated with Lewis antigens. Although the glycosyltransferases (GTs) responsible for the biosynthesis of the H. pylori O-antigen chains have been identified and characterized, there are many gaps in regard to the biosynthesis of the core LPS. These limitations warrant additional mutagenesis and structural studies to obtain the complete LPS structure and corresponding biosynthetic pathway of this important gastric bacterium.

Plant immunity: Host mimicry of pathogen virulence targets.

An integrated DNA-binding domain in a plant immune receptor functions as a decoy to detect pathogen effectors that target host transcription factors.

Polyreactivity and autoreactivity among HIV-1 antibodies.

It is generally acknowledged that human broadly neutralizing antibodies (bNAbs) capable of neutralizing multiple HIV-1 clades are often polyreactive or autoreactive. Whereas polyreactivity or autoreactivity has been proposed to be crucial for neutralization breadth, no systematic, quantitative study of self-reactivity among nonneutralizing HIV-1 Abs (nNAbs) has been performed to determine whether poly- or autoreactivity in bNAbs is a consequence of chronic antigen (Ag) exposure and/or inflammation or a fundamental property of neutralization. Here, we use protein microarrays to assess binding to >9,400 human proteins and find that as a class, bNAbs are significantly more poly- and autoreactive than nNAbs. The poly- and autoreactive property is therefore not due to the infection milieu but rather is associated with neutralization. Our observations are consistent with a role of heteroligation for HIV-1 neutralization and/or structural mimicry of host Ags by conserved HIV-1 neutralization sites. Although bNAbs are more mutated than nNAbs as a group, V(D)J mutation per se does not correlate with poly- and autoreactivity. Infrequent poly- or autoreactivity among nNAbs implies that their dominance in humoral responses is due to the absence of negative control by immune regulation. Interestingly, four of nine bNAbs specific for the HIV-1 CD4 binding site (CD4bs) (VRC01, VRC02, CH106, and CH103) bind human ubiquitin ligase E3A (UBE3A), and UBE3A protein competitively inhibits gp120 binding to the VRC01 bNAb. Among these four bNAbs, avidity for UBE3A was correlated with neutralization breadth. Identification of UBE3A as a self-antigen recognized by CD4bs bNAbs offers a mechanism for the rarity of this bNAb class. Eliciting bNAbs is key for HIV-1 vaccines; most Abs elicited by HIV-1 infection or immunization, however, are strain specific or nonneutralizing, and unsuited for protection. Here, we compare the specificities of bNAbs and nNAbs to demonstrate that bNAbs are significantly more poly- and autoreactive than nNAbs. The strong association of poly- and autoreactivity with bNAbs, but not nNAbs from infected patients, indicates that the infection milieu, chronic inflammation and Ag exposure, CD4 T-cell depletion, etc., alone does not cause poly- and autoreactivity. Instead, these properties are fundamentally linked to neutralization breadth, either by the requirement for heteroligation or the consequence of host mimicry by HIV-1. Indeed, we show that human UBE3A shares an epitope(s) with HIV-1 envelope recognized by four CD4bs bNAbs. The poly- and autoreactivity of bNAbs surely contribute to the rarity of membrane-proximal external region (MPER) and CD4bs bNAbs and identify a roadblock that must be overcome to induce protective vaccines.

An experimental test of host song mimicry as a species recognition cue among male brood parasitic indigobirds (Viduaspp.)

ABSTRACT Obligate brood parasites, which typically lack reliable interactions with conspecifics early in life, acquire species recognition cues by mechanisms other than imprinting on parents and siblings. The African indigobirds (Vidua spp.) are exceptional among brood parasites in that learning and mimicry of host vocalizations play an integral role in the social behavior of the parasites. Male indigobirds have impressive vocal repertoires featuring chatter calls, host mimicry, and complex non-mimicry songs. While chatter calls are similar, sympatric indigobirds are distinguished both by their mimicry of different hosts and by unique repertoires of non-mimicry songs. A previous playback experiment showed that male indigobirds respond differentially to natural singing (i.e. playbacks including host mimicry, chatter, and complex non-mimicry) of sympatric conspecifics and heterospecifics, but the relative role of host mimicry and complex non-mimicry in species recognition remains unknown. We addressed this ...

Host-Size-Matching in a Sperm-Dependent Asexual Fish

Among vertebrates, there are approximately fifty sperm-dependent asexual species, all of which are of hybrid origin. Sperm-dependent asexual vertebrates use sperm from one, or both, of their parental species for reproduction. To address the hypothesis that selection has resulted in asexual phenotypes that resemble their host’s phenotype, I studied size, shape, and genetic variation (using six microsatellite loci) in nine populations of a sperm-dependent asexual fish, Chrosomus eos-neogaeus, in Alberta, Canada. These nine populations differed in the presence or absence of each of the two parental species: three populations coexist with C. eos, two populations coexist with C. neogaeus, and four populations coexist with both parental species. Consistent with my hypothesis, I found that C. eos-neogaeus tended to match the body size of the parental species with which they coexist, and that C. eos-neogaeus that coexist with only C. eos were genetically divergent from C. eos-neogaeus that are syntopic with only C. neogaeus. The genetic divergence among C. eos-neogaeus populations was independent of geographic distance among populations, and estimates of quantitative trait divergence among C. eos-neogaeus populations exceeded neutral expectations. These observations suggest that processes other than migration, mutation, and drift are likely shaping the diversity of C. eos-neogaeus in the lakes sampled for this study. For example, sexual selection leading to host mimicry, or natural selection leading to environmental adaptation, may explain the observed pattern of host-size matching.

One bacterial effector with two distinct catalytic activities by different strains

The causative agent of Legionnaires' disease, Legionella pneumophila , is a master manipulator of various eukaryotic hosts ranging from unicellular amoebae to mammals [1]. This intracellular pathogen, which invades macrophages in mammalian hosts, evades the default endosome–lysosome pathway and remodels the phagosome, enclosing it in an endoplasmic reticulum‐derived Legionella ‐containing vacuole (LCV). L. pneumophila facilitates this by hijacking a myriad of eukaryotic cellular functions through translocation of around 300 effectors into the host cell by the Dot/Icm type IVB secretion apparatus. More than 70 of the injected effector proteins contain eukaryotic‐like domains, including the ankyrin repeat, Sel1, F‐box, SET, U‐box and leucine‐rich repeats, which suggests L. pneumophila hijacks and manipulates various eukaryotic processes through molecular mimicry. Elegant work by Rolando et al [2] and Li et al [3] described a new effector, designated RomA or LegAS4, respectively, which exhibits molecular mimicry of host SET‐domain‐containing histone methyltransferases to hijack host transcriptional programming by methylating histones on specific lysine residues [2,3]. Histone methylation has a crucial role in epigenetic control of gene transcription. Prior to these findings, no intracellular pathogen had been shown to directly affect chromatin architecture to alter the host cell transcriptional landscape. Rolando and Li both show that RomA/LegAS4 is a histone methyltransferase, but that the functional phenotype of RomA/LegAS4 is different in the two strains of L. pneumophila used in the two studies. Rolando et al primarily used the …