Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus:A case report

BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.

Management of Strawberry Grey Mold Disease Using Biocontrol Agents and Plant Extracts

Strawberry (Fragaria × ananassa Duch.) is a significant global soft fruit crop, prized for its nutrient content and pleasant flavor. However, diseases, particularly grey mold caused by Botrytis cinerea Pers. Fr. poses major constraints to strawberry production and productivity. Grey mold severely impacts fruit quality and quantity, diminishing market value. This study evaluated five B. cinerea isolates from various locations in the Ri-Bhoi district of Meghalaya. All isolates were pathogenic, with isolate SGM 2 identified as highly virulent. Host range studies showed the pathogen-producing symptoms in the fava bean pods, marigold, gerbera, and chrysanthemum flowers and in the fava bean, gerbera, and lettuce leaves. In vitro tests revealed that neem extract (15% w/v) achieved the highest mycelial growth inhibition at 76.66%, while black turmeric extract (5% w/v) had the lowest inhibition at 9.62%. Dual culture methods with bio-control agents indicated that Bacillus subtilis recorded the highest mean inhibition at 77.03%, while Pseudomonas fluorescens had the lowest at 20.36% against the two virulent isolates. Pot evaluations demonstrated that B. subtilis resulted in the lowest percent disease index at 20.59%, followed by neem extract at 23.31%, with the highest disease index in the control group at 42.51%. Additionally, B. subtilis significantly improved plant growth, yielding an average of 0.32 kg compared to 0.14 kg in the control. The promising results of B. subtilis and neem leaf extract from this study suggest their potential for eco-friendly managing grey mold in strawberries under field conditions.

Disparities in the Levels of Whole-Blood Epstein-Barr Virus between the Cancer and Non-Cancer Populations in Zhejiang,China

Objective This study aimed to investigate the prevalence of Epstein-Barr virus(EBV)infection in patients with and without cancer.Methods A total of 26,648 participants who underwent whole-blood EBV DNA(WBEBV)assays between January 1,2020,and August 31,2023,were included.The chi-square test was used for categorical data analysis,and R software was used to analyze the differences in EBV DNA load levels and the diagnostic capabilities of WBEBV.Results Positive rates were 10.2%and 25.4%for healthy controls(HC)and patients,respectively.The positivity rate for EBV-associated neoplasms(EN)was the highest at 7.53%,followed by leukemia(Le)at 5.49%.The subgroup analysis showed that the positivity rate for abnormal proliferation or hyperplasia(APH)was 31.9%,followed by 30.5%for Le.The WBEBV of patients with transplants(TP),especially living-related transplants(LT),was the highest among all subgroups.WBEBV at diagnosis was used to differentiate between infectious mononucleosis(IM)and chronic active Epstein-Barr virus(CAEBV),with a sensitivity of 67.4%(95%confidence interval[CI]:57.6-75.8)and specificity of 72%(95%CI:63.3-79.3).We conclude that the prevalence of EBV infection is low in the healthy population in this region and that a high EBV load at baseline is more common in LT,IM,and Lymphocyte Leukemia(LL).Conclusion This study used a large-sample survey to characterize the prevalence of whole-blood EBV levels in various diseases,including the stages and subtypes.The EBV detection rate was higher in patients with malignant disease than in those with benign disease.Our study provides clinicians with baseline information regarding EBV-associated diseases.

Ellagic Acid Enhances Antioxidant System Activity and Maintains the Quality of Strawberry Fruit during Storage

Ellagic acid(EA)is a natural antioxidant,widely present in a lot of forms’soft fruits,nuts,and other plant tissues,and helpful for promoting human health;however,its protective effect on postharvest fruit and improving the quality index of postharvest fruit have rarely been studied.In this experiment,the strawberries were soaked in 0,100,200,300,400,and 500 mg L^(−1) EA,respectively,and the influential EA on fruit quality and the antioxidant system of strawberries were studied.Compared with the control,EA treatment can reduce the browning degree and rotting rate of strawberry fruit during storage and augment the soluble solid content(SSC).EA treatment can also increase the content of related stuff and enzyme activity in antioxidant systems;the gene expression level of polyphenol oxidase(PPO)in strawberries treated with EA was always down-regulated,correspondingly,the expression of other antioxidant enzyme genes was enhanced.Among the strawberry fruits treated with EA of different concentrations,300 mg L^(−1) EA had the best effect in the process of strawberry preservation.The results suggested that the proper concentration of exogenous EA at 300 mg L−1 could maintain strawberries’quality and enhance the antioxidant system by improving the activities of antioxidative enzymes and the ascorbateglutathione(AsA-GSH)cycle during storage.

Real-Time Detection and Instance Segmentation of Strawberry in Unstructured Environment

The real-time detection and instance segmentation of strawberries constitute fundamental components in the development of strawberry harvesting robots.Real-time identification of strawberries in an unstructured envi-ronment is a challenging task.Current instance segmentation algorithms for strawberries suffer from issues such as poor real-time performance and low accuracy.To this end,the present study proposes an Efficient YOLACT(E-YOLACT)algorithm for strawberry detection and segmentation based on the YOLACT framework.The key enhancements of the E-YOLACT encompass the development of a lightweight attention mechanism,pyramid squeeze shuffle attention(PSSA),for efficient feature extraction.Additionally,an attention-guided context-feature pyramid network(AC-FPN)is employed instead of FPN to optimize the architecture’s performance.Furthermore,a feature-enhanced model(FEM)is introduced to enhance the prediction head’s capabilities,while efficient fast non-maximum suppression(EF-NMS)is devised to improve non-maximum suppression.The experimental results demonstrate that the E-YOLACT achieves a Box-mAP and Mask-mAP of 77.9 and 76.6,respectively,on the custom dataset.Moreover,it exhibits an impressive category accuracy of 93.5%.Notably,the E-YOLACT also demonstrates a remarkable real-time detection capability with a speed of 34.8 FPS.The method proposed in this article presents an efficient approach for the vision system of a strawberry-picking robot.

CRISPR/CasRx-mediated resistance to Soybean mosaic virus in soybean

Soybean mosaic virus(SMV),an RNA virus,is the most common and destructive pathogenic virus in soybean fields.The newly developed CRISPR/Cas immune system has provided a novel strategy for improving plant resistance to viruses;hence,this study aimed to engineer SMV resistance in soybean using this system.Specifically,multiple sgRNAs were designed to target positive-and/or negative-sense strands of the SMV HC-Pro gene.Subsequently,the corresponding CRISPR/CasRx vectors were constructed and transformed into soybeans.After inoculation with SMV,39.02%,35.77%,and 18.70%of T_(1)plants were confirmed to be highly resistant(HR),resistant(R),and mildly resistant(MR)to SMV,respectively,whereas only 6.50%were identified as susceptible(S).Additionally,qRT-PCR and DAS-ELISA showed that,both at 15 and 30 d post-inoculation(dpi),SMV accumulation significantly decreased or was even undetectable in HR and R plants,followed by MR and S plants.Additionally,the expression level of the CasRx gene varied in almost all T_(1)plants with different resistance level,both at 15 and 30 dpi.Furthermore,when SMV resistance was evaluated in the T_(2)generation,the results were similar to those recorded for the T_(1)generation.These findings provide new insights into the application of the CRISPR/CasRx system for soybean improvement and offer a promising alternative strategy for breeding for resistance to biotic stress that will contribute to the development of SMV-immune soybean germplasm to accelerate progress towards greater soybean crop productivity.

FaSnRK1a mediates salicylic acid pathways to enhance strawberry resistance to Botrytis cinerea

Strawberry is a major fruit crop worldwide because its nutritional and health benefits to human health,but its productivity is limited by Botrytis cinerea.Sucrose nonfermentation 1-related protein kinase 1(SnRK1)has a defense function against pathogens,but the function of SnRK1 in the defense response to B.cinerea in plants is still unclear.In this study,FaSnRK1a-OE and RNAi fruits were constructed and then inoculated with B.cinerea.The result reveals a positive role of Fa SnRK1a in the regulation of resistance to gray mold.FaSnRK1a affects SA content by regulating FaPAL1 and FaPAL2 expressions.The genes related to the SA signaling pathway(FaTGA1 and FaTGA2.1)were significantly increased/decreased in FaSnRK1a-OE or FaSnRK1a-RNAi fruit,respectively.FaSnRK1a interacted with the FaWRKY33.2 protein and negatively regulated FaWRKY33.2 expression,and FaWRKY33.2 acts as a repressor of disease resistance to B.cinerea.Finally,FaSnRK1a regulates the expression of six PR genes and the activities of antioxidant enzymes to boost defense response after B.cinerea inoculation.Our findings showed that FaSnRK1a increases the resistance of strawberry fruit to B.cinerea via SA signaling pathway and interaction with the FaWRKY33.2 transcription factor.

Nipah Virus Unveiled: A Review Article

Nipah virus (NiV) is a highly infectious zoonotic pathogen that poses a significant threat to human and animal health. First identified in Malaysia in 1998, NiV has since caused several outbreaks in Southeast Asia, with sporadic cases reported in Bangladesh and India. The virus is primarily transmitted to humans through direct contact with infected animals, primarily fruit bats, or through the consumption of contaminated fruits and their juices. NiV infection presents a wide spectrum of clinical features, ranging from mild respiratory illness to severe encephalitis, with a high case fatality rate. The incubation period typically ranges from 4 to 14 days, during which patients develop fever, headache, myalgia, and respiratory symptoms such as cough and sore throat. As the disease progresses, neurological signs become prominent, including altered consciousness, seizures, and focal deficits. Severe cases may exhibit acute respiratory distress syndrome and multi organ failure. Laboratory findings often include lymphocytopenia, thrombocytopenia, and elevated liver enzymes. Diagnosis of NiV infection requires specialized laboratory testing, including reverse transcription-polymerase chain reaction (RT-PCR) and serological assays. Currently, no specific antiviral treatment exists for NiV infection, and management primarily focuses on supportive care. Prevention and control strategies encompass public health interventions, surveillance, and raising awareness among healthcare providers and the general population. The emergence and re-emergence of NiV highlight the urgent need for continued research, improved diagnostic capabilities, and the development of effective vaccines and therapeutics to mitigate the impact of this deadly virus.

Genome-Wide Discovery and Expression Profiling of the SWEET Sugar Transporter Gene Family in Woodland Strawberry (Fragaria vesca) under Developmental and Stress Conditions: Structural and Evolutionary Analysis

The SWEET(sugar will eventually be exported transporter)family proteins are a recently identified class of sugar transporters that are essential for various physiological processes.Although the functions of the SWEET proteins have been identified in a number of species,to date,there have been no reports of the functions of the SWEET genes in woodland strawberries(Fragaria vesca).In this study,we identified 15 genes that were highly homolo-gous to the A.thaliana AtSWEET genes and designated them as FvSWEET1–FvSWEET15.We then conducted a structural and evolutionary analysis of these 15 FvSWEET genes.The phylogenetic analysis enabled us to categor-ize the predicted 15 SWEET proteins into four distinct groups.We observed slight variations in the exon‒intron structures of these genes,while the motifs and domain structures remained highly conserved.Additionally,the developmental and biological stress expression profiles of the 15 FvSWEET genes were extracted and analyzed.Finally,WGCNA coexpression network analysis was run to search for possible interacting genes of FvSWEET genes.The results showed that the FvSWEET10 genes interacted with 20 other genes,playing roles in response to bacterial and fungal infections.The outcomes of this study provide insights into the further study of FvSWEET genes and may also aid in the functional characterization of the FvSWEET genes in woodland strawberries.

Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.

Epidemiological and Paraclinical Aspects of Helicobacter pylori Infection among Hepatitis B Virus Carriers in the Republic of Congo

Objective: Describe the epidemiological and paraclinical aspects of HP infection in hepatitis B virus carriers. Population and Method: This was a descriptive cross-sectional study running from January 1 to August 30, 2019, a period of 8 months. It took place in the Hospital Centers of the two major cities of Congo (Brazzaville and Pointe-Noire). The target population of our study consists of patients carrying HBV under antiviral treatment or not. Patients aged at least 18 years and consenting with a biological and morphological assessment were included. We did not include in our study patients taking or having taken antibiotics and/or PPIs less than 4 weeks ago. We excluded all patients who did not deposit fresh stools and those in whom stool extraction could not be done manually. The variables studied covered sociodemographic, clinical and paraclinical aspects. Data entry was done using Excel 8.0 software. Statistical analysis was carried out with SPSS 20.0 software. Results: During our study, we included 169 patients. The frequency of HPAG in the stools of HBV carriers in our study population was 63.9% (n = 109). Male patients represented 69% (n = 75) and female patients represented 31% (n = 34). The average age of the patients is 43.92 ± 13.51 years with extremes of 18 years and 80 years. Concerning profession, unemployed patients and those working in the private sector were the most represented in respectively 28.4% (n = 31) and 22.9% (n = 25) without statistical link. Households comprising between 4 - 10 people and the use of public latrines were the risk factors most represented in respectively 69% (n = 75) and 88% (n = 96) without statistical link. Clinically, hepatomegaly and signs of portal hypertension were most represented in 53% (n = 58) and 47% (n = 51). Biologically, HBV DNA was detectable in 60.5% of cases (n = 66).

Reactivation of hepatitis B virus infection – an important aspect of multifaceted problem

In this editorial we comment on the article published in the recent issue of the W orld Journal of Gastroenterology.We focus specifically on the problem of occult hepatitis B virus(HBV)infection,that is a result of previous hepatitis B(PHB)and a source for reactivation of HBV.The prevalence of PHB is underestimated due to the lack of population testing programs.However,this condition not only com-plicate anticancer treatment,but may be responsible for the development of other diseases,like cancer or autoimmune disorders.Here we unveil possible mecha-nisms responsible for realization of these processes and suggest practical approa-ches for diagnosis and treatment.

Effect of K Fertilizer on Absorption of Mineral Elements in Greenhouse-grown Strawberry Fruits

[Objectives]The paper was to explore the effect of K fertilizer on the absorption of mineral elements in greenhouse-grown strawberry fruits.[Methods]A systematic investigation was conducted on the effects of K fertilizer dosage levels on the absorption of mineral elements in Fengxiang strawberries,an excellent variety suitable for cultivation in Anhui Province.The investigation was carried out under medium N and P conditions in a greenhouse.[Results]The N content of strawberry fruits increased as the K_(2)O dosage increased within the range of 0-250 kg/hm^(2).Similarly,the P content of strawberry fruits increased gradually with the increase of K_(2)O dosage within the range of 0-125 kg/hm^(2).[Conclusions]This study presents a basis for enhancing the absorption of mineral elements in strawberry fruit by applying K appropriately.

Current updates on the epidemiology,pathogenesis and development of small molecule therapeutics for the treatment of Ebola virus infections

Ebola virus disease(EVD)is a rare,highly contagious and a deadly disease with a variable fatality rate ranging from 30%to 90%.Over the past two decades,Ebola pandemic has severely affected the sub-Sahara region including Democratic Republic of the Congo(DRC),and Uganda.The causative agents of the most EVD cases are three distinct species out of six Ebolaviruses namely Zaire Ebolavirus(ZEBOV),Sudan Ebolavirus(SUDV)and Bundibugyo Ebolavirus(BDBV).In recent years,significant strides have been made in therapeutic interventions.Notably,the US Food and Drug Administration has approved two monoclonal antibodies:InmazebTM(REGN-EB3)and Ansuvimab or EbangaTM.Additionally,many small molecules are currently in the developmental stage,promising further progress in medical treatment.Addressing the critical need for preventive measures,this review provides an in-depth analysis of the licensed Ebola vaccines-Ervebo and the combination of Zabdeno(Ad26.ZEBOV)and Mvabea(MVA-BN-Filo)as well as the vaccines which are currently being tested for their efficacy and safety in clinical studies.These vaccines might play an important role in curbing the spread and mitigating the impact of this lethal disease.The current treatment landscape for EVD encompasses both nutritional(supportive)and drug therapies.The review comprehensively details the origin,pathogenesis,and epidemiology of EVD,shedding light on the ongoing efforts to combat this devastating disease.It explores small molecules in various stages of the development,discusses patents filed or granted,and delves into the clinical and supportive therapies that form the cornerstone of EVD management.This review aims to provide the recent developments made in the design and synthesis of small molecules for scientific community to facilitate a deeper understanding of the disease and fostering the development of effective strategies for prevention,treatment,and control of EVD.

56 Years of the Marburg Virus—A Review of Therapeutics

Background: The Marburg virus (MARV) is the causative agent of Marburg virus disease (MVD). This filovirus first appeared in 1967 and has since caused several outbreaks with case fatality rates between 23% and 90%. The earliest cases of MVD are thought to be caused by exposure to an infected animal, either a reservoir host (some bat species, e.g., Rousettus aegyptiacus) or a spill-over host, such as non-human primates. The virus is spread between people by direct contact with blood or other bodily fluids (including saliva, sweat, faeces, urine, tears, and breast milk) from infected individuals. Despite the high fatality rate, the Marburg virus has no vaccine or drug treatment. Recent outbreaks of the virus in 2023 in Tanzania and Equatorial Guinea have reignited the need to develop effective therapeutics, especially in the wake of the COVID-19 pandemic. Purpose: This review seeks to highlight the drug discovery efforts aimed at developing vaccines or possible treatments as potential therapeutics. Several existing antiviral agents are being probed, and vaccines are in pre-clinical and clinical stages. Natural products are also an important source of possible drugs or lead compounds and when coupled with computational techniques, these strategies offer possible therapeutics for the Marburg virus, especially in Africa, which has a high disease burden. Methods: Using the search engines Google Scholar and PubMed;keywords e.g. Marburg virus, Marburg treatments, Marburg virus drug discovery were utilized. Several results were yielded, and articles published in recent years were accepted into the final list.Results and Conclusion: This study shows there is a growing interest in therapeutics for the Marburg virus, especially with the recent outbreaks and pandemic preparedness. Initiatives that to support vaccine development and access like the MARVAC consort time are critical to fighting this public health threat.

Development of a stable attenuated double-mutant of tobacco mosaic virus for cross-protection

Tobacco(Nicotiana tabacum)and tomato(Solanum lycopersicum)are two major economic crops in China.Tobacco mosaic virus(TMV;genus Tobamovirus)is the most prevalent virus infecting both crops.Currently,some widely cultivated tobacco and tomato cultivars are susceptible to TMV and there is no effective strategy to control this virus.Cross-protection can be a safe and environmentally friendly strategy to prevent viral diseases.However,stable attenuated TMV mutants are scarce.In this study,we found that the substitutions in the replicase p126,arginine at position 196(R^(196))with aspartic acid(D),glutamic acid at position 614(E^(614))with glycine(G),serine at position 643(S^(643))with phenylalanine(F),or D at position 730(D^(730))with S,significantly reduced the virulence and replication of TMV.However,only the mutation of S^(643) to F reduced the RNA silencing suppression activity of TMV p126.A double-mutant TMV-E614G-S643F induced no visible symptom and was genetically stable through six successive passages in tobacco plants.Furthermore,our results showed that TMV-E614G-S643F double-mutant could provide effective protection against the wild-type TMV infection in tobacco and tomato plants.This study reports a promising mild mutant for cross-protection to control TMV in tobacco and tomato plants.

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.