Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegment...Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegmented RNA genome.Due to its high pathogenicity and lethality,LASV is considered as a priority threat to public health,with an estimated cases of 300,000 infections and 5000 deaths annually.LASV was first isolated and described as a clinical entity in 1969 in Lassa,Nigeria(Garry,2023).LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages,with each lineage predominately localized in specific countries.Although the research on LF has been carried out for decades since the pathogen first characterized,there is no approved antiviral drugs or vaccines for clinical use against LASV to date(Grant et al.,2023).One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4(BSL-4)facilities.In this letter,we describe isolation,and characterization of the LASV from the clinical samples.And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility,aiming to investigate new therapeutic strategies for LASV infection.展开更多
The 2024 development of a precision-engineered retrotransposon system marked a significant milestone in mammalian genome-editing research.As appeared in the July 8 issue of Cell,this methodological breakthrough establ...The 2024 development of a precision-engineered retrotransposon system marked a significant milestone in mammalian genome-editing research.As appeared in the July 8 issue of Cell,this methodological breakthrough established a novel framework for site-specific gene delivery through repurposing ancient viral tools.展开更多
Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global populat...Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global population has been infected with HEV.There are an estimated 20 million new cases of HEV infection worldwide annually.World Health Organization(WHO)reported that HEV caused approximately 44000 deaths in 2015,which accounted for3.3%of deaths from viral hepatitis[3,4].Clinically,most cases of acute hepatitis E have a self-limiting course.However,co-infection with other viruses can increase the risk of acute or subacute liver failure.Hepatitis B virus(HBV)and HEV are highly prevalent in many regions worldwide,and these areas have high rates of coinfection with both viruses.The rate of co-infection with HEV among patients with chronic hepatitis B(CHB)is high,resulting in more severe health outcomes and a significantly elevated risk of liver failure and death.展开更多
Influenza A viruses(IAVs)are single-stranded negative-sense RNA viruses that continually challenge animal and human health.In IAV-infected cells,host RNA-binding proteins play key roles in the life cycle of IAV by dir...Influenza A viruses(IAVs)are single-stranded negative-sense RNA viruses that continually challenge animal and human health.In IAV-infected cells,host RNA-binding proteins play key roles in the life cycle of IAV by directly binding to viral RNA.Here,we examined the role of the host RNA-binding protein nucleophosmin-1(NPM1)in IAV replication.We found that,as a nucleolar phosphoprotein,NPM1 directly binds to viral RNA(vRNA)and inhibits the replication of various subtypes of IAV.NPM1 binding to vRNA competitively reduces the assembly of the viral ribonucleoprotein complex and the viral polymerase activity,thereby reducing the generation of progeny viral RNA and virions.The RNA-binding activity of NPM1,with the key residues T199,T219,T234,and T237,is essential for its anti-influenza function.Taken together,our findings demonstrate that NPM1 acts as an RNA-binding protein and interacts with IAV vRNA to suppress viral replication.展开更多
Sickle cell disease(SCD)is a genetic disorder that predisposes affected individuals to a range of complications,including an increased susceptibility to viral infections.These infections present significant clinical c...Sickle cell disease(SCD)is a genetic disorder that predisposes affected individuals to a range of complications,including an increased susceptibility to viral infections.These infections present significant clinical challenges due to the underlying immunocompromised state in SCD patients.This review examines the interaction between viral infections and SCD,highlighting the vulnerabilities and the impact of these infections on morbidity and mortality in this population.Advances in antiviral therapies have significantly improved outcomes,yet managing viral infections in SCD patients requires special consideration due to drug-to-drug interactions,altered pharmacokinetics,and the potential exacerbation of SCDrelated complications.Additionally,vaccination strategies against viral infections and the emerging role of prophylactic antiviral treatments are discussed as critical components of infection prevention.By focusing on both established and novel antiviral treatments,this article aims to provide a comprehensive overview of the challenges and opportunities in managing viral infections in patients with SCD.展开更多
BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients followi...BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients following long-term antiviral treatment.However,in the absence of imaging evidence of liver cancer,a reasonable expla-nation for this phenomenon is still lacking.AIM To explore the causes of abnormal AFP in patients with CHB who were not diag-nosed with liver cancer.METHODS From November 2019 to May 2023,15 patients with CHB after antiviral treatment and elevated AFP were selected.Clinical data and quality indicators related to laboratory testing,imaging data,and pathological data were obtained through inpatient medical records.RESULTS All patients had increased AFP and significantly elevated IgG.Cancer was excluded by imaging examination.Only four patients had elevated alanine ami-notransferase,10 had elevated aspartate aminotransferase,nine had elevated total bilirubin,and two had antinuclear antibodies.The liver biopsy and histopatho-logical examination indicated that 14 patients had rosette,moderate,or higher interfacial inflammation,lymphocyte infiltration,and severe hepatic fibers(11 cases),which was consistent with the pathological features of autoimmune hepa-titis(AIH).After 8-12 week of hormone therapy,the levels of AFP and IgG,and liver function returned to normal(P<0.05).CONCLUSION For patients with CHB and elevated AFP after antiviral treatment,autoimmune hepatitis should be considered.CHB with AIH is clinically insidious and difficult to detect,and prone to progression to cirrhosis.Liver puncture pathological examination should be performed when necessary to confirm diagnosis.展开更多
Rift Valley fever virus(RVFV)is a high-containment pathogen that causes severe diseases in humans,with no approved therapeutics available.Its classification as a biosafety level 3(BSL-3)agent has limited research and ...Rift Valley fever virus(RVFV)is a high-containment pathogen that causes severe diseases in humans,with no approved therapeutics available.Its classification as a biosafety level 3(BSL-3)agent has limited research and therapeutic development due to safety concerns.In this study,we developed a stable replicon cell line maintaining the replication of L and S genomic segments of RVFV.Single-cycle viral replicon particles(VRPs)could be efficiently packaged through trans-complementation of glycoproteins from different strains,recapitulating authentic viral entry and replication while minimizing biosafety risks.Using this system,we conducted high-throughput screening of a small-molecule compound library and identified CNX-1351 as an antiviral agent for multiple RNA viruses.Mechanistic studies revealed that CNX-1351 inhibits viral replication,potentially by targeting the PI3K-Akt signaling pathway.This single-cycle VRP system provides a valuable tool for studying RVFV biology,host interactions,antiviral and vaccine development under reduced biosafety constraints.展开更多
Viral infectious diseases,characterized by their intricate nature and wide-ranging diversity,pose substantial challenges in the domain of data management.The vast volume of data generated by these diseases,spanning fr...Viral infectious diseases,characterized by their intricate nature and wide-ranging diversity,pose substantial challenges in the domain of data management.The vast volume of data generated by these diseases,spanning from the molecular mechanisms within cells to large-scale epidemiological patterns,has surpassed the capabilities of traditional analytical methods.In the era of artificial intelligence(AI)and big data,there is an urgent necessity for the optimization of these analytical methods to more effectively handle and utilize the information.Despite the rapid accumulation of data associated with viral infections,the lack of a comprehensive framework for integrating,selecting,and analyzing these datasets has left numerous researchers uncertain about which data to select,how to access it,and how to utilize it most effectively in their research.This review endeavors to fill these gaps by exploring the multifaceted nature of viral infectious diseases and summarizing relevant data across multiple levels,from the molecular details of pathogens to broad epidemiological trends.The scope extends from the micro-scale to the macro-scale,encompassing pathogens,hosts,and vectors.In addition to data summarization,this review thoroughly investigates various dataset sources.It also traces the historical evolution of data collection in the field of viral infectious diseases,highlighting the progress achieved over time.Simultaneously,it evaluates the current limitations that impede data utilization.Furthermore,we propose strategies to surmount these challenges,focusing on the development and application of advanced computational techniques,AI-driven models,and enhanced data integration practices.By providing a comprehensive synthesis of existing knowledge,this review is designed to guide future research and contribute to more informed approaches in the surveillance,prevention,and control of viral infectious diseases,particularly within the context of the expanding big-data landscape.展开更多
The aim of this study was to assess the seroprevalence of viral hepatitis B and C and co-infection with HIV among volunteer blood donors at the blood sampling and distribution depot (BSDD) in Ouahigouya. Patients and ...The aim of this study was to assess the seroprevalence of viral hepatitis B and C and co-infection with HIV among volunteer blood donors at the blood sampling and distribution depot (BSDD) in Ouahigouya. Patients and methods: Our study population consisted of all volunteer blood donors who had donated during a 2-year period from 1 January 2019 to 31 December 2020. Samples were taken from patients with no contraindications and serological tests were performed using ELISA tests. HBsAg, HCV-Ac and HIV serology were tested. All samples reactive for HIV, HBV and HCV were retested for confirmation using a second enzyme-linked immunosorbent assay. A result was considered positive if both the first and second tests were positive. Results: In two years, the Ouahigouya BSDD recorded 9726 donations, including 7983 new donors and 1743 former donors. The average age of donors was 25.59 years, with a sex ratio of 3.4. The seroprevalence of HBV, HCV and HIV was 7.31%, 3.10% and 2.12% respectively. HBV-HCV co-infection was found in 0.32% of cases, HIV-HBV, HIV-HCV, and HIV-HBV-HCV co-infection were found in 0.25%, 0.09% and 0.04% respectively. Conclusion: The seroprevalence of viral hepatitis B and C remains high among volunteer blood donors in Ouahigouya, although a decline in seroprevalence appears to be on the horizon.展开更多
Aim: To describe electrical and echocardiographic abnormalities in patients with viral cirrhosis B. Methodology: Prospective cross-sectional study with an analytical aim carried out in the hospitalization and outpatie...Aim: To describe electrical and echocardiographic abnormalities in patients with viral cirrhosis B. Methodology: Prospective cross-sectional study with an analytical aim carried out in the hospitalization and outpatient departments of the Hepato-Gastroenterology department and in the emergency department of the Cocody University Hospital during the period from January 15 to July 15, 2022. Any patient with viral B cirrhosis and having performed an echocardiography and an electrocardiogram was included. The significance threshold was stopped at p Results: 40 patients were selected. The prevalence of viral B cirrhosis was 16.8% and that of cirrhotic cardiomyopathy in cirrhotic patients was 33.9%. The average age of the patients was 43.9 ± 14.1. There was a male predominance with a sex ratio of 3.4. The two main clinical signs found in patients were ascites (77.5%) and edema (75%). There was a lowering of TP (70%), albumin (72.5%) and platelets (87.5%). Bilirubin was elevated in 60% of patients. All patients had a liver with irregular contours. 80% of our population had not performed Fibroscan®, 5% had fibrosis between F3-F4 and 35% F4 fibrosis. The main complication found was portal hypertension (esophageal varices at any stage) at 85%. Cirrhosis was active (virological) in 32.5% of patients. 75% of patients were classified as Child B. The two main abnormalities on echocardiography were left ventricular hypertrophy (32.5%) and dilatation of the left atrium (7.5%). The electrical abnormalities found were mainly QT prolongation (32.5%) and sinus tachycardia (12.5%). We did not find a statistically significant association between the severity of cirrhosis and electrical abnormalities. There was a statistically significant association between the severity of cirrhosis and the dilation of the left atrium (p = 0.04). Conclusion: Cirrhotic cardiomyopathy is a rare complication of cirrhosis.展开更多
Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacter...Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacterial interactions,molecular responses,and therapeutic approaches,the mortality rate associated with sepsis has consistently ranged between 10%and 16%.This elevated mortality highlights critical gaps in our comprehension of sepsis etiology.Traditionally linked to bacterial and fungal pathogens,recent outbreaks of acute viral infections,including Middle East respiratory syndrome coronavirus(MERS-CoV),influenza virus,and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),among other regional epidemics,have underscored the role of viral pathogenesis in sepsis,particularly when critically ill patients exhibit classic symptoms indicative of sepsis.However,many cases of viral-induced sepsis are frequently underdiagnosed because standard evaluations typically exclude viral panels.Moreover,these viruses not only activate conventional pattern recognition receptors(PRRs)and retinoic acid-inducible gene-I(RIG-I)-like receptors(RLRs)but also initiate primary antiviral pathways such as cyclic guanosine monophosphate adenosine monophosphate(GMP-AMP)synthase(cGAS)-stimulator of interferon genes(STING)signaling and interferon response mechanisms.Such activations lead to cellular stress,metabolic disturbances,and extensive cell damage that exacerbate tissue injury while leading to a spectrum of clinical manifestations.This complexity poses substantial challenges for the clinical management of affected cases.In this review,we elucidate the definition and diagnosis criteria for viral sepsis while synthesizing current knowledge regarding its etiology,epidemiology,and pathophysiology,molecular mechanisms involved therein as well as their impact on immune-mediated organ damage.Additionally,we discuss clinical considerations related to both existing therapies and advanced treatment interventions,aiming to enhance the comprehensive understanding surrounding viral sepsis.展开更多
The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates ...The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.展开更多
There are limited biosecurity measures directed at preventing airborne transmission of viruses in swine.The effectiveness of dust mitigation strategies such as oil sprinkling,to decrease risk of airborne virus transmi...There are limited biosecurity measures directed at preventing airborne transmission of viruses in swine.The effectiveness of dust mitigation strategies such as oil sprinkling,to decrease risk of airborne virus transmission are unknown.Metagenomics and qPCR for common fecal viruses were used to hunt for a ubiquitous virus to serve as a proxy when evaluating the efficiency of mitigation strategies against airborne viral infectious agents.Air particles were collected from swine buildings using high-volume air samplers.Extracted DNA and RNA were used to perform specific RT-qPCR and qPCR and analyzed by highthroughput sequencing.Porcine astroviruses group 2 were common(from 102 to 105 genomic copies per cubic meter of air or gc/m^(3),93%positivity)while no norovirus genogroup II was recovered from air samples.Porcine torque teno sus virus were detected by qPCR in low concentrations(from 101 to 102 gc/m^(3),47%positivity).Among the identified viral families by metagenomics analysis,Herelleviridae,Microviridae,Myoviridae,Podoviridae,and Siphoviridae were dominant.The phage vB_AviM_AVP of Aerococcus was present in all air samples and a newly designed qPCR revealed between 101 and 105 gc/m^(3) among the samples taken for the present study(97%positivity)and banked samples from5-and 15-year old studies(89%positivity).According to the present study,both the porcine astrovirus group 2 and the phage vB_AviM_AVP of Aerococcus could be proxy for airborne viruses of swine buildings.展开更多
Viral hepatitis,including hepatitis B and hepatitis C(HCV),remains a significant global health burden,leading to liver fibrosis,cirrhosis,and hepatocellular car-cinoma.Traditional diagnostic methods,while effective,of...Viral hepatitis,including hepatitis B and hepatitis C(HCV),remains a significant global health burden,leading to liver fibrosis,cirrhosis,and hepatocellular car-cinoma.Traditional diagnostic methods,while effective,often face limitations in accuracy,accessibility,and timeliness.Artificial intelligence(AI)has emerged as a transformative tool in healthcare,enhancing the detection,diagnosis,and treat-ment of viral hepatitis.This review explores the role of AI in viral hepatitis mana-gement,focusing on early detection through image analysis,digital pathology,and machine learning algorithms.AI-driven image analysis tools,such as con-volutional neural networks,have demonstrated high accuracy in detecting HCV-related liver lesions from computed tomography scans.Supervised learning models such as support vector machines and hybrid quantum neural networks further enhance early risk stratification.AI also facilitates personalized treatment by predicting treatment responses,accelerating drug discovery,and advancing precision medicine.Furthermore,AI contributes to epidemiological surveillance by predicting disease spread and tracking treatment adherence.Despite its po-tential,challenges such as data privacy,algorithmic bias,and regulatory comp-liance must be addressed to ensure equitable and effective AI implementation.Future directions include integrating AI into clinical workflows and expanding AI applications in low-resource settings.AI-assisted diagnosis and management have the potential to revolutionize viral hepatitis care,improving patient outcomes and reducing the global disease burden.展开更多
In rice fields,rice plants usually grow alongside wild weeds and are attacked by various invertebrate species.Viruses are abundant in plants and invertebrates,playing crucial ecological roles in controlling microbial ...In rice fields,rice plants usually grow alongside wild weeds and are attacked by various invertebrate species.Viruses are abundant in plants and invertebrates,playing crucial ecological roles in controlling microbial abundance and maintaining community structures.To date,only 16 rice viruses have been documented in rice-growing regions.These viruses pose serious threats to rice production and have traditionally been identified only from rice plants and insect vectors by isolation techniques.Advances in next-generation sequencing(NGS)have made it feasible to discover viruses on a global scale.Recently,numerous viruses have been identified in plants and invertebrates using NGS technologies.In this review,we discuss viral studies in rice plants,invertebrate species,and weeds in rice fields.Many novel viruses have been discovered in rice ecosystems through NGS technologies,with some also detected using metatranscriptomic and small RNA sequencing.These analyses greatly expand our understanding of viruses in rice fields and provide valuable insights for developing efficient strategies to manage insect pests and virus-mediated rice diseases.展开更多
Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy.The oncolytic influenza A virus,although promising in preclinical investigations,remains to be implemented in clinical practice.Recent prog...Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy.The oncolytic influenza A virus,although promising in preclinical investigations,remains to be implemented in clinical practice.Recent progress in genetic engineering,coupled with experiential insights,offers opportunities to enhance the therapeutic efficacy of the influenza A virus.This review explores the use of the influenza virus,its attenuated forms,and associated vaccines in cancer immunotherapy,highlighting their respective advantages and challenges.We further elucidate methods for engineering influenza viruses and innovative approaches to augment them with cytokines or immune checkpoint inhibitors,aiming to maximize their clinical impact.Our goal is to provide insights essential for refining influenza A virus-based viral tumor immunotherapies.展开更多
The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function,...The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.展开更多
Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis.Management of myocarditis is primarily supportive,because there are currently no established targeted therapies.Recent ...Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis.Management of myocarditis is primarily supportive,because there are currently no established targeted therapies.Recent studies have increasingly highlighted the association between the gut microbiota and myocarditis.Here,we report a case of acute severe ulcerative colitis complicated by cytomegalovirus and Epstein-Barr virus co-infections that led to viral myocarditis.The patient experienced rapid remission of both intestinal and cardiac symptoms following washed microbiota transplantation,suggesting this intervention may serve as a potential alternative treatment for these life-threatening conditions.展开更多
Pseudoalteromonas is a group of marine bacteria widespread in diverse marine sediments,producing a wide range of bioactive compounds.However,only a limited number of Pseudoalteromonas phages have been isolated and stu...Pseudoalteromonas is a group of marine bacteria widespread in diverse marine sediments,producing a wide range of bioactive compounds.However,only a limited number of Pseudoalteromonas phages have been isolated and studied.In this study,a novel lytic Pseudoalteromonas phage,denoted as vB_PalP_Y7,was isolated from sewage samples collected at the Seafood Market in Qingdao,China.vB_PalP_Y7 remained stable across a wide range of temperatures(-20–50℃)and a wide pH range(3–12).The vB_PalP_Y7 phage harbors a linear double-stranded DNA molecule of 57699 base pairs(bp)with a G+C content of 45.90%.Furthermore,it is predicted to contain 58 open reading frames(ORFs).Phylogenetic analysis and protein network relationship analysis revealed low similarity between vB_PalP_Y7 and viruses in the ICTV and IMG/VR4 database,suggesting that vB_PalP_Y7 may be a potential new genus,Miuvirus.This study contributed valuable insights to comprehend the relationship between Pseudoalteromonas phages and their host organisms.展开更多
BACKGROUND Viral hepatitis is characterized by a group of hepatotropic viruses that contribute to high rates of liver disease and mortality.It is well-documented that viral hepatitis is the leading cause of liver canc...BACKGROUND Viral hepatitis is characterized by a group of hepatotropic viruses that contribute to high rates of liver disease and mortality.It is well-documented that viral hepatitis is the leading cause of liver cancer and liver failure,with Hepatitis B and Hepatitis C being the most common viruses associated with these outcomes.AIM To study viral hepatitis-related mortality trends from 1999 to 2022,focusing on gender,race/ethnicity,age,region,and urban/rural classifications.METHODS We used the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database to identify viral hepatitis-related deaths in the United States from 1999 to 2022.Data on demographic and regional information were analyzed and stratified by gender,race/ethnicity,age,regional,and urban rural classifications.Using the Joinpoint Regression Program(version 4.9.0.0 used,available from the National Cancer Institute,Bethesda,Maryland)the annual percentage change(APC)and average APC(AAPC)were calculated with 95%CI for extracted Age Adjusted Mortality Rates(AAMR).RESULTS From 1999 to 2022,there were 389916 viral hepatitis-related deaths in the United States.The overall AAMR increased from 1999 to 2013(APC:3.20%;95%CI:2.54-3.99;P<0.001),then declined through 2022(APC:-5.54%;95%CI:-6.75 to-4.47;P<0.001).Males accounted for 70.4%of deaths,with steeper declines in females(AAPC:-0.48%;95%CI:-0.87 to-0.12;P<0.05).The American Indian/Alaska Native population had the highest AAMR(AAPC:2.90%;95%CI:2.30 to 3.68;P<0.001).The population of 65-74 years had the largest increase in overall crude mortality rate(AAPC:3.20%;95%CI:2.77 to 3.85;P<0.001).Mortality was highest in the West(AAPC:-0.78%;95%CI-1.28 to-0.29;P<0.05).Rural AAMR exceeded urban rates after 2015.CONCLUSION This study found significant racial,ethnic,and geographical disparities in viral hepatitis AAMR.Key factors for mortality reduction include patient education,screening,and access to hepatitis vaccination and treatment.展开更多
基金supported by the National Key Research and Development Program of China(2022YFC2303300,2023YFC2605504)the National Natural Science Foundation of China(82172273 and 31670165)the Open Research Fund Program of the State Key Laboratory of Virology of China(2023JZZD-01).
文摘Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegmented RNA genome.Due to its high pathogenicity and lethality,LASV is considered as a priority threat to public health,with an estimated cases of 300,000 infections and 5000 deaths annually.LASV was first isolated and described as a clinical entity in 1969 in Lassa,Nigeria(Garry,2023).LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages,with each lineage predominately localized in specific countries.Although the research on LF has been carried out for decades since the pathogen first characterized,there is no approved antiviral drugs or vaccines for clinical use against LASV to date(Grant et al.,2023).One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4(BSL-4)facilities.In this letter,we describe isolation,and characterization of the LASV from the clinical samples.And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility,aiming to investigate new therapeutic strategies for LASV infection.
文摘The 2024 development of a precision-engineered retrotransposon system marked a significant milestone in mammalian genome-editing research.As appeared in the July 8 issue of Cell,this methodological breakthrough established a novel framework for site-specific gene delivery through repurposing ancient viral tools.
基金supported by a grant from the Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project(2019ZB101)。
文摘Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global population has been infected with HEV.There are an estimated 20 million new cases of HEV infection worldwide annually.World Health Organization(WHO)reported that HEV caused approximately 44000 deaths in 2015,which accounted for3.3%of deaths from viral hepatitis[3,4].Clinically,most cases of acute hepatitis E have a self-limiting course.However,co-infection with other viruses can increase the risk of acute or subacute liver failure.Hepatitis B virus(HBV)and HEV are highly prevalent in many regions worldwide,and these areas have high rates of coinfection with both viruses.The rate of co-infection with HEV among patients with chronic hepatitis B(CHB)is high,resulting in more severe health outcomes and a significantly elevated risk of liver failure and death.
基金supported by funding from the National Natural Science Foundation of China(U23A20243 and 32272972 to QZ,32172820 to SX)the Major Science and Technology Project of Gansu Province(22ZD6NA001 to SX)+1 种基金the Youth Innovation Program(Y2023QC30)the Agricultural Science and Technology Innovation Program(CAAS-ASTIP-JBGS-20210102 to SX)of the Chinese Academy of Agricultural Sciences.
文摘Influenza A viruses(IAVs)are single-stranded negative-sense RNA viruses that continually challenge animal and human health.In IAV-infected cells,host RNA-binding proteins play key roles in the life cycle of IAV by directly binding to viral RNA.Here,we examined the role of the host RNA-binding protein nucleophosmin-1(NPM1)in IAV replication.We found that,as a nucleolar phosphoprotein,NPM1 directly binds to viral RNA(vRNA)and inhibits the replication of various subtypes of IAV.NPM1 binding to vRNA competitively reduces the assembly of the viral ribonucleoprotein complex and the viral polymerase activity,thereby reducing the generation of progeny viral RNA and virions.The RNA-binding activity of NPM1,with the key residues T199,T219,T234,and T237,is essential for its anti-influenza function.Taken together,our findings demonstrate that NPM1 acts as an RNA-binding protein and interacts with IAV vRNA to suppress viral replication.
文摘Sickle cell disease(SCD)is a genetic disorder that predisposes affected individuals to a range of complications,including an increased susceptibility to viral infections.These infections present significant clinical challenges due to the underlying immunocompromised state in SCD patients.This review examines the interaction between viral infections and SCD,highlighting the vulnerabilities and the impact of these infections on morbidity and mortality in this population.Advances in antiviral therapies have significantly improved outcomes,yet managing viral infections in SCD patients requires special consideration due to drug-to-drug interactions,altered pharmacokinetics,and the potential exacerbation of SCDrelated complications.Additionally,vaccination strategies against viral infections and the emerging role of prophylactic antiviral treatments are discussed as critical components of infection prevention.By focusing on both established and novel antiviral treatments,this article aims to provide a comprehensive overview of the challenges and opportunities in managing viral infections in patients with SCD.
文摘BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients following long-term antiviral treatment.However,in the absence of imaging evidence of liver cancer,a reasonable expla-nation for this phenomenon is still lacking.AIM To explore the causes of abnormal AFP in patients with CHB who were not diag-nosed with liver cancer.METHODS From November 2019 to May 2023,15 patients with CHB after antiviral treatment and elevated AFP were selected.Clinical data and quality indicators related to laboratory testing,imaging data,and pathological data were obtained through inpatient medical records.RESULTS All patients had increased AFP and significantly elevated IgG.Cancer was excluded by imaging examination.Only four patients had elevated alanine ami-notransferase,10 had elevated aspartate aminotransferase,nine had elevated total bilirubin,and two had antinuclear antibodies.The liver biopsy and histopatho-logical examination indicated that 14 patients had rosette,moderate,or higher interfacial inflammation,lymphocyte infiltration,and severe hepatic fibers(11 cases),which was consistent with the pathological features of autoimmune hepa-titis(AIH).After 8-12 week of hormone therapy,the levels of AFP and IgG,and liver function returned to normal(P<0.05).CONCLUSION For patients with CHB and elevated AFP after antiviral treatment,autoimmune hepatitis should be considered.CHB with AIH is clinically insidious and difficult to detect,and prone to progression to cirrhosis.Liver puncture pathological examination should be performed when necessary to confirm diagnosis.
基金Grants from the Program of Shanghai Academic Research Leader(22XD1420600)Shanghai Municipal Science and Technology Major Project(ZD2021CY001)+2 种基金National Natural Science Foundation of China(81974305)Shenzhen Medical Research Fund(SMRF No.B2302029)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-02)supported this work.
文摘Rift Valley fever virus(RVFV)is a high-containment pathogen that causes severe diseases in humans,with no approved therapeutics available.Its classification as a biosafety level 3(BSL-3)agent has limited research and therapeutic development due to safety concerns.In this study,we developed a stable replicon cell line maintaining the replication of L and S genomic segments of RVFV.Single-cycle viral replicon particles(VRPs)could be efficiently packaged through trans-complementation of glycoproteins from different strains,recapitulating authentic viral entry and replication while minimizing biosafety risks.Using this system,we conducted high-throughput screening of a small-molecule compound library and identified CNX-1351 as an antiviral agent for multiple RNA viruses.Mechanistic studies revealed that CNX-1351 inhibits viral replication,potentially by targeting the PI3K-Akt signaling pathway.This single-cycle VRP system provides a valuable tool for studying RVFV biology,host interactions,antiviral and vaccine development under reduced biosafety constraints.
基金supported by the National Natural Science Foundation of China(32370703)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M-1-021,2021-I2M-1-061)the Major Project of Guangzhou National Labora-tory(GZNL2024A01015).
文摘Viral infectious diseases,characterized by their intricate nature and wide-ranging diversity,pose substantial challenges in the domain of data management.The vast volume of data generated by these diseases,spanning from the molecular mechanisms within cells to large-scale epidemiological patterns,has surpassed the capabilities of traditional analytical methods.In the era of artificial intelligence(AI)and big data,there is an urgent necessity for the optimization of these analytical methods to more effectively handle and utilize the information.Despite the rapid accumulation of data associated with viral infections,the lack of a comprehensive framework for integrating,selecting,and analyzing these datasets has left numerous researchers uncertain about which data to select,how to access it,and how to utilize it most effectively in their research.This review endeavors to fill these gaps by exploring the multifaceted nature of viral infectious diseases and summarizing relevant data across multiple levels,from the molecular details of pathogens to broad epidemiological trends.The scope extends from the micro-scale to the macro-scale,encompassing pathogens,hosts,and vectors.In addition to data summarization,this review thoroughly investigates various dataset sources.It also traces the historical evolution of data collection in the field of viral infectious diseases,highlighting the progress achieved over time.Simultaneously,it evaluates the current limitations that impede data utilization.Furthermore,we propose strategies to surmount these challenges,focusing on the development and application of advanced computational techniques,AI-driven models,and enhanced data integration practices.By providing a comprehensive synthesis of existing knowledge,this review is designed to guide future research and contribute to more informed approaches in the surveillance,prevention,and control of viral infectious diseases,particularly within the context of the expanding big-data landscape.
文摘The aim of this study was to assess the seroprevalence of viral hepatitis B and C and co-infection with HIV among volunteer blood donors at the blood sampling and distribution depot (BSDD) in Ouahigouya. Patients and methods: Our study population consisted of all volunteer blood donors who had donated during a 2-year period from 1 January 2019 to 31 December 2020. Samples were taken from patients with no contraindications and serological tests were performed using ELISA tests. HBsAg, HCV-Ac and HIV serology were tested. All samples reactive for HIV, HBV and HCV were retested for confirmation using a second enzyme-linked immunosorbent assay. A result was considered positive if both the first and second tests were positive. Results: In two years, the Ouahigouya BSDD recorded 9726 donations, including 7983 new donors and 1743 former donors. The average age of donors was 25.59 years, with a sex ratio of 3.4. The seroprevalence of HBV, HCV and HIV was 7.31%, 3.10% and 2.12% respectively. HBV-HCV co-infection was found in 0.32% of cases, HIV-HBV, HIV-HCV, and HIV-HBV-HCV co-infection were found in 0.25%, 0.09% and 0.04% respectively. Conclusion: The seroprevalence of viral hepatitis B and C remains high among volunteer blood donors in Ouahigouya, although a decline in seroprevalence appears to be on the horizon.
文摘Aim: To describe electrical and echocardiographic abnormalities in patients with viral cirrhosis B. Methodology: Prospective cross-sectional study with an analytical aim carried out in the hospitalization and outpatient departments of the Hepato-Gastroenterology department and in the emergency department of the Cocody University Hospital during the period from January 15 to July 15, 2022. Any patient with viral B cirrhosis and having performed an echocardiography and an electrocardiogram was included. The significance threshold was stopped at p Results: 40 patients were selected. The prevalence of viral B cirrhosis was 16.8% and that of cirrhotic cardiomyopathy in cirrhotic patients was 33.9%. The average age of the patients was 43.9 ± 14.1. There was a male predominance with a sex ratio of 3.4. The two main clinical signs found in patients were ascites (77.5%) and edema (75%). There was a lowering of TP (70%), albumin (72.5%) and platelets (87.5%). Bilirubin was elevated in 60% of patients. All patients had a liver with irregular contours. 80% of our population had not performed Fibroscan®, 5% had fibrosis between F3-F4 and 35% F4 fibrosis. The main complication found was portal hypertension (esophageal varices at any stage) at 85%. Cirrhosis was active (virological) in 32.5% of patients. 75% of patients were classified as Child B. The two main abnormalities on echocardiography were left ventricular hypertrophy (32.5%) and dilatation of the left atrium (7.5%). The electrical abnormalities found were mainly QT prolongation (32.5%) and sinus tachycardia (12.5%). We did not find a statistically significant association between the severity of cirrhosis and electrical abnormalities. There was a statistically significant association between the severity of cirrhosis and the dilation of the left atrium (p = 0.04). Conclusion: Cirrhotic cardiomyopathy is a rare complication of cirrhosis.
基金supported by the National Natural Science Foundation of China(82372176,82272217,82002026,81971818)the Hubei Provincial Key Research and Development Program of China(2023BCB091)the National Key Research and Development Program of China(2021YFC2500802,2021YFC2300200).
文摘Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacterial interactions,molecular responses,and therapeutic approaches,the mortality rate associated with sepsis has consistently ranged between 10%and 16%.This elevated mortality highlights critical gaps in our comprehension of sepsis etiology.Traditionally linked to bacterial and fungal pathogens,recent outbreaks of acute viral infections,including Middle East respiratory syndrome coronavirus(MERS-CoV),influenza virus,and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),among other regional epidemics,have underscored the role of viral pathogenesis in sepsis,particularly when critically ill patients exhibit classic symptoms indicative of sepsis.However,many cases of viral-induced sepsis are frequently underdiagnosed because standard evaluations typically exclude viral panels.Moreover,these viruses not only activate conventional pattern recognition receptors(PRRs)and retinoic acid-inducible gene-I(RIG-I)-like receptors(RLRs)but also initiate primary antiviral pathways such as cyclic guanosine monophosphate adenosine monophosphate(GMP-AMP)synthase(cGAS)-stimulator of interferon genes(STING)signaling and interferon response mechanisms.Such activations lead to cellular stress,metabolic disturbances,and extensive cell damage that exacerbate tissue injury while leading to a spectrum of clinical manifestations.This complexity poses substantial challenges for the clinical management of affected cases.In this review,we elucidate the definition and diagnosis criteria for viral sepsis while synthesizing current knowledge regarding its etiology,epidemiology,and pathophysiology,molecular mechanisms involved therein as well as their impact on immune-mediated organ damage.Additionally,we discuss clinical considerations related to both existing therapies and advanced treatment interventions,aiming to enhance the comprehensive understanding surrounding viral sepsis.
基金supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research+1 种基金by CiberNed Intramural Collaborative Projects(ref.PI2020/09)by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
文摘The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
文摘There are limited biosecurity measures directed at preventing airborne transmission of viruses in swine.The effectiveness of dust mitigation strategies such as oil sprinkling,to decrease risk of airborne virus transmission are unknown.Metagenomics and qPCR for common fecal viruses were used to hunt for a ubiquitous virus to serve as a proxy when evaluating the efficiency of mitigation strategies against airborne viral infectious agents.Air particles were collected from swine buildings using high-volume air samplers.Extracted DNA and RNA were used to perform specific RT-qPCR and qPCR and analyzed by highthroughput sequencing.Porcine astroviruses group 2 were common(from 102 to 105 genomic copies per cubic meter of air or gc/m^(3),93%positivity)while no norovirus genogroup II was recovered from air samples.Porcine torque teno sus virus were detected by qPCR in low concentrations(from 101 to 102 gc/m^(3),47%positivity).Among the identified viral families by metagenomics analysis,Herelleviridae,Microviridae,Myoviridae,Podoviridae,and Siphoviridae were dominant.The phage vB_AviM_AVP of Aerococcus was present in all air samples and a newly designed qPCR revealed between 101 and 105 gc/m^(3) among the samples taken for the present study(97%positivity)and banked samples from5-and 15-year old studies(89%positivity).According to the present study,both the porcine astrovirus group 2 and the phage vB_AviM_AVP of Aerococcus could be proxy for airborne viruses of swine buildings.
文摘Viral hepatitis,including hepatitis B and hepatitis C(HCV),remains a significant global health burden,leading to liver fibrosis,cirrhosis,and hepatocellular car-cinoma.Traditional diagnostic methods,while effective,often face limitations in accuracy,accessibility,and timeliness.Artificial intelligence(AI)has emerged as a transformative tool in healthcare,enhancing the detection,diagnosis,and treat-ment of viral hepatitis.This review explores the role of AI in viral hepatitis mana-gement,focusing on early detection through image analysis,digital pathology,and machine learning algorithms.AI-driven image analysis tools,such as con-volutional neural networks,have demonstrated high accuracy in detecting HCV-related liver lesions from computed tomography scans.Supervised learning models such as support vector machines and hybrid quantum neural networks further enhance early risk stratification.AI also facilitates personalized treatment by predicting treatment responses,accelerating drug discovery,and advancing precision medicine.Furthermore,AI contributes to epidemiological surveillance by predicting disease spread and tracking treatment adherence.Despite its po-tential,challenges such as data privacy,algorithmic bias,and regulatory comp-liance must be addressed to ensure equitable and effective AI implementation.Future directions include integrating AI into clinical workflows and expanding AI applications in low-resource settings.AI-assisted diagnosis and management have the potential to revolutionize viral hepatitis care,improving patient outcomes and reducing the global disease burden.
基金supported by the National Natural Science Foundation of China(Grant Nos.31972983 and 32072487)the Key Technology R&D Program of Zhejiang Province,China(Grant No.2021C02006)the Zhejiang Provincial Natural Science Foundation of China(Grant No.LY23C140001).
文摘In rice fields,rice plants usually grow alongside wild weeds and are attacked by various invertebrate species.Viruses are abundant in plants and invertebrates,playing crucial ecological roles in controlling microbial abundance and maintaining community structures.To date,only 16 rice viruses have been documented in rice-growing regions.These viruses pose serious threats to rice production and have traditionally been identified only from rice plants and insect vectors by isolation techniques.Advances in next-generation sequencing(NGS)have made it feasible to discover viruses on a global scale.Recently,numerous viruses have been identified in plants and invertebrates using NGS technologies.In this review,we discuss viral studies in rice plants,invertebrate species,and weeds in rice fields.Many novel viruses have been discovered in rice ecosystems through NGS technologies,with some also detected using metatranscriptomic and small RNA sequencing.These analyses greatly expand our understanding of viruses in rice fields and provide valuable insights for developing efficient strategies to manage insect pests and virus-mediated rice diseases.
基金supported by the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(No.2022R01002)the National Natural Science Foundation of China(Nos.82272300 and 82102893)the Fundamental Research Funds for the Central Universities(No.226-2024-00062),China.
文摘Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy.The oncolytic influenza A virus,although promising in preclinical investigations,remains to be implemented in clinical practice.Recent progress in genetic engineering,coupled with experiential insights,offers opportunities to enhance the therapeutic efficacy of the influenza A virus.This review explores the use of the influenza virus,its attenuated forms,and associated vaccines in cancer immunotherapy,highlighting their respective advantages and challenges.We further elucidate methods for engineering influenza viruses and innovative approaches to augment them with cytokines or immune checkpoint inhibitors,aiming to maximize their clinical impact.Our goal is to provide insights essential for refining influenza A virus-based viral tumor immunotherapies.
基金supported by the National Natural Science Foundation of China(grant no.82370015).
文摘The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.
文摘Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis.Management of myocarditis is primarily supportive,because there are currently no established targeted therapies.Recent studies have increasingly highlighted the association between the gut microbiota and myocarditis.Here,we report a case of acute severe ulcerative colitis complicated by cytomegalovirus and Epstein-Barr virus co-infections that led to viral myocarditis.The patient experienced rapid remission of both intestinal and cardiac symptoms following washed microbiota transplantation,suggesting this intervention may serve as a potential alternative treatment for these life-threatening conditions.
基金the National Natural Science Foundation of China(Nos.42188102,42120104006,41976117,42176111)the Fundamental Research Funds for the Central Universities(Nos.202172002,201812002)the funding from Andrew Mc Minn。
文摘Pseudoalteromonas is a group of marine bacteria widespread in diverse marine sediments,producing a wide range of bioactive compounds.However,only a limited number of Pseudoalteromonas phages have been isolated and studied.In this study,a novel lytic Pseudoalteromonas phage,denoted as vB_PalP_Y7,was isolated from sewage samples collected at the Seafood Market in Qingdao,China.vB_PalP_Y7 remained stable across a wide range of temperatures(-20–50℃)and a wide pH range(3–12).The vB_PalP_Y7 phage harbors a linear double-stranded DNA molecule of 57699 base pairs(bp)with a G+C content of 45.90%.Furthermore,it is predicted to contain 58 open reading frames(ORFs).Phylogenetic analysis and protein network relationship analysis revealed low similarity between vB_PalP_Y7 and viruses in the ICTV and IMG/VR4 database,suggesting that vB_PalP_Y7 may be a potential new genus,Miuvirus.This study contributed valuable insights to comprehend the relationship between Pseudoalteromonas phages and their host organisms.
文摘BACKGROUND Viral hepatitis is characterized by a group of hepatotropic viruses that contribute to high rates of liver disease and mortality.It is well-documented that viral hepatitis is the leading cause of liver cancer and liver failure,with Hepatitis B and Hepatitis C being the most common viruses associated with these outcomes.AIM To study viral hepatitis-related mortality trends from 1999 to 2022,focusing on gender,race/ethnicity,age,region,and urban/rural classifications.METHODS We used the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database to identify viral hepatitis-related deaths in the United States from 1999 to 2022.Data on demographic and regional information were analyzed and stratified by gender,race/ethnicity,age,regional,and urban rural classifications.Using the Joinpoint Regression Program(version 4.9.0.0 used,available from the National Cancer Institute,Bethesda,Maryland)the annual percentage change(APC)and average APC(AAPC)were calculated with 95%CI for extracted Age Adjusted Mortality Rates(AAMR).RESULTS From 1999 to 2022,there were 389916 viral hepatitis-related deaths in the United States.The overall AAMR increased from 1999 to 2013(APC:3.20%;95%CI:2.54-3.99;P<0.001),then declined through 2022(APC:-5.54%;95%CI:-6.75 to-4.47;P<0.001).Males accounted for 70.4%of deaths,with steeper declines in females(AAPC:-0.48%;95%CI:-0.87 to-0.12;P<0.05).The American Indian/Alaska Native population had the highest AAMR(AAPC:2.90%;95%CI:2.30 to 3.68;P<0.001).The population of 65-74 years had the largest increase in overall crude mortality rate(AAPC:3.20%;95%CI:2.77 to 3.85;P<0.001).Mortality was highest in the West(AAPC:-0.78%;95%CI-1.28 to-0.29;P<0.05).Rural AAMR exceeded urban rates after 2015.CONCLUSION This study found significant racial,ethnic,and geographical disparities in viral hepatitis AAMR.Key factors for mortality reduction include patient education,screening,and access to hepatitis vaccination and treatment.
