Current research progress on the viral immune evasion mechanisms of African swine fever virus

African swine fever(ASF),caused by the ASF virus(ASFV),is an acute,severe,and highly contagious infectious disease in domestic pigs and wild boars.Domestic pigs infected with a virulent ASFV strain can have morbidity and mortality rates of up to 100%.The epidemic of ASF has caused serious economic losses to the global pig industry.Currently,there is no safe and efective vaccine or specifc drug for treating ASF.Therefore,ASFV still poses a great threat to pig factories.ASFV is a double-stranded DNA virus with a complex icosahedral multilayer structure.The ASFV genome contains 150-170 open reading frames(ORFs)that encode 150-200 proteins.Some ASFV-encoded proteins are involved in virus invasion,genome replication,DNA repair,and virion formation.Some ASFV proteins execute immunomodulatory functions by regulating the host antiviral innate immune response.Accumulating studies have shown that the immunomodulatory functions of ASFV genes are closely related to the virulence and pathogenicity of ASFV isolates.This review summarizes the research advances on ASFV immune evasion mechanisms in African swine fever patients and provides new insights for developing attenuated live vaccine candidates to prevent and control ASF.

Unveiling the global reach of African anthrax research:a bibliometric study

Anthrax is a zoonotic bacterial disease caused by Bacillus anthracis.It poses significant threat to humans through contact with infected animals or their by-products.Concerns arise from its long-lasting spore viability and lethality,fuelling its biowarfare potential.Recent anthrax outbreaks across multiple African nations prompted this bibliometric study.The aim of the study was to assess the contributions of African countries,institutions,authors,research funding,and collaborations,while identifying research trends and gaps.We conducted an extensive bibliometric analysis of anthrax-related research publications in Africa from 1923 to 2023,utilizing the Scopus database and VOSviewer.The study covered 364 publications from 32 African countries,accumulating 5,636 citations at an average of 15.5 citations per article,with research articles comprising 88.5%of the corpus.The publication growth rate from 1923 to 2023 was modest at 8.3%,indicating gradual advancement.Notably,there was a significant surge in publications between 2011 and 2023,accounting for 73.1%of total publications.The African research contributions,were categorized into five thematic focuses:ecological dynamics and host interactions,human-livestock anthrax interface,molecular insights into bacterial activity and treatment strategies,collaborative approaches for zoonotic disease prevention,and antibody response and vaccination strategies.Leading institutional contributors included the University of Pretoria and the University of KwaZulu-Natal.Collaborations extended globally to 35 non-African countries,with significant involvement from the United States,United Kingdom,and Germany.Strong African partnerships,especially between Kenya,Nigeria,and South Africa,emerged.The top 10 cited papers explored diverse aspects,including disease impact on wildlife and innovative control strategies,underscoring the importance of multidisciplinary approaches.South Africa played a prominent role,contributing 95 publications and securing funding from various sources,including the National Research Foundation.Collaborations with global institutions highlighted its commitment.This study unveils the dynamic landscape of anthrax research in Africa,emphasizing the pivotal role of collaboration,multidisciplinary One Health approaches,and global partnerships in enhancing research outcomes.Ongoing research and practical solutions for human and animal health remain imperative.

Deletion of Salmonella pathogenicity islands SPI-1, 2 and 3 induces substantial morphological and metabolic alternation and protective immune potential

The Salmonella pathogenicity islands(SPIs) play crucial roles in the progression of Salmonella infection. In this study, we constructed an improved λ Red homologous recombination system to prepare single and triple deletion mutants of 3 prominent SPIs(SPI-1, 2, and 3), aiming at the impact of deletion on morphology, carbon source metabolism, adhesion and invasion capacity, in vivo colonization, and immune efficacy in chicks. Our examination revealed that the surface of the single deletion mutants(SM6ΔSPI1, ΔSPI2, and ΔSPI3) exhibited a more rugged texture and appeared to be enveloped in a layer of transparent colloid, whereas the morphology of the triple deletion mutant(SM6ΔSPI1&2&3) remained unaltered when compared to the parent strain. The carbon metabolic spectrum of the SPI mutants underwent profound alterations, with a notable and statistically significant modification observed in 30 out of 95 carbon sources, primarily carbohydrates(17 out of 30). Furthermore, the adhesion capacity of the 4 mutants to Caco-2 cells was significantly reduced when compared to that of the parent strain. Moreover,the invasion capacity of mutants SM6ΔSPI1 and SM6ΔSPI1&2&3 exhibited a substantial decrease, while it was enhanced to varying degrees for SM6ΔSPI3 and SM6ΔSPI2. Importantly, none of the 4 mutants induced any clinical symptoms in the chicks. However, they did transiently colonize the spleen and liver. Notably, the SM6ΔSPI1&2&3mutant was rapidly cleared from both the spleen and liver within 8 days post-infection and no notable pathological changes were observed in the organs. Additionally, when challenged, the mutants immunized groups displayed a significant increase in antibody levels and alterations in the CD3+CD4+ and CD3+CD8+ subpopulations, and the levels of IL-4 and IFN-γ cytokines in the SM6ΔSPI1&2&3 immunized chicken serum surpassed those of other groups.In summary, the successful construction of the 4 SPI mutants lays the groundwork for further exploration into the pathogenic(including metabolic) mechanisms of SPIs and the development of safe and effective live attenuated Salmonella vaccines or carriers.

A Semi-quantitative Serological Method to Assess the Potency of Inactivated Rabies Vaccine for Veterinary Use

Potency is one of the most important indexes of inactivated vaccines.A number of methods have been established to assay the potency,of which the NIH test and single-dose mouse protection test are the "prescribed methods".Here,we report a method to semi-quantitatively assay the potency of an inactivated rabies vaccine,which uses fewer animals and takes less time to complete.Depending on the quality requirements of a vaccine(e.g.minimum potency),a rabies reference vaccine is,for example,diluted to the minimum potency,and 50 μL of the dilution is taken to inoculate 10 mice.The same amount of the test rabies vaccine is inoculated into another 10 mice.After two weeks,all mice are bled and serum samples are assayed for viral neutralizing antibody by the fluorescent antibody virus neutralization(FAVN) test.By comparing the median and interquartile range of antibody titers of the reference vaccine with those of the test vaccine,the test vaccine potency can be semi-quantitatively judged as to whether it is in accord with the required quality.The reliability of this method was also confirmed in dogs.The procedure can be recommended for batch potency testing during inactivated rabies vaccine production.

Research Progress in NTPase of Toxoplasma gondii and Other Protozoa

Nucleoside triphosphate hydrolase （NTPase） is a multifunctional enzymatic family widely existing in vivo. They can hydrolyze NTP to NMP or dNTP to dNMP to produce energy. In this article, the structure of Toxoplasma gondii NTPase is analyzed. The research progress in NT- Pase of Toxoplasrna gondii, Trypanosoma cruzi, Sarcocystis neurona and Neospora caninum was briefly reviewed.

Five years Retrospective Study of Avian Coccidiosis in a Veterinary Clinic Bukuru Plateau State Nigeria

This study was conducted to evaluate the incidence of avian coccidiosis and its associated various risk factors such as age,type of birds and season in a private veterinary clinic in Bukuru,Plateau State Ngeria.A total of 9406 cases during 2013–2017 were analysed and 1556 of them were positive for coccidiosis.There are several reports on the prevalence of avian coccidiosis by previous researchers;however,in this study we evaluated the prevalence of avian coccidiosis in the study area and its economic impacts.Total prevalence of 12.14%in 2013,18.78%in 2014,18.21%in 2015,16.82%in 2016 and 19.07%in 2017 were reported.An overall prevalence of 85.02%was recorded.The average prevalence of coccidiosis based on this five years study is 17%.The association between coccidiosis and age of the birds was determined and age 5-8 weeks becomes most effective period with wet season having high percentage prevalence of coccidiosis.Based on the type of birds,coccidiosis is prevalence almost in equal proportion in both broilers and layers.The losses caused by avian coccidiosis could be both direct and indirect components which may include the cost of control measures,inadequate good hygiene practices,production losses and lack of prophylaxis treatment.The control of avian coccidiosis can be achieved through good sanitary measures by avoiding water spillage on the pen floor,overcrowded stocking density,the use of prophylaxis-anticoccidials and proper good vaccination practices.

Control of highly pathogenic avian influenza through vaccination

The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian influenza virus in vaccinated birds would evolve more rapidly and pose a greater risk to humans.In this review,we summarize the successes in controlling highly pathogenic avian influenza in China and make suggestions regarding the requirements for vaccine selection and effectiveness.In addition,we present evidence that vaccination of poultry not only eliminates human infection with avian influenza virus,but also significantly reduces and abolishes some harmful characteristics of avian influenza virus.

Understanding the spectrum of non-motor symptoms in multiple sclerosis:insights from animal models

Multiple sclerosis is a chronic autoimmune disease of the central nervous system and is generally considered to be a non-traumatic,physically debilitating neurological disorder.In addition to experiencing motor disability,patients with multiple sclerosis also experience a variety of nonmotor symptoms,including cognitive deficits,anxiety,depression,sensory impairments,and pain.However,the pathogenesis and treatment of such non-motor symptoms in multiple scle rosis are still under research.Preclinical studies for multiple sclerosis benefit from the use of disease-appropriate animal models,including experimental autoimmune encephalomyelitis.Prior to understanding the pathophysiology and developing treatments for non-motor symptoms,it is critical to chara cterize the animal model in terms of its ability to replicate certain non-motor features of multiple sclerosis.As such,no single animal model can mimic the entire spectrum of symptoms.This review focuses on the non-motor symptoms that have been investigated in animal models of multiple sclerosis as well as possible underlying mechanisms.Further,we highlighted gaps in the literature to explain the nonmotor aspects of multiple sclerosis in expe rimental animal models,which will serve as the basis for future studies.

Pangenome and multi-tissue gene atlas provide new insights into the domestication and highland adaptation of yaks

Background The genetic diversity of yak,a key domestic animal on the Qinghai-Tibetan Plateau(QTP),is a vital resource for domestication and breeding efforts.This study presents the first yak pangenome obtained through the de novo assembly of 16 yak genomes.Results We discovered 290 Mb of nonreference sequences and 504 new genes.Our pangenome-wide presence and absence variation(PAV)analysis revealed 5,120 PAV-related genes,highlighting a wide range of variety-specific genes and genes with varying frequencies across yak populations.Principal component analysis(PCA)based on binary gene PAV data classified yaks into three new groups:wild,domestic,and Jinchuan.Moreover,we pro-posed a‘two-haplotype genomic hybridization model'for understanding the hybridization patterns among breeds by integrating gene frequency,heterozygosity,and gene PAV data.A gene PAV-GWAS identified a novel gene(Bos-Gru3G009179)that may be associated with the multirib trait in Jinchuan yaks.Furthermore,an integrated transcrip-tome and pangenome analysis highlighted the significant differences in the expression of core genes and the muta-tional burden of differentially expressed genes between yaks from high and low altitudes.Transcriptome analysis across multiple species revealed that yaks have the most unique differentially expressed m RNAs and lnc RNAs(between high-and low-altitude regions),especially in the heart and lungs,when comparing high-and low-altitude adaptations.Conclusions The yak pangenome offers a comprehensive resource and new insights for functional genomic studies,supporting future biological research and breeding strategies.

Emergence of highly pathogenic avian influenza A(H5N8)clade 2.3.4.4b viruses in grebes in Inner Mongolia and Ningxia,China,in 2021

Highly pathogenic avian influenza(HPAI)subtype H5Nx viruses have spread globally and are a major concern for poultry,wild birds,mammals,and even humans(de Vries et al.2015;Zeng et al.2022).The hemagglutinin(HA)genes of H5 subtype viruses have evolved into multiple clades and some of these clades have been further divided into subclades(Cui et al.2022).Clade 2.3.4.4H5N8 HPAI viruses(HPAIVs)have caused several waves of disease outbreaks in wild birds and domestic poultry(Wang et al.2022).

A novel live attenuated vaccine candidate protects chickens against subtype B avian metapneumovirus

Avian metapneumovirus(aMPV) is a highly contagious pathogen that causes acute upper respiratory tract diseases in chickens and turkeys, resulting in serious economic losses. Subtype B aMPV has recently become the dominant epidemic strain in China. We developed an attenuated aMPV subtype B strain by serial passaging in Vero cells and evaluated its safety and efficacy as a vaccine candidate. The safety test showed that after the 30th passage, the LN16-A strain was fully attenuated, as clinical signs of infection and histological lesions were absent after inoculation.The LN16-A strain did not revert to a virulent strain after five serial passages in chickens. The genomic sequence of LN16-A differed from that of the parent wild-type LN16(wtLN16) strain and had nine amino acid mutations. In chickens, a single immunization with LN16-A induced robust humoral and cellular immune responses, including the abundant production of neutralizing antibodies, CD4^(+) T lymphocytes, and the Th1(IFN-γ) and Th2(IL-4 and IL-6)cytokines. We also confirmed that LN16-A provided 100% protection against subtype B aMPV and significantly reduced viral shedding and turbinate inflammation. Our findings suggest that the LN16-A strain is a promising live attenuated vaccine candidate that can prevent infection with subtype B aMPV.

Establishment of an indirect immunofluorescence assay for the detection of African swine fever virus antibodies

African swine fever(ASF)continues to cause enormous economic loss to the global pig industry.Since there is no safe and effective vaccine,accurate and timely diagnosis of ASF is essential to implement control measures.Indirect immunofluorescence assay(IFA)is a gold standard serological method recommended by the World Organization for Animal Health(WOAH).In this study,we used primary fetal kidney cells to establish a wild boar cell line(BK2258)that supported the efficient replication of ASF virus(ASFV)SD/DY-I/21 and showed visible cytopathic effect(CPE).Moreover,using BK2258,we established a sensitive and specific IFA for ASFV antibody detection.To standardize and evaluate the performance of this assay,we used serum samples from pigs infected with the low virulent genotype I SD/DY-I/21 and genotype II HLJ/HRB1/20,and immunized with the vaccine candidate HLJ/18-7GD,field samples,and negative serum samples.The IFA reacted with the ASFV-positive sera and displayed bright fluorescence foci.There was no non-specific green fluorescence due to cellular senescence or other cell damage-causing factors.Compared to a commercial indirect enzyme-linked immunosorbent assay(iELISA),ASFV antibodies were detected 1–4 days earlier using our IFA.The detection limits of the IFA and iELISA for the same ASFV-antibody positive serum samples were 1:25,600 and 1:6,400,respectively,indicating that the IFA is more sensitive than iELISA.The newly established IFA was highly specific and did not cross-react with sera positive for six other important porcine pathogens(i.e.,Classical swine fever virus(CSFV),Porcine reproductive and respiratory syndrome virus(PRRSV),Porcme circovirus type 2(PCV2),Pseudorabies virus(PRV),Foot-and-Mouth disease virus type O(FMDV/O),and Porcine epidemic diarrhea virus(PEDV)).This study thus provides a sensitive,specific,and reliable detection method that is suitable for the serological diagnosis of ASF.

Biology of Hippo signaling pathway:Skeletal muscle development and beyond

Global demand for farm animals and their meat products i.e.,pork,chicken and other livestock meat,is steadily incresing.With the ongoing life science research and the rapid development of biotechnology,it is a great opportunity to develop advanced molecular breeding markers to efficiently improve animal meat production traits.Hippo is an important study subject because of its crucial role in the regulation of organ size.In recent years,with the increase of research on Hippo signaling pathway,the integrative application of multi-omics technologies such as genomics,transcriptomics,proteomics,and metabolomics can help promote the in-depth involvement of Hippo signaling pathway in skeletal muscle development research.The Hippo signaling pathway plays a key role in many biological events,including cell division,cell migration,cell proliferation,cell differentiation,cell apoptosis,as well as cell adhesion,cell polarity,homeostasis,maintenance of the face of mechanical overload,etc.Its influence on the development of skeletal muscle has important research value for enhancing the efficiency of animal husbandry production.In this study,we traced the origin of the Hippo pathway,comprehensively sorted out all the functional factors found in the pathway,deeply analyzed the molecular mechanism of its function,and classified it from a novel perspective based on its main functional domain and mode of action.Our aim is to systematically explore its regulatory role throughout skeletal muscle development.We specifically focus on the Hippo signaling pathway in embryonic stem cell development,muscle satellite cell fate determination,myogenesis,skeletal muscle meat production and organ size regulation,muscle hypertrophy and atrophy,muscle fiber formation and its transformation between different types,and cardiomyocytes.The roles in proliferation and regeneration are methodically summarized and analyzed comprehensively.The summary and prospect of the Hippo signaling pathway within this article will provide ideas for further improving meat production and muscle deposition and developing new molecular breeding technologies for livestock and poultry,which will be helpful for the development of animal molecular breeding.

Inactivated H9N2 vaccines developed with early strains do not protect against recent H9N2 viruses:Call for a change in H9N2 control policy

H9N2 virus has been widely distributed in wild birds and poultry around the world since its first emergence in the United States of America in 1966(Gu et al.2017;Carnaccini and Perez 2020).The virus appeared in chickens in China in the early 1990s,and over the last two decades has gradually become the dominant epidemic subtype(Sun and Liu 2015;Bi et al.2020).Although H9N2 virus infection alone cannot cause severe disease or death in poultry,H9N2 virus-infected birds experience a degree of egg production drop and can be easily infected by other pathogens,thus causing economic losses for poultry industry.

The virulence regulator AbsR in avian pathogenic Escherichia coli has pleiotropic effects on bacterial physiology

Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic E.coli(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and blood.MprA(microcin production regulation,locus A,herein renamed AbsR,a blood survival regulator),a member of the MarR(multiple antibiotic resistance regulator)transcriptional regulator family,governs the expression of capsule biosynthetic genes in human ExPEC and represents a promising druggable target for antimicrobials.However,a deep understanding of the AbsR regulatory mechanism as well as its regulon is lacking.In this study,we present a systems-level analysis of the APEC AbsR regulon using ChIP-Seq(chromatin immunoprecipitation sequencing)and RNA-Seq(RNA sequencing)methods.We found that AbsR directly regulates 99 genes and indirectly regulates 667 genes.Furthermore,we showed that:1)AbsR contributes to antiphagocytotic effects by macrophages and virulence in a mouse model for systemic infection by directly activating the capsular gene cluster;2)AbsR positively impacts biofilm formation via direct regulation of the T2SS(type II secretion system)but plays a marginal role in virulence;and 3)AbsR directly upregulates the acid tolerance signaling system EvgAS to withstand acid stress but is dispensable in ExPEC virulence.Finally,our data indicate that the role of AbsR in virulence gene regulation is relatively conserved in ExPEC strains.Altogether,this study provides a comprehensive analysis of the AbsR regulon and regulatory mechanism,and our data suggest that AbsR likely influences virulence primarily through the control of capsule production.Interestingly,we found that AbsR severely represses the expression of the type I-F CRISPR(clustered regularly interspaced short palindromic repeats)-Cas(CRISPR associated)systems,which could have implications in CRISPR biology and application.

Role of feline ANP32 proteins in regulating polymerase activity of influenza A virus

Recently,increasing natural infection cases and experimental animal challenge studies demonstrated domestic cats are susceptible to multiple subtypes influenza A virus(IAV)infections.Notably,some subtype IAV strains could circulate in domestic cats after cross-species transmission and even infected humans,posing a threat to public health.Host factors related to viral polymerase activity could determine host range of IAV and acidic nuclear phosphoprotein 32(ANP32)is the most important one among them.However,role of cat-derived ANP32 on viral polymerase activity and host range of IAV is still unknown.In the present study,a total of 10 feline ANP32(feANP32)splice variants(including 5 feANP32A,3 feANP32B,and 2 feANP32E)were obtained from domestic cats by RT-PCR.Sequence alignment results demonstrated amino acid deletions and/or insertions occurred among feANP32 variants,but all feANP32 proteins were primarily localized to cell nucleus.Minigenome replication systems for several representative IAV strains were established and the support ability of feANP32 on IAV polymerase activity was estimated.The results indicated that most feANP32A and feANP32B splice variants were able to support all the tested IAV strains,though the support activity of a single feANP32 protein on polymerase activity varied among different IAV strains.In addition,the role of feANP32 in supporting H3N2 canine influenza virus was determined by investigating viral replication in vitro.Collectively,our study systematically investigated the support activity of feANP32 on IAV,providing a clue for further exploring the mechanism of susceptibility of cats to IAV.

Development and evaluation of a RT-RAA-combined CRISPR/Cas12a assay for the detection of African horse sickness virus

African horse sickness(AHS)is an acute and fatal vectorborne infectious disease of equids,caused by the African horse sickness virus(AHSV).The World Organization for Animal Health(WOAH)has classified AHS as a notifiable animal disease,and AHS has also been classified as a Class I animal infectious disease in China.AHS is mainly found in Africa,the Middle East and the Arabian Peninsula.China is currently recognized by the WOAH as an AHS-free zone.

Discovery of potent anti-MRSA components from Dalbergia odorifera through UPLC-Q-TOF-MS and targeting PBP2a protein through in-depth transcriptomic,in vitro,and in-silico studies

Methicillin-resistant Staphylococcus aureus(MRSA)is an important pathogen casting dire shadow over global human wellbeing[1].Rising antibiotic resistance in MRSA led to research into plant-derived anti-microbial agents.Approximately 119 compounds from 90 plants were recognized as potent anti-bacterials[2].Dalbergia odorifera,a traditional Chinese plant,has demonstrated anti-tumor,anti-microbial,anti-inflammatory,and cardiovascular protective effects[3].Limited studies have explored D.odorifera flavonoids'inhibitory activity against MRSA.Transcriptomics,a high-throughput method,aided in comprehending plant antibacterial therapy by generating data for gene expression,target identification,and pathway analysis[4].Consequently,our study aimed to assess D.odorifera's anti-MRSA effects and reveal its material foundation and antibacterial mechanism by ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS),and transcriptomic analysis,in vitro,and in-silico studies.

First identification of the oxazolidinone/phenicol resistance gene optrA in Streptococcus pluranimalium worldwide

Oxazolidinones are highly effective antimicrobial agents for the treatment of serious infections caused by Gram-positive organisms,including methicillin-resistant Staphylococcus aureus(MRSA),vancomycin-resistant enterococci(VRE),multidrug-resistant(MDR)pneumococci and MDR mycobacteria(Brenciani et al.2022).However,the emergence and prevalence of acquired oxazolidinone resistance genes.

A CRISPR/Cas12a-based platform for rapid on-site bovine viral diarrhea virus diagnostics

Bovine viral diarrhea virus(BVDV)is a positive-sense single-stranded RNA virus,belonging to the genus Pestivirus in the Flaviviridae family(Riitho et al.2020).Currently,BVDV is divided into 3 main genotypes,BVDV-1,BVDV-2,and BVDV-3,based on the genetic differences in the 5′untranslated region(5′UTR)(Muasya et al.2022).