scholarly journals The Vertebrate TLR Supergene Family Evolved Dynamically by Gene Gain/Loss and Positive Selection Revealing a Host–Pathogen Arms Race in Birds

Diversity ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 131 ◽  
Author(s):  
Imran Khan ◽  
Emanuel Maldonado ◽  
Liliana Silva ◽  
Daniela Almeida ◽  
Warren E. Johnson ◽  
...  
Keyword(s):  
Positive Selection ◽  
Rapid Evolution ◽  
Immune Defense ◽  
Arms Race ◽  
Gene Gain ◽  
Toll Like Receptor ◽  
Viral Pathogens ◽  
Host Pathogen ◽  
Gain Loss ◽  
Supergene Family

The vertebrate toll-like receptor (TLRs) supergene family is a first-line immune defense against viral and non-viral pathogens. Here, comparative evolutionary-genomics of 79 vertebrate species (8 mammals, 48 birds, 11 reptiles, 1 amphibian, and 11 fishes) revealed differential gain/loss of 26 TLRs, including 6 (TLR3, TLR7, TLR8, TLR14, TLR21, and TLR22) that originated early in vertebrate evolution before the diversification of Agnatha and Gnathostomata. Subsequent dynamic gene gain/loss led to lineage-specific diversification with TLR repertoires ranging from 8 subfamilies in birds to 20 in fishes. Lineage-specific loss of TLR8-9 and TLR13 in birds and gains of TLR6 and TLR10-12 in mammals and TLR19-20 and TLR23-27 in fishes. Among avian species, 5–10% of the sites were under positive selection (PS) (omega 1.5–2.5) with radical amino-acid changes likely affecting TLR structure/functionality. In non-viral TLR4 the 20 PS sites (posterior probability PP > 0.99) likely increased ability to cope with diversified ligands (e.g., lipopolysaccharide and lipoteichoic). For viral TLR7, 23 PS sites (PP > 0.99) possibly improved recognition of highly variable viral ssRNAs. Rapid evolution of the TLR supergene family reflects the host–pathogen arms race and the coevolution of ligands/receptors, which follows the premise that birds have been important vectors of zoonotic pathogens and reservoirs for viruses.

scholarly journals Comparative Genomics and Gene Pool Analysis Reveal the Decrease of Genome Diversity and Gene Number in Rice Blast Fungi by Stable Adaption with Rice

2021 ◽  
Vol 8 (1) ◽  
pp. 5
Author(s):  
Qi Wu ◽  
Yi Wang ◽  
Li-Na Liu ◽  
Kai Shi ◽  
Cheng-Yun Li
Keyword(s):  
Rice Blast ◽  
Rapid Evolution ◽  
Interaction Mechanism ◽  
Pool Analysis ◽  
Nucleotide Metabolism ◽  
Gene Gain ◽  
Conserved Genes ◽  
Genomic Scale ◽  
Gain Loss

Magnaporthe oryzae caused huge losses in rice and wheat production worldwide. Comparing to long-term co-evolution history with rice, wheat-infecting isolates were new-emerging. To reveal the genetic differences between rice and wheat blast on global genomic scale, 109 whole-genome sequences of M. oryzae from rice, wheat, and other hosts were reanalyzed in this study. We found that the rice lineage had gone through stronger selective sweep and fewer conserved genes than those of Triticum and Lolium lineages, which indicated that rice blast fungi adapted to rice by gene loss and rapid evolution of specific loci. Furthermore, 228 genes associated with host adaptation of M. oryzae were found by presence/absence variation (PAV) analyses. The functional annotation of these genes found that the fine turning of genes gain/loss involved with transport and transcription factor, thiol metabolism, and nucleotide metabolism respectively are major mechanisms for rice adaption. This result implies that genetic base of specific host plant may lead to gene gain/loss variation of pathogens, so as to enhance their adaptability to host. Further characterization of these specific loci and their roles in adaption and evaluation of the fungi may eventually lead to understanding of interaction mechanism and develop new strategies of the disease management.

scholarly journals Emerging Evidence for Pleiotropism of Eosinophils

2021 ◽  
Vol 22 (13) ◽  
pp. 7075
Author(s):  
José M. Rodrigo-Muñoz ◽  
Marta Gil-Martínez ◽  
Beatriz Sastre ◽  
Victoria del Pozo
Keyword(s):  
Gastrointestinal Tract ◽  
Immune Defense ◽  
Extracellular Dna ◽  
Regulatory Cells ◽  
Viral Pathogens ◽  
Effective Response ◽  
Surface Receptors ◽  
Gm Csf ◽  
Variable Surface ◽  
Macrophage Colony

Eosinophils are complex granulocytes with the capacity to react upon diverse stimuli due to their numerous and variable surface receptors, which allows them to respond in very different manners. Traditionally believed to be only part of parasitic and allergic/asthmatic immune responses, as scientific studies arise, the paradigm about these cells is continuously changing, adding layers of complexity to their roles in homeostasis and disease. Developing principally in the bone marrow by the action of IL-5 and granulocyte macrophage colony-stimulating factor GM-CSF, eosinophils migrate from the blood to very different organs, performing multiple functions in tissue homeostasis as in the gastrointestinal tract, thymus, uterus, mammary glands, liver, and skeletal muscle. In organs such as the lungs and gastrointestinal tract, eosinophils are able to act as immune regulatory cells and also to perform direct actions against parasites, and bacteria, where novel mechanisms of immune defense as extracellular DNA traps are key factors. Besides, eosinophils, are of importance in an effective response against viral pathogens by their nuclease enzymatic activity and have been lately described as involved in severe acute respiratory syndrome coronavirus SARS-CoV-2 immunity. The pleiotropic role of eosinophils is sustained because eosinophils can be also detrimental to human physiology, for example, in diseases like allergies, asthma, and eosinophilic esophagitis, where exosomes can be significant pathophysiologic units. These eosinophilic pathologies, require specific treatments by eosinophils control, such as new monoclonal antibodies like mepolizumab, reslizumab, and benralizumab. In this review, we describe the roles of eosinophils as effectors and regulatory cells and their involvement in pathological disorders and treatment.

scholarly journals A Single Adaptive Mutation in Sodium Taurocholate Cotransporting Polypeptide Induced by Hepadnaviruses Determines Virus Species Specificity

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Junko S. Takeuchi ◽  
Kento Fukano ◽  
Masashi Iwamoto ◽  
Senko Tsukuda ◽  
Ryosuke Suzuki ◽  
...  
Keyword(s):  
Amino Acid ◽  
Virus Infection ◽  
Positive Selection ◽  
Sodium Taurocholate ◽  
Arms Race ◽  
Adaptive Mutation ◽  
Molecular Evidence ◽  
Adaptive Mutations ◽  
Wide Range ◽  
Coevolutionary Arms Race

ABSTRACTHepatitis B virus (HBV) and its hepadnavirus relatives infect a wide range of vertebrates, from fish to human. Hepadnaviruses and their hosts have a long history of acquiring adaptive mutations. However, there are no reports providing direct molecular evidence for such a coevolutionary “arms race” between hepadnaviruses and their hosts. Here, we present evidence suggesting that the adaptive evolution of the sodium taurocholate cotransporting polypeptide (NTCP), an HBV receptor, has been influenced by virus infection. Evolutionary analysis of the NTCP-encoding genes from 20 mammals showed that most NTCP residues are highly conserved among species, exhibiting evolution under negative selection (dN/dSratio [ratio of nonsynonymous to synonymous evolutionary changes] of <1); this observation implies that the evolution of NTCP is restricted by maintaining its original protein function. However, 0.7% of NTCP amino acid residues exhibit rapid evolution under positive selection (dN/dSratio of >1). Notably, a substitution at amino acid (aa) 158, a positively selected residue, converting the human NTCP to a monkey-type sequence abrogated the capacity to support HBV infection; conversely, a substitution at this residue converting the monkey Ntcp to the human sequence was sufficient to confer HBV susceptibility. Together, these observations suggested a close association of the aa 158 positive selection with the pressure by virus infection. Moreover, the aa 158 sequence determined attachment of the HBV envelope protein to the host cell, demonstrating the mechanism whereby HBV infection would create positive selection at this NTCP residue. In summary, we provide the first evidence in agreement with the function of hepadnavirus as a driver for inducing adaptive mutation in host receptor.IMPORTANCEHBV and its hepadnavirus relatives infect a wide range of vertebrates, with a long infectious history (hundreds of millions of years). Such a long history generally allows adaptive mutations in hosts to escape from infection while simultaneously allowing adaptive mutations in viruses to overcome host barriers. However, there is no published molecular evidence for such a coevolutionary arms race between hepadnaviruses and hosts. In the present study, we performed coevolutionary phylogenetic analysis between hepadnaviruses and the sodium taurocholate cotransporting polypeptide (NTCP), an HBV receptor, combined with virological experimental assays for investigating the biological significance of NTCP sequence variation. Our data provide the first molecular evidence supporting that HBV-related hepadnaviruses drive adaptive evolution in the NTCP sequence, including a mechanistic explanation of how NTCP mutations determine host viral susceptibility. Our novel insights enhance our understanding of how hepadnaviruses evolved with their hosts, permitting the acquisition of strong species specificity.

scholarly journals Smc5/6-antagonism by HBx is an evolutionary-conserved function of hepatitis B virus infection in mammals

2017 ◽  
Author(s):  
Fabien Filleton ◽  
Fabien Abdul ◽  
Laetitia Gerossier ◽  
Alexia Paturel ◽  
Janet Hall ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Positive Selection ◽  
Host Species ◽  
Human Hepatocytes ◽  
Arms Race ◽  
Restriction Factor ◽  
Primary Human Hepatocytes ◽  
B Virus

AbstractInfection with Hepatitis B virus (HBV) is a major cause of liver disease and cancer in humans. HBVs (family Hepadnaviridae) have been associated with mammals for millions of years. Recently, the Smc5/6 complex, known for its essential housekeeping functions in genome maintenance, was identified as an antiviral restriction factor of human HBV. The virus has however developed a counteraction mechanism by degrading the complex via its regulatory HBx protein. Whether the antiviral activity of the Smc5/6 complex against hepadnaviruses is an important and evolutionary-conserved function is unknown. Here, we used a combined evolutionary and functional approach to address this question. We first performed phylogenetic and positive selection analyses of the six Smc5/6 complex subunits and found that they have been highly conserved in primates and mammals. Yet, the Smc6 subunit showed marks of adaptive evolution, potentially reminiscent of virus-host “arms-race” We then functionally tested the HBx from six very divergent hepadnaviruses now naturally infecting primates, rodents, and bats. Despite little sequence homology, we demonstrate that these HBx efficiently degraded mammalian Smc5/6 complexes, independently of the host species and of the sites under positive selection. Importantly, all also rescued the replication of an HBx-deficient HBV in primary human hepatocytes. These findings point to an evolutionary-conserved requirement for Smc5/6 inactivation by HBx, showing that the Smc5/6 antiviral activity has been an important defense mechanism against hepadnaviruses in mammals. Interestingly, Smc5/6 may further be a restriction factor of other yet unidentified viruses that have driven some of its adaptation.ImportanceInfection with hepatitis B virus (HBV) led to 887000 human deaths in 2015. HBV has been co-evolving with mammals for millions of years. Recently, the Smc5/6 complex, known for its essential housekeeping functions, was identified as a restriction factor of human HBV antagonized by the regulatory HBx protein. Here, we address whether the antiviral activity of Smc5/6 is an important evolutionary-conserved function. We found that all six subunits of Smc5/6 have been conserved in primates with only Smc6 showing signatures of “evolutionary arms-race” Using evolutionary-guided functional assays that include infections of primary human hepatocytes, we demonstrate that HBx from very divergent mammalian HBVs could all efficiently antagonize Smc5/6, independently of the host species and sites under positive selection. These findings show that the Smc5/6 antiviral activity against HBV is an important function in mammals. It also raises the intriguing possibility that Smc5/6 restricts other, yet unidentified viruses.

scholarly journals Cause and Effectors: Whole-Genome Comparisons Reveal Shared but Rapidly Evolving Effector Sets among Host-Specific Plant-Castrating Fungi

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
William C. Beckerson ◽  
Ricardo C. Rodríguez de la Vega ◽  
Fanny E. Hartmann ◽  
Marine Duhamel ◽  
Tatiana Giraud ◽  
...  
Keyword(s):  
Positive Selection ◽  
Plant Pathogens ◽  
Pfam Domain ◽  
Rapid Evolution ◽  
Host Specialization ◽  
Secreted Proteins ◽  
Smut Fungi ◽  
Core Proteins ◽  
Genes Encoding ◽  
Species Specific

ABSTRACT Plant pathogens utilize a portfolio of secreted effectors to successfully infect and manipulate their hosts. It is, however, still unclear whether changes in secretomes leading to host specialization involve mostly effector gene gains/losses or changes in their sequences. To test these hypotheses, we compared the secretomes of three host-specific castrating anther smut fungi (Microbotryum), two being sister species. To address within-species evolution, which might involve coevolution and local adaptation, we compared the secretomes of strains from differentiated populations. We experimentally validated a subset of signal peptides. Secretomes ranged from 321 to 445 predicted secreted proteins (SPs), including a few species-specific proteins (42 to 75), and limited copy number variation, i.e., little gene family expansion or reduction. Between 52% and 68% of the SPs did not match any Pfam domain, a percentage that reached 80% for the small secreted proteins, indicating rapid evolution. In comparison to background genes, we indeed found SPs to be more differentiated among species and strains, more often under positive selection, and highly expressed in planta; repeat-induced point mutations (RIPs) had no role in effector diversification, as SPs were not closer to transposable elements than background genes and were not more RIP affected. Our study thus identified both conserved core proteins, likely required for the pathogenic life cycle of all Microbotryum species, and proteins that were species specific or evolving under positive selection; these proteins may be involved in host specialization and/or coevolution. Most changes among closely related host-specific pathogens, however, involved rapid changes in sequences rather than gene gains/losses. IMPORTANCE Plant pathogens use molecular weapons to successfully infect their hosts, secreting a large portfolio of various proteins and enzymes. Different plant species are often parasitized by host-specific pathogens; however, it is still unclear whether the molecular basis of such host specialization involves species-specific weapons or different variants of the same weapons. We therefore compared the genes encoding secreted proteins in three plant-castrating pathogens parasitizing different host plants, producing their spores in plant anthers by replacing pollen. We validated our predictions for secretion signals for some genes and checked that our predicted secreted proteins were often highly expressed during plant infection. While we found few species-specific secreted proteins, numerous genes encoding secreted proteins showed signs of rapid evolution and of natural selection. Our study thus found that most changes among closely related host-specific pathogens involved rapid adaptive changes in shared molecular weapons rather than innovations for new weapons.

Aids-Associated Viral Infections

1999 ◽  
Vol 5 (S2) ◽  
pp. 1098-1099
Author(s):  
Sara E. Miller
Keyword(s):  
Electron Microscopy ◽  
Human Immunodeficiency Virus ◽  
Viral Infections ◽  
Immune Defense ◽  
Detection Methods ◽  
Aids Patients ◽  
Viral Pathogens ◽  
Thin Sectioning ◽  
Immunodeficiency Virus ◽  
Life Threatening

Infection with human immunodeficiency virus (HIV) eventually causes a profound decrease in the body's ability to eradicate or control infections with microorganisms, including viruses. Some infections in AIDS patients are due to common organisms which are of little significance in immunocompetent individuals. Other organisms can be harbored continuously, occasionally causing disease, but normally being suppressed after a heightened immune defense; in AIDS patients, these infections can be life-threatening. Further, practices that predispose to HIV infection also permit entry of other organisms, such as hepatitis and herpesviruses. Electron microscopy is beneficial as an adjunct to other modalities for viral detection. Methods for identifying viruses, both in fluids by negative staining and in tissues by thin sectioning, have been published. Some viral pathogens, including HIV itself, are best documented by other means.HIV has been demonstrated by EM in infected individuals, but because it destroys and makes scarce the cells for which it has an affinity, it is difficult to find them.

scholarly journals Variation in selection constraints on teleost TLRs with emphasis on their repertoire in the Walking catfish, Clarias batrachus

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Manisha Priyam ◽  
Sanjay K. Gupta ◽  
Biplab Sarkar ◽  
T. R. Sharma ◽  
A. Pattanayak
Keyword(s):  
Phylogenetic Analysis ◽  
Positive Selection ◽  
Strong Evidence ◽  
Selection Pressure ◽  
Arms Race ◽  
Clarias Batrachus ◽  
Toll Like Receptors ◽  
Specific Variation ◽  
Species Specific ◽  
High Degree

AbstractThe high degree of conservation of toll-like receptors (TLRs), and yet their subtle variations for better adaptation of species in the host–pathogen arms race make them worthy candidates for understanding evolution. We have attempted to track the trend of TLR evolution in the most diverse vertebrate group—teleosts, where Clarias batrachus was given emphasis, considering its traits for terrestrial adaptation. Eleven C. batrachus TLRs (TLR1, 2, 3, 5, 7, 8 9, 13, 22, 25, 26) were identified in this study which clustered in proximity to its Siluriformes relative orthologues in the phylogenetic analysis of 228 TLRs from 25 teleosts. Ten TLRs (TLR1, 2, 3, 5, 7, 8 9, 13, 21, 22) with at least 15 member orthologues for each alignment were processed for selection pressure and coevolutionary analysis. TLR1, 7, 8 and 9 were found to be under positive selection in the alignment-wide test. TLR1 also showed maximum episodic diversification in its clades while the teleost group Eupercaria showed the maximum divergence in their TLR repertoire. Episodic diversification was evident in C. batrachus TLR1 and 7 alignments. These results present a strong evidence of a divergent TLR repertoire in teleosts which may be contributing towards species-specific variation in TLR functions.

scholarly journals Senescence and Host–Pathogen Interactions

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1747 ◽  
Author(s):  
Daniel Humphreys ◽  
Mohamed ElGhazaly ◽  
Teresa Frisan
Keyword(s):  
Chronic Infection ◽  
Virulence Determinants ◽  
Viral Pathogens ◽  
Host Pathogen Interaction ◽  
Cycle Arrest ◽  
Age Related ◽  
Host Pathogen ◽  
Weak Points ◽  
Innate Defence

Damage to our genomes triggers cellular senescence characterised by stable cell cycle arrest and a pro-inflammatory secretome that prevents the unrestricted growth of cells with pathological potential. In this way, senescence can be considered a powerful innate defence against cancer and viral infection. However, damage accumulated during ageing increases the number of senescent cells and this contributes to the chronic inflammation and deregulation of the immune function, which increases susceptibility to infectious disease in ageing organisms. Bacterial and viral pathogens are masters of exploiting weak points to establish infection and cause devastating diseases. This review considers the emerging importance of senescence in the host–pathogen interaction: we discuss the pathogen exploitation of ageing cells and senescence as a novel hijack target of bacterial pathogens that deploys senescence-inducing toxins to promote infection. The persistent induction of senescence by pathogens, mediated directly through virulence determinants or indirectly through inflammation and chronic infection, also contributes to age-related pathologies such as cancer. This review highlights the dichotomous role of senescence in infection: an innate defence that is exploited by pathogens to cause disease.

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