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1.
BMC Vet Res ; 18(1): 392, 2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2108779

ABSTRACT

BACKGROUND: Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, has become the major causative agent of acute gastroenteritis in piglets since 2010 in China. RESULTS: In the current study, 91 complete spike (S) gene sequences were obtained from PEDV positive samples collected from 17 provinces in China from March 2020 to March 2021. A phylogenetic analysis showed that 92.3% (84 out of 91) of the identified strains belonged to GII subtype, while 7.7% (7 out of 91) were categorized as S-INDEL like strains and grouped within GI-c clade. Based on a recombination analysis, six of S-INDEL like strains were recombinant strains originated from S-INDEL strain FR/001/2014 and virulent strain AJ1102. In addition, PEDV variant strains (CH/GDMM/202012, CH/GXDX/202010 et al) carrying novel insertions (360QGRKS364 and 1278VDVF1281) in the S protein were observed. Furthermore, the deduced amino acid sequences for the S protein showed that multiple amino acid substitutions in the antigenic epitopes in comparison with the vaccine strains. CONCLUSIONS: In conclusion, these data provide novel molecular evidence on the epidemiology and molecular diversity of PEDV in 2020-2021. This information may help design a strategy for controlling and preventing the prevalence of PEDV variant strains in China.


Subject(s)
Coronavirus Infections , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Swine , Phylogeny , Swine Diseases/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/veterinary , Amino Acid Sequence , China/epidemiology , Spike Glycoprotein, Coronavirus/genetics
2.
Viruses ; 14(10)2022 09 21.
Article in English | MEDLINE | ID: covidwho-2099841

ABSTRACT

The gammacoronavirus avian infectious bronchitis virus (IBV) is a highly contagious respiratory pathogen of primary economic importance to the global poultry industry. Two IBV lineages (GI-11 and GI-16) have been widely circulating for decades in South America. GI-11 is endemic to South America, and the GI-16 is globally distributed. We obtained full-length IBV genomes from Argentine and Uruguayan farms using Illumina sequencing. Genomes of the GI-11 and GI-16 lineages from Argentina and Uruguay differ in part of the spike coding region. The remaining genome regions are similar to the Chinese and Italian strains of the GI-16 lineage that emerged in Asia or Europe in the 1970s. Our findings support that the indigenous GI-11 strains recombine extensively with the invasive GI-16 strains. During the recombination process, GI-11 acquired most of the sequences of the GI-16, retaining the original S1 sequence. GI-11 strains with recombinant genomes are circulating forms that underwent further local evolution. The current IBV scenario in South America includes the GI-16 lineage, recombinant GI-11 strains sharing high similarity with GI-16 outside S1, and Brazilian GI-11 strains with a divergent genomic background. There is also sporadic recombinant in the GI-11 and GI-16 lineages among vaccine and field strains. Our findings exemplified the ability of IBV to generate emergent lineage by using the S gene in different genomic backgrounds. This unique example of recombinational microevolution underscores the genomic plasticity of IBV in South America.


Subject(s)
Coronavirus Infections , Infectious bronchitis virus , Poultry Diseases , Animals , Infectious bronchitis virus/genetics , Chickens , Phylogeny , Mutation , Recombination, Genetic , Brazil
3.
Animals (Basel) ; 12(21)2022 Oct 27.
Article in English | MEDLINE | ID: covidwho-2089981

ABSTRACT

Swine enteric disease is the predominant cause of morbidity and mortality, and viral species involved in swine enteric disease include rotaviruses and coronaviruses, among others. Awareness of the circulating porcine rotavirus group C (PoRVC) in pig herds is critical to evaluate the potential impact of infection. At present, due to the lack of disease awareness and molecular diagnostic means, the research on RVC infection in China is not well-studied. In this study, diarrhea samples collected from pig farms were detected positive for RVC by PCR, and the full-length RVC was not previously reported for Chinese pig farms. This rotavirus strain was designated as RVC/Pig/CHN/JS02/2018/G6P6. A natural recombination event was observed with breakpoints at nucleotides (nt) 2509 to 2748 of the VP2 gene. Phylogenetic analysis based on nsp1 revealed that a new branch A10 formed. Collectively, our data suggest a potentially novel gene recombination event of RVC in the VP2 gene. These findings provide a new insight into the evolution of the rotavirus.

4.
Gene Rep ; 29: 101703, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2086235

ABSTRACT

The genetic variability of SARS-CoV-2 (genus Betacoronavirus, family Coronaviridae) has been scrutinized since its first detection in December 2019. Although the role of structural variants, particularly deletions, in virus evolution is little explored, these genome changes are extremely frequent. They are associated with relevant processes, including immune escape and attenuation. Deletions commonly occur in accessory ORFs and might even lead to the complete loss of one or more ORFs. This scenario poses an interesting question about the origin and spreading of extreme structural rearrangements that persist without compromising virus viability. Here, we analyze the genome of SARS-CoV-2 in late 2021 in Uruguay and identify a Delta lineage (AY.20) that experienced a large deletion (872 nucleotides according to the reference Wuhan strain) that removes the 7a, 7b, and 8 ORFs. Deleted viruses coexist with wild-type (without deletion) AY.20 and AY.43 strains. The Uruguayan deletion is like those identified in Delta strains from Poland and Japan but occurs in a different Delta clade. Besides providing proof of the circulation of this large deletion in America, we infer that the 872-deletion arises by the consecutive occurrence of a 6-nucleotide deletion, characteristic of delta strains, and an 866-nucleotide deletion that arose independently in the AY.20 Uruguayan lineage. The largest deletion occurs adjacent to transcription regulatory sequences needed to synthesize the nested set of subgenomic mRNAs that serve as templates for transcription. Our findings support the role of transcription sequences as a hotspot for copy-choice recombination and highlight the remarkable dynamic of SARS-CoV-2 genomes.

5.
Med (N Y) ; 2022 Oct 20.
Article in English | MEDLINE | ID: covidwho-2076533

ABSTRACT

BACKGROUND: Between November 2021 and February 2022, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants co-circulated in the United States, allowing for co-infections and possible recombination events. METHODS: We sequenced 29,719 positive samples during this period and analyzed the presence and fraction of reads supporting mutations specific to either the Delta or Omicron variant. FINDINGS: We identified 18 co-infections, one of which displayed evidence of a low Delta-Omicron recombinant viral population. We also identified two independent cases of infection by a Delta-Omicron recombinant virus, where 100% of the viral RNA came from one clonal recombinant. In the three cases, the 5' end of the viral genome was from the Delta genome and the 3' end from Omicron, including the majority of the spike protein gene, though the breakpoints were different. CONCLUSIONS: Delta-Omicron recombinant viruses were rare, and there is currently no evidence that Delta-Omicron recombinant viruses are more transmissible between hosts compared with the circulating Omicron lineages. FUNDING: This research was supported by the NIH RADx initiative and by the Centers for Disease Control Contract 75D30121C12730 (Helix).

6.
Annu Rev Virol ; 9(1): 139-156, 2022 09 29.
Article in English | MEDLINE | ID: covidwho-2070601

ABSTRACT

Predicting the evolution of virus host range has proven to be extremely difficult, in part because of the sheer diversity of viruses, each with unique biology and ecological interactions. We have not solved this problem, but to make the problem more tractable, we narrowed our focus to three traits intrinsic to all viruses that may play a role in host-range evolvability: mutation rate, recombination rate, and phenotypic heterogeneity. Although each trait should increase evolvability, they cannot do so unbounded because fitness trade-offs limit the ability of all three traits to maximize evolvability. By examining these constraints, we can begin to identify groups of viruses with suites of traits that make them especially concerning, as well as ecological and environmental conditions that might push evolution toward accelerating host-range expansion.


Subject(s)
Host Specificity , Viruses , Viruses/genetics
7.
Transbound Emerg Dis ; 69(5): e2312-e2317, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2053014

ABSTRACT

Lumpy skin disease virus causes a debilitating pox disease of domesticated cattle and water buffalos. In the last decade, LSDV has spread from Africa into the Middle East, Europe and most recently Asia. As of 2017, atypical outbreaks caused by novel LSDV strains were reported in Russia, followed by China and Vietnam between 2018 and 2020. In this work, we describe another unique recombinant LSDV strain recovered from Tyumen, Russia in 2019. Typing of the virus using currently available qPCR protocols produced inconclusive results and subsequently the complete genome of the isolate was determined. The consensus genome contained statistically significant signals of possible recombination events between parental strains KSGPO-240/Kenya/1958 and the live attenuated vaccine LW/1958. The novel strain carries 25 unique breakpoints different from the known recombinant strains. Additionally, the findings reiterate the importance of complete genome sequencing when analysing outbreak samples caused in particular by mosaic LSDV, in contrast to only performing specified qPCRs.


Subject(s)
Cattle Diseases , Lumpy Skin Disease , Lumpy skin disease virus , Animals , Cattle , Cattle Diseases/epidemiology , Disease Outbreaks/veterinary , Kenya , Lumpy Skin Disease/epidemiology , Lumpy Skin Disease/prevention & control , Russia/epidemiology , Vaccines, Attenuated
8.
Annals of Oncology ; 33:S657, 2022.
Article in English | EMBASE | ID: covidwho-2041523

ABSTRACT

Background: The poly(ADP-ribose) polymerase inhibitor niraparib showed clinical activity in advanced gBRCAm ovarian and breast cancers. LUZERN aims to assess the effectiveness of niraparib plus AI in HR+/HER2–, AI-resistant ABC with a pathogenic variant in homologous recombination-related genes. Here we report findings from the stage 1 interim analysis. Methods: This open-label, single-arm, Simon’s 2-stage, phase II trial is enrolling HR+/HER2– ABC patients (pts) with gBRCAm (cohort A;n=6 in stage 1, n=7 in stage 2) and gBRCA wild-type/HRd (cohort B;n=9 in stage 2). Pts had to have received ≤1 prior line of chemotherapy for ABC, 1–2 prior lines of endocrine therapy for early or ABC with secondary endocrine resistance to the last AI regimen. Pts receive niraparib (200/300mg daily orally) plus AI (same agent given with the prior regimen) on each 28-day cycle. Primary endpoint: clinical benefit rate (CBR) as per RECIST 1.1. Secondary endpoints: overall response rate, progression-free survival (PFS), and safety per CTCAE 5.0. If ≥1/6 pts experienced clinical benefit, the trial should proceed to stage 2. Results: Six pts were enrolled in stage 1. Median age was 46 years (range 32–76), 66.7% of pts had visceral disease, and 83.3% had received prior CDK4/6 inhibitor-containing regimen for ABC. At data cut-off, 50.0% of pts were ongoing and median duration of treatment was 4.6 months (range 2.4–5.7). One patient achieved complete response, meeting the criterion to proceed to stage 2. Median investigator-assessed PFS was 5.3 months (95%CI 3.9–NA). The most frequent adverse events (AEs) of any grade (G) were nausea (3 [50.0%]), neutropenia (2 [33.3%];16.7% G3), constipation (2 [33.3%]), and vomiting (1 [16.7%]). Serious AEs occurred in 3 pts (50.0%;G3 COVID-19 pneumonia;G3 pseudomonal bacteriemia;G2 sacral pain). No treatment-related discontinuations/deaths were reported. Conclusions: Niraparib plus AI showed preliminary activity with a tolerable safety profile in gBRCAm HR+/HER2– AI-resistant ABC pts. Based on the steering committee recommendation, enrolment in cohorts A and B is ongoing. Clinical trial identification: ClinicalTrials.gov identifier: NCT04240106. Legal entity responsible for the study: MEDSIR. Funding: GlaxoSmithKline. Disclosure: J.Á. García Saenz: Financial Interests, Personal, Advisory Board: Seagen, Gilead;Financial Interests, Personal, Invited Speaker: Novartis, Celgene, Eli Lilly, Eisai, AstraZeneca, Daiichi Sankyo, MSD, Exact Sciences;Financial Interests, Institutional, Funding: AstraZeneca. J. De la Haba Rodriguez: Financial Interests, Personal, Other, Consultant and Advisory Role, Research Funding and Speaking: Pfizer, Novartis, Roche, Lilly;Financial Interests, Personal, Other, grant support: Pfizer. J.E. Ales Martínez: Financial Interests, Personal, Other, travel grant: Pfizer;Financial Interests, Personal, Research Grant: MEDSIR. E. Alba Conejo: Financial Interests, Personal, Advisory Role: Roche, Novartis, Pfizer, Lilly, BMS, Astrazeneca, Pierre Fabre, Daiichi, Exact Sciences;Financial Interests, Personal, Research Grant: Pfizer. J. Balmaña: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer;Financial Interests, Institutional, Other, Steering committee member: AstraZeneca;Financial Interests, Institutional, Principal Investigator: Medsir, Pfizer. J.M. Perez Garcia: Financial Interests, Personal, Advisory Role: Lilly,Roche, Eisai, Daichii Sankyo, AstraZeneca, Seattle Genetics, Medsir;Financial Interests, Personal, Other, travel expenses: Roche. M. Sampayo-Cordero: Financial Interests, Personal, Other, honoraria: Medsir, Syntax for Science, Optimapharm, and Ability pharma;Financial Interests, Personal, Research Grant: Medsir;Financial Interests, Personal, Other, travel expenses: Medsir, Syntax for Science, Optimapharm, and Roche;Financial Interests, Personal, Other, consultant: Medsir, Syntax for Science, and Optimapharm;Financial Interests, Personal, Speaker’s Bureau: Medsir;Financial Interests, Personal, Full or part-time Employment: Me sir. A. Malfettone: Non-Financial Interests, Personal, Full or part-time Employment: MEDSIR. J. Cortés: Financial Interests, Personal, Advisory Role: Roche, Celgene, Cellestia, Astrazeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks;Financial Interests, Personal, Other, honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo;Financial Interests, Institutional, Research Grant: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London.;Financial Interests, Personal, Stocks/Shares: MEDSIR, Nektar Pharmaceuticals, Leuko (relative);Financial Interests, Personal, Other, travel, accomodation: Roche, Novartis, Eisai, pfizer, Daiichi Sankyo, Astrazeneca. A. Llombart Cussac: Financial Interests, Personal, Leadership Role: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, and MSD;Financial Interests, Personal, Stocks/Shares: MEDSIR and Initia-Research;Financial Interests, Personal, Advisory Role: Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, GenomicHealth, GSK;Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, and MSD;Financial Interests, Personal, Research Grant: Roche, Foundation Medicine, Pierre-Fabre, and Agendia;Financial Interests, Personal, Other, travel compensation: Roche, Lilly, Novartis, Pfizer, and AstraZeneca. All other authors have declared no conflicts of interest.

9.
Swiss Medical Weekly ; 152:11S, 2022.
Article in English | EMBASE | ID: covidwho-2040882

ABSTRACT

Recombinant Orf virus (rORFV) based vectors are under clinical development for COVID-19 vaccination. Little is known, however, about the cellular correlates of antibody responses to this poxviral vector platform. To monitor antigen-specific B cell responses to vaccination, we adoptively transferred to mice indicator populations of monoclonal B cells recognizing the glycoproteins (GPs) of either vesicular stomatitis virus or lymphocytic choriomeningitis virus and epitope variants thereof. Immunizations of mice with rORFV expressing the respective GPs stimulated the transferred B cells to engage in a protracted germinal center (GC) response, which was maintained longer-term when the delivered antigen was of lower affinity. GPspecific CD8 and CD4 T cells responses were also induced, and the latter included T follicular helper cells (Tfh). These T cell responses contracted over time but re-expanded upon homologous rORFV booster vaccination, alongside with an augmentation in antigen-specific memory B cells. Pre-existing rORFV-specific anti-vector immunity suppressed CD8 T cell responses to ORFV-vectored cargo whereas CD4 T cell and B cell responses were unaffected. Importantly, rORFV-based vaccination conferred long-term antibodymediated protection against VSV challenge. This study demonstrates the versatility of rORFV-vectored vaccination including its capacity to induce substantial GC B cell as well as Tfh responses. Limited interference by anti-vector immunity should facilitate the challenging task of maintaining protective antibody immunity by prime - boost vaccination.

10.
J Comput Biol ; 2022 Sep 20.
Article in English | MEDLINE | ID: covidwho-2037357

ABSTRACT

An accurate understanding of the evolutionary history of rapidly-evolving viruses like SARS-CoV-2, responsible for the COVID-19 pandemic, is crucial to tracking and preventing the spread of emerging pathogens. However, viruses undergo frequent recombination, which makes it difficult to trace their evolutionary history using traditional phylogenetic methods. In this study, we present a phylogenetic workflow, virDTL, for analyzing viral evolution in the presence of recombination. Our approach leverages reconciliation methods developed for inferring horizontal gene transfer in prokaryotes and, compared to existing tools, is uniquely able to identify ancestral recombinations while accounting for several sources of inference uncertainty, including in the construction of a strain tree, estimation and rooting of gene family trees, and reconciliation itself. We apply this workflow to the Sarbecovirus subgenus and demonstrate how a principled analysis of predicted recombination gives insight into the evolution of SARS-CoV-2. In addition to providing confirming evidence for the horseshoe bat as its zoonotic origin, we identify several ancestral recombination events that merit further study.

11.
Zhongguo Yufang Shouyi Xuebao / Chinese Journal of Preventive Veterinary Medicine ; 44(1):108-108, 2022.
Article in English, Chinese | CAB Abstracts | ID: covidwho-2034138

ABSTRACT

Avian infectious bronchitis (IB) is one of the acute and highly contagious upper respiratory tract infectious diseases in poultry caused by the Infectious bronchitis virus (IBV), which significantly affects the health and development of world poultry farming industry. IBV RNA polymerase lacks a complete correctional function and is prone to gene mutation and RNA-RNA recombination during the replication process, resulting in the emergence of new serotypes, genotypes and mutant strains. The continuous generation of recombinant strains through homologous recombination between strains also complicates the prevention and control of IB. Therefore, monitoring the genetic evolutionary characteristics of circulating strains and evaluating the protective effect of commonly used vaccines against local circulating strains of IBV are the keys to preventing and controlling this disease.

12.
Diagnostics (Basel) ; 12(9)2022 Sep 14.
Article in English | MEDLINE | ID: covidwho-2032878

ABSTRACT

We report two cases of SARS-CoV-2 recombinant variant XE detected in nasopharyngeal swabs (NPS) of hospitalized patients with no evident epidemiological link in Lazio, Central Italy. Whole-Genome Sequencing (WGS) performed on an Ion Torrent GSS5 platform according to Italian flash surveys showed genomes corresponding to the PANGOLIN unclassified lineage and the Nextclade XE clade. Further analyses were then carried out to investigate more deeply the genetic characteristics of these XE-like sequences. When phylogenetic trees, by using IQ-TREE, were built splitting the genome into two regions according to the putative XE recombination site, the upstream and downstream regions were seen to be clustered near BA.1 and BA.2 sequences, respectively. However, our XE-like sequences clustered separately, with a significant bootstrap, from the classified European and Italian XE strains, although the recombination site between BA.1 and BA.2 was identified at the nucleotide site 11556 by RDP4 software, consistent with the putative XE breakpoint. These findings show the risk of the introduction of novel recombinant variants of SARS-CoV-2 and the existence of XE-like strains, phylogenetically separated, that could make their exact taxonomy difficult. It follows the need for continued SARS-CoV-2 surveillance by WGS.

13.
Front Vet Sci ; 9: 931272, 2022.
Article in English | MEDLINE | ID: covidwho-2032824

ABSTRACT

New variants of infectious bronchitis viruses (IBVs; Coronaviridae) continuously emerge despite routine vaccinations. Here, we report genome sequence variations of IBVs identified by random non-targeted next generation sequencing (NGS) of vaccine and field samples collected on FTA cards from commercial flocks in Mexico in 2019-2021. Paired-ended sequencing libraries prepared from rRNA-depleted RNAs were sequenced using Illumina MiSeq. IBV RNA was detected in 60.07% (n = 167) of the analyzed samples, from which 33 complete genome sequences were de novo assembled. The genomes are organized as 5'UTR-[Rep1a-Rep1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b]-3'UTR, except in eight sequences lacking non-structural protein genes (accessory genes) 4b, 4c, and 6b. Seventeen sequences have auxiliary S2' cleavage site located 153 residues downstream the canonically conserved primary furin-specific S1/S2 cleavage site. The sequences distinctly cluster into lineages GI-1 (Mass-type; n = 8), GI-3 (Holte/Iowa-97; n = 2), GI-9 (Arkansas-like; n = 8), GI-13 (793B; n = 14), and GI-17 (California variant; CAV; n = 1), with regional distribution in Mexico; this is the first report of the presence of 793B- and CAV-like strains in the country. Various point mutations, substitutions, insertions and deletions are present in the S1 hypervariable regions (HVRs I-III) across all 5 lineages, including in residues 38, 43, 56, 63, 66, and 69 that are critical in viral attachment to respiratory tract tissues. Nine intra-/inter-lineage recombination events are present in the S proteins of three Mass-type sequences, two each of Holte/Iowa-97 and Ark-like sequence, and one each of 793B-like and CAV-like sequences. This study demonstrates the feasibility of FTA cards as an attractive, adoptable low-cost sampling option for untargeted discovery of avian viral agents in field-collected clinical samples. Collectively, our data points to co-circulation of multiple distinct IBVs in Mexican commercial flocks, underscoring the need for active surveillance and a review of IBV vaccines currently used in Mexico and the larger Latin America region.

14.
EcoMat ; 4(5), 2022.
Article in English | ProQuest Central | ID: covidwho-2013485

ABSTRACT

The gradual depletion of fossil fuel reserves that contribute to ~85% of global energy production and release of toxic effluents urges the transformation toward renewable fuels. Thus, the sustainable utilization of sunlight for water splitting and CO2 reduction with heterogeneous photocatalysts has come to light. As a semiconductor photocatalyst, ZnIn2S4 has hit the limelight owing to its narrow bandgap and visible‐light‐responsive properties. However, the limitations of ZnIn2S4 include limited active sites, fast charge‐carrier recombination, and low photoconversion efficiency. Beginning from the fundamental photocatalytic mechanism, this review then provides in‐depth insights into several modification strategies of ZnIn2S4, extending from defect engineering, facet engineering, cocatalyst loading to junction engineering, enabling the synergistic construction of high‐performance ZnIn2S4‐based systems. Subsequently, the structure‐performance relation of ZnIn2S4‐based photocatalysts for hydrogen evolution (HER), overall water splitting (OWS), and CO2 reduction applications in the last 4 years will be discussed and concluded by the future perspectives of this frontier.

15.
Advanced Therapeutics ; 5(8), 2022.
Article in English | EMBASE | ID: covidwho-2007088

ABSTRACT

Cancer gene therapy based on various gene delivery vectors has some potential but also has obvious disadvantages. In this study, a new M13 phage-based oncolytic virus is constructed that carried the RGD peptides to target tumor cells and the 3C gene of Seneca Valley virus (SVV) preceded by a eukaryotic initial transcriptional region (ITR) to transcribe an oncolytic protein to kill tumor cells. Recombinant virus particles of 1200 nm in length are obtained in large quantities by transfecting the recombinant M13 phage plasmid into the host BL2738 and are investigated in vitro in tumor cells and in vivo in tumor-bearing mice to evaluate their antitumor effect. The experiments using Hela cells confirm that the engineered M13 phage can target and enter Hela cells, and express the SVV 3C protein, resulting in apoptosis of target cells by upregulating the expression of caspase 3. Furthermore, the results of experiments in vivo also show that the recombinant phage significantly inhibits the enhanced tumor volume in nude mice compared to the control groups. The M13 phage may be engineered to fuse with a variety of oncolytic proteins to inhibit the growth of tumor cells in the future, providing a promising phage-based targeted oncolytic reagent.

16.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2005865

ABSTRACT

Sparked by the development of genome sequencing technology, the quantity and quality of data handled in immunological research have been changing dramatically. Various data and database platforms are now driving the rapid progress of machine learning for immunological data analysis. Of various topics in immunology, T cell receptor repertoire analysis is one of the most important targets of machine learning for assessing the state and abnormalities of immune systems. In this paper, we review recent repertoire analysis methods based on machine learning and deep learning and discuss their prospects.

17.
Arhiv za Farmaciju ; 72(2):105-126, 2022.
Article in English | EMBASE | ID: covidwho-1998002

ABSTRACT

As research related to healthspan and lifespan has become a hot topic, the necessity for a reliable and practical biomarker of aging (BoA), which can provide information about mortality and morbidity risk, along with remaining life expectancy, has increased. The chromosome terminus non-coding protective structure that prevents genomic instability is called a telomere. The continual shortening of telomeres, which affects their structure as well as function, is a hallmark of agedness. The aforementioned process is a potential cause of age-related diseases (ARDs), leading to a bad prognosis and a low survival rate, which compromise health and longevity. Hence, studies scrutinizing the BoAs often include telomere length (TL) as a prospective candidate. The results of these studies suggest that TL measurement can only provide an approximate appraisal of the aging rate, and its implementation into clinical practice and routine use as a BoA has many limitations and challenges. Nevertheless, measuring TL while determining other biomarkers can be used to assess biological age. This review focuses on the importance of telomeres in health, senescence, and diseases, as well as on summarizing the results and conclusions of previous studies evaluating TL as a potential BoA.

18.
Int J Mol Sci ; 23(16)2022 Aug 14.
Article in English | MEDLINE | ID: covidwho-1987832

ABSTRACT

After the recent emergence of SARS-CoV-2 infection, unanswered questions remain related to its evolutionary history, path of transmission or divergence and role of recombination. There is emerging evidence on amino acid substitutions occurring in key residues of the receptor-binding domain of the spike glycoprotein in coronavirus isolates from bat and pangolins. In this article, we summarize our current knowledge on the origin of SARS-CoV-2. We also analyze the host ACE2-interacting residues of the receptor-binding domain of spike glycoprotein in SARS-CoV-2 isolates from bats, and compare it to pangolin SARS-CoV-2 isolates collected from Guangdong province (GD Pangolin-CoV) and Guangxi autonomous regions (GX Pangolin-CoV) of South China. Based on our comparative analysis, we support the view that the Guangdong Pangolins are the intermediate hosts that adapted the SARS-CoV-2 and represented a significant evolutionary link in the path of transmission of SARS-CoV-2 virus. We also discuss the role of intermediate hosts in the origin of Omicron.


Subject(s)
COVID-19 , Chiroptera , Animals , China , Pangolins/genetics , Phylogeny , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/metabolism
19.
Cancer Research ; 82(12), 2022.
Article in English | EMBASE | ID: covidwho-1986481

ABSTRACT

Purpose: The estrogen receptor (ER) is expressed in over 80% of breast tumors and has been shown to be a significant driver of breast cancer (BC) pathogenesis and therefore a target of effective first-line therapies. While both ionizing radiation (RT) and endocrine therapies (ET) are used for the treatment of ER+ BC, the effect of ET on tumor radiosensitization remains unclear, with concerns it may be radioprotective based on G1 cell arrest with ET treatment. Here we assessed the efficacy and mechanism of ER-mediated radiosensitization using various pharmacologic approaches in ER+ BC. Methods: Radiosensitization with ER inhibitors (tamoxifen [TAM], fulvestrant [FULV], AZD9496) was assessed using clonogenic survival assays. DNA damage was assessed by the neutral comet assay. Efficiency of homologous recombination (HR) or non-homologous end joining (NHEJ) as well as changes in cell cycle, apoptosis, and senescence were assessed. The efficacy of TAM with RT in vivo was assessed with an MCF-7 xenograft model. Results: The selective estrogen receptor modulator TAM radiosensitized ER+ MCF-7 (enhancement ratio [enhR]: 1.14-1.50) and T47D (enhR: 1.33-1.60) cells but not ER-negative SUM-159 cells (enhR: 0.99-1.02). The selective estrogen receptor degrader (SERD) FULV had similar radiosensitization effects in MCF-7 (enhR: 1.33-1.76) and T47D cells (enhR: 0.97-2.81) with no radiosensitization observed in SUM-159 cells (enhR: 1.01-1.03). The novel oral SERD AZD9496 radiosensitized MCF-7 cells (enhR: 1.36-1.56). MCF-7 cells treated with TAM and RT had an increase in dsDNA breaks compared to RT alone as measured by the comet assay (p<0.05) and a decrease in NHEJ-mediated repair with TAM (p<0.05). No changes were observed in HR-mediated repair by Rad51 foci or a reporter (p=NS). RT alone and in combination with TAM or FULV induced similar levels of cell cycle arrest, suggesting that radiosensitization with the combination therapy is cell-cycle independent. There were no significant changes in apoptosis with TAM, FULV, RT, or the combination (p=NS). Although TAM or FULV did induce senescence, ET with RT increased senescence induction (p<0.05). In vivo, combination RT and TAM led to a significant delay in days to tumor doubling (control: 17, TAM: 40, RT: 32, TAM+RT: undefined;p<0.0001), and a significant difference in tumor growth between mice treated with TAM or RT alone compared combination treatment, with no increased toxicities or skin lesions from the combination treatment. Conclusion: Our data suggest that TAM, FULV, or AZD9496 can radiosensitize ER+ breast tumors, and these agents with RT may be more effective for radiosensitization. This work also supports further clinical investigation of the timing of RT for patients receiving ET, including using ET during RT, especially as initiating ET prior to RT has been increasingly utilized as a bridging therapy followed by concurrent ET+RT during the COVID-19 pandemic.

20.
Front Vet Sci ; 9: 842179, 2022.
Article in English | MEDLINE | ID: covidwho-1987612

ABSTRACT

Avian coronavirus infectious bronchitis virus (IBV) is a respiratory pathogen of chickens, resulting in severe economic losses in the poultry industry. This study aimed to monitor and isolate the molecular identity of IBV in broiler flocks with respiratory symptoms in eight provinces of China. In total, 910 samples (oropharyngeal and cloacal mixed swabs) from broiler flocks showed IBV positive rates of 17.6% (160/910) using PCR assay. Phylogenetic analysis of the complete S1 genes of 160 IBV isolates was performed and revealed that QX-type (GI-19), TW-type (GI-7), 4/91-type (GI-13), HN08-type (GI-22),TC07-2-type (GVI-1), and LDT3-type (GI-28) exhibited IBV positive rates of 58.15, 25, 8.12, 1.86, 5.62, and 1.25%. In addition, recombination analyses revealed that the four newly IBV isolates presented different recombination patterns. The CK/CH/JS/YC10-3 isolate likely originated from recombination events between strain YX10 (QX-type) and strain TW2575-98 (TW-type), the pathogenicity of which was assessed, comparing it with strain GZ14 (TW-type) and strain CK/CH/GD/JR07-7 (QX-type). The complete S1 gene data from these isolates indicate that IBV has consistently evolved through genetic recombination or mutation, more likely changing the viral pathogenicity and leading to larger outbreaks in chick populations, in China.

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