scholarly journals Genome plasticity in Papillomaviruses andde novoemergence ofE5oncogenes

2018 ◽  
Author(s):  
Anouk Willemsen ◽  
Marta Félez-Sánchez ◽  
Ignacio G. Bravo
Keyword(s):  
Viral Infections ◽  
De Novo ◽  
Phenotypic Diversity ◽  
Common Origin ◽  
Viral Gene ◽  
Coding Region ◽  
Clinical Presentations ◽  
E5 Protein ◽  
Genetic Novelty ◽  
The Impact

AbstractThe clinical presentations of papillomavirus (PV) infections come in many different flavors. While most PVs are part of a healthy skin microbiota and are not associated to physical lesions, other PVs cause benign lesions, and only a handful of PVs are associated to malignant transformations linked to the specific activities of theE5,E6andE7oncogenes. The functions and origin ofE5remain to be elucidated. TheseE5ORFs are present in the genomes of a few polyphyletic PV lineages, located between the early and the late viral gene cassettes. We have computationally assessed whether theseE5ORFs have a common origin and whether they display the properties of a genuine gene. Our results suggest that during the evolution ofPapillomaviridae, at least four events lead to the presence of a long non-coding DNA stretch between theE2and theL2genes. In three of these events, the novel regions evolved coding capacity, becoming the extantE5ORFs. We then focused on the evolution of theE5genes inAlphaPVsinfecting humans. The sharp match between the type of E5 protein encoded inAlphaPVsand the infection phenotype (cutaneous warts, genital warts or anogenital cancers) supports the role of E5 in the differential oncogenic potential of these PVs. In our analyses, the best-supported scenario is that the five types of extant E5 proteins within theAlphaPVgenomes may not have a common ancestor. However, the chemical similarities between E5s regarding amino acid composition prevent us from confidently rejecting the model of a common origin. Our evolutionary interpretation is that an originally non-coding region entered the genome of the ancestralAlphaPVs. This genetic novelty allowed to explore novel transcription potential, triggering an adaptive radiation that yielded three main viral lineages encoding for different E5 proteins, and that display distinct infection phenotypes. Overall, our results provide an evolutionary scenario for thede novoemergence of viral genes and illustrate the impact of such genotypic novelty in the phenotypic diversity of the viral infections.

scholarly journals HLA-E⁎01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Julie Di Cristofaro ◽  
Mathieu Pelardy ◽  
Anderson Loundou ◽  
Agnès Basire ◽  
Carine Gomez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retrospective Study ◽  
Viral Infections ◽  
De Novo ◽  
Therapeutic Option ◽  
Univariate Analysis ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Hematopoietic Stem ◽  
The Impact

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E⁎01:01 and HLA-E⁎01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p=0.01). In multivariate analysis, HLA-E⁎01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E⁎01:01 status (HR: 3.563 (CI 95%, 1.016–12),p=0.047). HLA-E allele did not affect pathogen infection or the production ofde novoDSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort.

scholarly journals The Impact of Human Genetic Polymorphisms on Rotavirus Susceptibility, Epidemiology, and Vaccine Take

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 324 ◽  
Author(s):  
Sumit Sharma ◽  
Marie Hagbom ◽  
Lennart Svensson ◽  
Johan Nordgren
Keyword(s):  
Public Health ◽  
Genetic Diversity ◽  
Immune Response ◽  
Viral Infections ◽  
Phenotypic Diversity ◽  
Health Impact ◽  
Human Populations ◽  
Blood Group Antigens ◽  
Receptor Ligand ◽  
The Impact

Innate resistance to viral infections can be attributed to mutations in genes involved in the immune response, or to the receptor/ligand. A remarkable example of the latter is the recently described Mendelian trait resistance to clinically important and globally predominating genotypes of rotavirus, the most common agent of severe dehydrating gastroenteritis in children worldwide. This resistance appears to be rotavirus genotype-dependent and is mainly mediated by histo-blood group antigens (HBGAs), which function as a receptor or attachment factors on gut epithelial surfaces. HBGA synthesis is mediated by fucosyltransferases and glycosyltransferases under the genetic control of the FUT2 (secretor), FUT3 (Lewis), and ABO (H) genes on chromosome 19. Significant genotypic and phenotypic diversity of HBGA expression exists between different human populations. This genetic diversity has an effect on genotype-specific susceptibility, molecular epidemiology, and vaccine take. Here, we will discuss studies on genetic susceptibility to rotavirus infection and place them in the context of population susceptibility, rotavirus epidemiology, vaccine take, and public health impact.

scholarly journals Assessing Genome-Wide Diversity in European Hantaviruses through Sequence Capture from Natural Host Samples

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 749 ◽  
Author(s):  
Melanie Hiltbrunner ◽  
Gerald Heckel
Keyword(s):  
High Throughput Sequencing ◽  
De Novo ◽  
Phylogenetic Analyses ◽  
Common Vole ◽  
Natural Host ◽  
Sequence Information ◽  
Coding Region ◽  
Sequence Capture ◽  
Genome Wide ◽  
The Impact

Research on the ecology and evolution of viruses is often hampered by the limitation of sequence information to short parts of the genomes or single genomes derived from cultures. In this study, we use hybrid sequence capture enrichment in combination with high-throughput sequencing to provide efficient access to full genomes of European hantaviruses from rodent samples obtained in the field. We applied this methodology to Tula (TULV) and Puumala (PUUV) orthohantaviruses for which analyses from natural host samples are typically restricted to partial sequences of their tri-segmented RNA genome. We assembled a total of ten novel hantavirus genomes de novo with very high coverage (on average >99%) and sequencing depth (average >247×). A comparison with partial Sanger sequences indicated an accuracy of >99.9% for the assemblies. An analysis of two common vole (Microtus arvalis) samples infected with two TULV strains each allowed for the de novo assembly of all four TULV genomes. Combining the novel sequences with all available TULV and PUUV genomes revealed very similar patterns of sequence diversity along the genomes, except for remarkably higher diversity in the non-coding region of the S-segment in PUUV. The genomic distribution of polymorphisms in the coding sequence was similar between the species, but differed between the segments with the highest sequence divergence of 0.274 for the M-segment, 0.265 for the S-segment, and 0.248 for the L-segment (overall 0.258). Phylogenetic analyses showed the clustering of genome sequences consistent with their geographic distribution within each species. Genome-wide data yielded extremely high node support values, despite the impact of strong mutational saturation that is expected for hantavirus sequences obtained over large spatial distances. We conclude that genome sequencing based on capture enrichment protocols provides an efficient means for ecological and evolutionary investigations of hantaviruses at an unprecedented completeness and depth.

Novel Applications of Nanotechnology in Controlling HIV and HSV Infections

2020 ◽  
Vol 12 ◽  
Author(s):  
Sai Akilesh M ◽  
Ashish Wadhwani
Keyword(s):  
Drug Delivery ◽  
Viral Infections ◽  
Polymeric Nanoparticles ◽  
Volume Ratio ◽  
Fold Increase ◽  
Multi Drug Resistance ◽  
Health Crisis ◽  
Pharmaceutical Properties ◽  
Simplex Virus ◽  
The Impact

: Infectious diseases have been prevalent since many decades and viral pathogens have caused global health crisis and economic meltdown on a devastating scale. High occurrence of newer viral infections in the recent years, in spite of the progress achieved in the field of pharmaceutical sciences defines the critical need for newer and more effective antiviral therapies and diagnostics. The incidence of multi-drug resistance and adverse effects due to the prolonged use of anti-viral therapy is also a major concern. Nanotechnology offers a cutting edge platform for the development of novel compounds and formulations for biomedical applications. The unique properties of nano-based materials can be attributed to the multi-fold increase in the surface to volume ratio at the nano-scale, tunable surface properties of charge and chemical moieties. Idealistic pharmaceutical properties such as increased bioavailability and retention times, lower toxicity profiles, sustained release formulations, lower dosage forms and most importantly, targeted drug delivery can be achieved through the approach of nanotechnology. The extensively researched nano-based materials are metal and polymeric nanoparticles, dendrimers and micelles, nano-drug delivery vesicles, liposomes and lipid based nanoparticles. In this review article, the impact of nanotechnology on the treatment of Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus (HSV) viral infections during the last decade are outlined.

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5352-5361 ◽  
Author(s):  
Jih-Luh Tang ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
Chieh-Yu Liu ◽  
Wen-Chien Chou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Rate ◽  
Adult Patients ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Runx1 Mutation ◽  
Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

scholarly journals Whole-Genome Sequencing and Characterization of Buffalo Genetic Resources: Recent Advances and Future Challenges

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 904
Author(s):  
Saif ur Rehman ◽  
Faiz-ul Hassan ◽  
Xier Luo ◽  
Zhipeng Li ◽  
Qingyou Liu
Keyword(s):  
Selective Breeding ◽  
Reference Genome ◽  
De Novo ◽  
Phenotypic Diversity ◽  
Molecular Data ◽  
Genomic Diversity ◽  
Production Performance ◽  
Phylogeographic Structure ◽  
Economic Significance ◽  
And Performance

The buffalo was domesticated around 3000–6000 years ago and has substantial economic significance as a meat, dairy, and draught animal. The buffalo has remained underutilized in terms of the development of a well-annotated and assembled reference genome de novo. It is mandatory to explore the genetic architecture of a species to understand the biology that helps to manage its genetic variability, which is ultimately used for selective breeding and genomic selection. Morphological and molecular data have revealed that the swamp buffalo population has strong geographical genomic diversity with low gene flow but strong phenotypic consistency, while the river buffalo population has higher phenotypic diversity with a weak phylogeographic structure. The availability of recent high-quality reference genome and genotyping marker panels has invigorated many genome-based studies on evolutionary history, genetic diversity, functional elements, and performance traits. The increasing molecular knowledge syndicate with selective breeding should pave the way for genetic improvement in the climatic resilience, disease resistance, and production performance of water buffalo populations globally.

scholarly journals Reproduction in Trypanosomatids: Past and Present

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 471
Author(s):  
Camino Gutiérrez-Corbo ◽  
Bárbara Domínguez-Asenjo ◽  
María Martínez-Valladares ◽  
Yolanda Pérez-Pertejo ◽  
Carlos García-Estrada ◽  
...  
Keyword(s):  
Low Income ◽  
Phenotypic Diversity ◽  
Natural Populations ◽  
Genetic Exchange ◽  
Health Concern ◽  
Current Debate ◽  
Naturally Occurring ◽  
Experimental Works ◽  
Genomic Recombination ◽  
The Impact

Diseases caused by trypanosomatids (Sleeping sickness, Chagas disease, and leishmaniasis) are a serious public health concern in low-income endemic countries. These diseases are produced by single-celled parasites with a diploid genome (although aneuploidy is frequent) organized in pairs of non-condensable chromosomes. To explain the way they reproduce through the analysis of natural populations, the theory of strict clonal propagation of these microorganisms was taken as a rule at the beginning of the studies, since it partially justified their genomic stability. However, numerous experimental works provide evidence of sexual reproduction, thus explaining certain naturally occurring events that link the number of meiosis per mitosis and the frequency of mating. Recent techniques have demonstrated genetic exchange between individuals of the same species under laboratory conditions, as well as the expression of meiosis specific genes. The current debate focuses on the frequency of genomic recombination events and its impact on the natural parasite population structure. This paper reviews the results and techniques used to demonstrate the existence of sex in trypanosomatids, the inheritance of kinetoplast DNA (maxi- and minicircles), the impact of genetic exchange in these parasites, and how it can contribute to the phenotypic diversity of natural populations.

scholarly journals The L1-dependant and Pol III transcribed Alu retrotransposon, from its discovery to innate immunity

2021 ◽  
Vol 48 (3) ◽  
pp. 2775-2789
Author(s):  
Ludwig Stenz
Keyword(s):  
Human Genome ◽  
Viral Infections ◽  
De Novo ◽  
Current Knowledge ◽  
Innate Immune ◽  
De Novo Mutation ◽  
Neuronal Diversity ◽  
Alu Sequences ◽  
Pol Iii ◽  
The Brain

AbstractThe 300 bp dimeric repeats digestible by AluI were discovered in 1979. Since then, Alu were involved in the most fundamental epigenetic mechanisms, namely reprogramming, pluripotency, imprinting and mosaicism. These Alu encode a family of retrotransposons transcribed by the RNA Pol III machinery, notably when the cytosines that constitute their sequences are de-methylated. Then, Alu hijack the functions of ORF2 encoded by another transposons named L1 during reverse transcription and integration into new sites. That mechanism functions as a complex genetic parasite able to copy-paste Alu sequences. Doing that, Alu have modified even the size of the human genome, as well as of other primate genomes, during 65 million years of co-evolution. Actually, one germline retro-transposition still occurs each 20 births. Thus, Alu continue to modify our human genome nowadays and were implicated in de novo mutation causing diseases including deletions, duplications and rearrangements. Most recently, retrotransposons were found to trigger neuronal diversity by inducing mosaicism in the brain. Finally, boosted during viral infections, Alu clearly interact with the innate immune system. The purpose of that review is to give a condensed overview of all these major findings that concern the fascinating physiology of Alu from their discovery up to the current knowledge.

scholarly journals Epigenetic Changes in Host Ribosomal DNA Promoter Induced by an Asymptomatic Plant Virus Infection

Biology ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 91 ◽  
Author(s):  
Miryam Pérez-Cañamás ◽  
Elizabeth Hevia ◽  
Carmen Hernández
Keyword(s):  
Gene Silencing ◽  
Ribosomal Dna ◽  
Plant Virus ◽  
Dna Methyltransferase ◽  
Cytosine Methylation ◽  
De Novo ◽  
Methylation Pattern ◽  
Transcriptional Gene Silencing ◽  
Post Transcriptional Gene Silencing ◽  
The Impact

DNA cytosine methylation is one of the main epigenetic mechanisms in higher eukaryotes and is considered to play a key role in transcriptional gene silencing. In plants, cytosine methylation can occur in all sequence contexts (CG, CHG, and CHH), and its levels are controlled by multiple pathways, including de novo methylation, maintenance methylation, and demethylation. Modulation of DNA methylation represents a potentially robust mechanism to adjust gene expression following exposure to different stresses. However, the potential involvement of epigenetics in plant-virus interactions has been scarcely explored, especially with regard to RNA viruses. Here, we studied the impact of a symptomless viral infection on the epigenetic status of the host genome. We focused our attention on the interaction between Nicotiana benthamiana and Pelargonium line pattern virus (PLPV, family Tombusviridae), and analyzed cytosine methylation in the repetitive genomic element corresponding to ribosomal DNA (rDNA). Through a combination of bisulfite sequencing and RT-qPCR, we obtained data showing that PLPV infection gives rise to a reduction in methylation at CG sites of the rDNA promoter. Such a reduction correlated with an increase and decrease, respectively, in the expression levels of some key demethylases and of MET1, the DNA methyltransferase responsible for the maintenance of CG methylation. Hypomethylation of rDNA promoter was associated with a five-fold augmentation of rRNA precursor levels. The PLPV protein p37, reported as a suppressor of post-transcriptional gene silencing, did not lead to the same effects when expressed alone and, thus, it is unlikely to act as suppressor of transcriptional gene silencing. Collectively, the results suggest that PLPV infection as a whole is able to modulate host transcriptional activity through changes in the cytosine methylation pattern arising from misregulation of methyltransferases/demethylases balance.

Impact of lipoprotein(a) levels on angiographic severity of femoropopliteal lesions

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Yanaka ◽  
H Akahori ◽  
T Imanaka ◽  
K Miki ◽  
N Yoshihara ◽  
...  
Keyword(s):  
De Novo ◽  
Independent Predictor ◽  
Lesion Length ◽  
Peripheral Artery ◽  
Lipoprotein A ◽  
Class D ◽  
Artery Disease ◽  
Peripheral Arterial ◽  
The Impact ◽  
Severe Calcification

Abstract Background High lipoprotein(a) [Lp(a)] levels are a risk factor for peripheral artery disease (PAD). However, the association between Lp(a) levels and angiographic severity of PAD has not been systematically studied. Purpose The aim of this study was to assess the impact of Lp(a) levels on angiographic severity of femoropopliteal lesions in patients with PAD. Methods We retrospectively analyzed a single-center database including 108 patients (74±8 years, 69% male) who underwent endovascular therapy for de novo femoropopliteal lesions and measured Lp(a) levels before therapy between June 2016 and September 2019. Patients were divided into low Lp(a) [LP(a) <30 mg/dL; 77 patients] and high Lp(a) [LP(a) ≥30 mg/dL; 31 patients] groups. Trans-Atlantic Inter-Society Consensus (TASC) II classification, calcification [referring to peripheral arterial calcium scoring system (PACSS) classification] and lesion length were compared between the groups. Results Median Lp(a) was 16 (7–31) mg/dL.The prevalence of TASC II class D (13% vs 38%, P<0.01) and severe calcification (PACSS 4) (6% vs 23%, P=0.02) was significantly higher and lesion length was longer (123±88 mm vs 175±102 mm, P<0.01) in the high Lp(a) group than in the low Lp(a) group.(Table and Figure) In multivariate analysis, Lp(a)≥30 was an independent predictor for TASC II class D (HR=3.67, P=0.02) and PACSS 4 (HR=4.97, P=0.02) prevalence. Conclusion Lp(a) was associated with angiographic severity of femoropopliteal lesions in patients with PAD. Comparison of angiographic severity Funding Acknowledgement Type of funding source: None

Sign in / Sign up

Export Citation Format

Share Document