Research Advances in Infectious Mononucleosis Caused by Epstein-Barr Virus

Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), manifests as the classic triad of fever, pharyngitis, and cervical lymphadenopathy. Severe cases may involve organ damage, most commonly affecting the liver. Diagnosis relies on a combination of clinical presentation and laboratory parameters, with commonly used indicators including EBV-specific antibodies, EBV-DNA load, and the ratio of atypical lymphocytes. Treatment primarily involves symptomatic supportive care, with a cautious approach to the routine use of antiviral medications. In recent years, significant research in traditional Chinese medicine has been conducted in China, showing promising advancements. This article provides a comprehensive review of EBV-induced infectious mononucleosis, offering insights for clinical diagnosis and treatment.

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.

Characterization of the infectivity of an Indonesian Zika virus strain in mammalian cell lines

Objective:To characterize the infection patterns and growth characteristics of the Zika virus(ZIKV)strain JMB-185 from Indonesia in various mammalian cell lines.Methods:ZIKV was grown in human(A549,HEK293,HepG2,Huh7,Jurkat,and THP-1)and non-human mammalian(RAW264.7,Vero,and Vero76)cell lines.Viral replication kinetics were measured using plaque assay,while intra-and extracellular viral RNA concentrations were assessed using RT-PCR.Flow cytometry was used to quantify the infected cells and cell viability was measured using an MTT assay.The ability of ZIKV to infect cell lines was visualized using a fluorescence immunostaining assay.Results:This ZIKV strain preferentially infected the lung,kidney,and liver cell lines A549,HEK293,Huh7,Vero,and Vero76,but not the immune cells Jurkat,RAW264.7,and THP-1.By contrast,the ZIKV showed no sign of infection in HepG2 cells,while maintaining viral titer over 3 days post-infection,with no infection recorded in immunostaining,no increase in viral RNA,and no indication of cell deterioration.Conclusions:The Indonesian ZIKV strain has a similar infection profile as other strains,except for its poor infectivity on HepG2 cells.Information on the growth characteristics of Indonesia ZIKV will help expand our understanding of the biology of ZIKV which will be useful for various applications including antiviral discovery.

N6-methyladenosine methylation regulates the tumor microenvironment of Epstein-Barr virus-associated gastric cancer

BACKGROUND N6-methyladenosine(m6A)methylation modification exists in Epstein-Barr virus(EBV)primary infection,latency,and lytic reactivation.It also modifies EBV latent genes and lytic genes.EBV-associated gastric cancer(EBVaGC)is a distinctive molecular subtype of GC.We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC.AIM To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC.METHODS First,The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC(EBVnGC).Second,we identified Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment of m6A-related differentially expressed genes.We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment(TME).Finally,cell counting kit-8 cell proliferation test,transwell test,and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1(IGFBP1)in EBVaGC cell lines.RESULTS m6A methylation regulators were involved in the occurrence and development of EBVaGC.Compared with EBVnGC,the expression levels of m6A methylation regulators Wilms tumor 1-associated protein,RNA binding motif protein 15B,CBL proto-oncogene like 1,leucine rich pentatricopeptide repeat containing,heterogeneous nuclear ribonucleoprotein A2B1,IGFBP1,and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC(P<0.05).The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher(P=0.046).GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC.Compared with EBVnGC,the infiltration of activated CD4+T cells,activated CD8+T cells,monocytes,activated dendritic cells,and plasmacytoid dendritic cells were significantly upregulated in EBVaGC(P<0.001).In EBVaGC,the expression level of proinflammatory factors interleukin(IL)-17,IL-21,and interferon-γ and immunosuppressive factor IL-10 were significantly increased(P<0.05).In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line(SNU719)than in an EBVnGC cell line(AGS)(P<0.05).IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719.Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS.CONCLUSION m6A regulators could remodel the TME of EBVaGC,which is classified as an immune-inflamed phenotype and referred to as a“hot”tumor.Among these regulators,we demonstrated that IGFBP1 affected proliferation,migration,and apoptosis.

Perception of Medical Students towards Hepatitis B Virus Infection and Hepatitis B Vaccination in a Private Tertiary Hospital in Jos North Local Government, Plateau State, Nigeria

Background: Prevention is one of the safe schemes against the high prevalence of viral Hepatitis. Negative perceptions or perceptions about the risks of hepatitis B among medical students and health care workers may influence the behavioral pattern and adoption of preventive measures against the virus and can affect the uptake of the Hepatitis B vaccine. This study assesses the perception of medical students towards Hepatitis B virus infection and Hepatitis B Vaccination in a Private Tertiary Hospital in Jos North Local Government, Plateau State, Nigeria. Methods: This was a descriptive cross-sectional study done in August 2021 among 236 clinical medical students using a multistage sampling technique. Data was collected using an interviewer-administered structured questionnaire and analysed using the IBM SPSS 28 (Statistical Package for the Social Sciences). Ethical approval was granted by Bingham University Teaching Hospital, Ethics Committee, Jos, Plateau State. Results: Two-thirds of respondents were of the opinion that they are at risk of contracting HBV. Half were of the opinion that the risk is very much while a third believed the risk is moderate. Among those who think they are not at risk of contracting HBV, the majority felt so because they are vaccinated while 10.3% believe that they are safe. 43.2% of respondents think that HBV Vaccine is very effective in preventing HBV infection while 39.8% think it is slightly effective, and 7.6% think it is not effective. Almost all respondents, 99.2% are of the opinion that HBV Vaccination is important for students while 0.8% think it is not important. The majority of the respondents at 95.8% were willing to be screened for HBV. The majority (85.6%) of respondents are willing to pay for HBV Vaccine as against 14.4% of respondents who are not willing to pay. Conclusion: Summarily, 21 (8.9%) of the students had a negative perception of Hepatitis B Vaccination, and 215 (91.1%) had a positive perception of Hepatitis B Vaccination. Perception-sustaining events like seminars, workshops, road shows, and campaigns should be organized among students and health workers.

Analysis of Occurrence and Mixed Infection of Sugarcane Bacilliform Virus Disease in Hainan Sugarcane-growing Area

[Objectives]The paper was to explore the occurrence and mixed infection of sugarcane bacilliform virus disease in Hainan sugarcane-growing area.[Methods]A total of 348 sugarcane leaf samples were collected from 7 sugarcane-growing areas in Hainan Province.Molecular detection of sugarcane bacilliform virus(SCBV)was carried out by PCR using specific primers.[Results]SCBV was detected in 244 out of 348 sugarcane samples,with an average detection rate of 70.11%.The highest detection rate was 76.66%in the Danzhou sugarcane-growing area,while the lowest was 57.14%in the Baisha sugarcane-growing area.The SCBV-positive samples were subjected to testing for SCYLV,SCSMV,SrMV,and SCMV,respectively.The results indicated that 106 out of 244 positive samples exhibited a single infection with SCBV,while 138 samples exhibited mixed infections with SCBV and other sugarcane viruses.The proportion of mixed infections among the SCBV-positive samples was as high as 56.56%.Among the various types of mixed infections,two-virus and three-virus mixed infections were the most prevalent.[Conclusions]SCBV has emerged as a significant threat to the secure production of sugarcane in the Hainan sugarcane-growing region.It presents an explosive infection in the Hainan sugarcane-growing region and frequently combines with other sugarcane viruses to infect sugarcane.The findings of this study will provide a theoretical foundation for the prevention and control of sugarcane bacilliform virus disease.

Positive correlation between latent Epstein-Barr virus infection and severity of illness in inflammatory bowel disease patients

BACKGROUND Emerging studies indicate the critical involvement of microorganisms,such as Epstein-Barr virus(EBV),in the pathogenesis of inflammatory bowel disease(IBD).Immunosuppressive therapies for IBD can reactivate latent EBV,complicating the clinical course of IBD.Moreover,the clinical significance of EBV expression in B lymphocytes derived from IBD patients’intestinal tissues has not been explored in detail.AIM To explore the clinical significance of latent EBV infection in IBD patients.METHODS Latent EBV infection was determined by double staining for EBV encoded RNA and CD20 in colon specimens of 43 IBD patients who underwent bowel resection.Based on the staining results,the patients were divided into two groups,according to their latent EBV infection states-negative(n=33)and positive(n=10).Illness severity of IBD were assigned according to Crohn’s disease activity index(ulcerative colitis)and Mayo staging system(Crohn’s disease).The clinicpathological data were analyzed between the two different latent EBV groups and also between the mild-to-moderate and severe disease groups.RESULTS Systolic pressure(P=0.005),variety of disease(P=0.005),the severity of illness(P=0.002),and pre-op corticosteroids(P=0.025)were significantly different between the EBV-negative and EBV-positive groups.Systolic pressure(P=0.001),variety of disease(P=0.000),pre-op corticosteroids(P=0.011)and EBV infection(P=0.003)were significantly different between the mild-to-moderate and severe disease groups.CONCLUSION IBD patients with latent EBV infection may manifest more severe illnesses.It is suggested that the role of EBV in IBD development should be further investigated,latent EBV infection in patients with serious IBD should be closely monitored,and therapeutic course should be optimized.

Epstein-Barr virus-induced infection-associated hemophagocytic lymphohistiocytosis with acute liver injury:A case report

BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a severe hyperinflammatory reaction,which is rare and life-threatening.According to the pathogen,HLH is divided into genetic and acquired.The most common form of acquired HLH is infection-associated HLH,of which Herpes viruses,particularly Epstein-Barr virus(EBV),are the leading infectious triggers.However,it is difficult to distinguish between simple infection with EBV and EBV-induced infectionassociated HLH since both can destroy the whole-body system,particularly the liver,thereby increasing the difficulty of diagnosis and treatment.CASE SUMMARY This paper elaborates a case about EBV-induced infection-associated HLH and acute liver injury,aiming to propose clinical guides for the early detection and treatment of patients with EBV-induced infection-associated HLH.The patient was categorized as acquired hemophagocytic syndrome in adults.After the ganciclovir antiviral treatment combined with meropenem antibacterial therapy and methylprednisolone inhibition to inflammatory response,gamma globulin enhanced immunotherapy,the patient recovered.CONCLUSION From the diagnosis and treatment of this patient,attention should be paid to routine EBV detection and a further comprehensive understanding of the disease as well as early recognition and early initiation are keys to patients’survival.

Emerging perspectives on RNA virus-mediated infections:from pathogenesis to therapeutic interventions

RNA viruses continue to pose significant threats to global public health,necessitating a profound understanding of their pathogenic mechanisms and the development of effective therapeutic interventions.This manuscript provides a comprehensive overview of emerging perspectives on RNA virus-mediated infections,spanning from the intricate intricacies of viral pathogenesis to the forefront of innovative therapeutic strategies.A critical exploration of antiviral drugs sets the stage,highlighting the diverse classes of compounds that target various stages of the viral life cycle,underscoring the ongoing efforts to combat viral infections.Central to this discussion is the exploration of RNA-based therapeutics,with a spotlight on messenger RNA(mRNA)-based approaches that have revolutionized the landscape of antiviral interventions.Furthermore,the manuscript delves into the intricate world of delivery systems,exploring innovative technologies designed to enhance the efficiency and safety of mRNA vaccines.By analyzing the challenges and advancements in delivery mechanisms,this review offers a roadmap for future research and development in this critical area.Beyond conventional infectious diseases,the document explores the expanding applications of mRNA vaccines,including their promising roles in cancer immunotherapy and personalized medicine approaches.This manuscript serves as a valuable resource for researchers,clinicians,and policymakers alike,offering a nuanced perspective on RNA virus pathogenesis and the cutting-edge therapeutic interventions.By synthesizing the latest advancements and challenges,this review contributes significantly to the ongoing discourse in the field,driving the development of novel strategies to combat RNA virus-mediated infections effectively.

Management strategies for common viral infections in pediatric renal transplant recipients

Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.

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.

Demyelinating neuropathy in patients with hepatitis B virus: A case report

BACKGROUND Hepatitis B rarely leads to demyelinating neuropathy,despite peripheral neuropathy being the first symptom of hepatitis B infection.CASE SUMMARY A 64-year-old man presented with sensorimotor symptoms in multiple peripheral nerves.Serological testing showed that these symptoms were due to hepatitis B.After undergoing treatment involving intravenous immunoglobulin and an antiviral agent,there was a notable improvement in his symptoms.CONCLUSION Although hepatitis B virus(HBV)infection is known to affect hepatocytes,it is crucial to recognize the range of additional manifestations linked to this infection.The connection between long-term HBV infection and demyelinating neuropathy has seldom been documented;hence,prompt diagnostic and treatment are essential.The patient's positive reaction to immunoglobulin seems to be associated with production of the antigen-antibody immune complex.

Hepatitis B virus reactivation in patients treated with monoclonal antibodies

Hepatitis B virus(HBV)reactivation poses a significant clinical challenge,espe-cially in patients undergoing immunosuppressive therapies,including mono-clonal antibody treatments.This manuscript briefly explores the complex rela-tionship between monoclonal antibody therapy and HBV reactivation,drawing upon current literature and clinical case studies.It delves into the mechanisms underlying this phenomenon,highlighting the importance of risk assessment,monitoring,and prophylactic measures for patients at risk.The manuscript aims to enhance the understanding of HBV reactivation in the context of monoclonal antibody therapy,ultimately facilitating informed clinical decision-making and improved patient care.This paper will also briefly review the definition of HBV activation,assess the risks of reactivation,especially in patients treated with monoclonal antibodies,and consider management for patients with regard to screening,prophylaxis,and treatment.A better understanding of patients at risk can help clinicians provide optimum management to ensure successful patient outcomes and prevent morbidity.

Transcriptome analysis reveals different response of resistant and susceptible rice varieties to rice stripe virus infection

Rice stripe disease,caused by rice stripe virus (RSV) which is transmitted by small brown planthopper (SBPH,Laodelphax striatellus Fallen),resulted in serious losses to rice production during the last 2 decades.Research on the molecular differences between resistant and susceptible rice varieties and the interaction between rice and RSV remains inadequate.In this study,RNA-Seq was used to analyze the transcriptomic differences between the resistant and susceptible rice varieties at different times post RSV infection.Through Gene Ontology (GO) annotation,the differentially expressed genes (DEGs) related to transcription factors,peroxidases,and kinases of 2 varieties at 3 time points were identified.Comparing these 2 varieties,the DEGs associated with these 3 GOs were numerically less in the resistant variety than in the susceptible variety,but the expression showed a significant up-or down-regulation trend under the conditions of|log_2(Fold change)|>0&P_(adj)<0.05 by significance analysis.Then through Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation,DEGs involved in some pathways that have a contribution to disease resistance including plant hormone signal transduction and plant–pathogen interaction were found.The results showed that resistance responses regulated by abscisic acid (ABA) and brassinosteroids (BR) were the same for 2 varieties,but that mediated by salicylic acid (SA) and jasmonic acid (JA)/ethylene (ET) were different.The DEGs in resistant and susceptible varieties at the 3 time points were identified in both PAMP-triggered immunity (PTI) and Effector proteintriggered immunity (ETI),with that most of the unigenes of the susceptible variety were involved in PTI,whereas most of the unigenes of the resistant variety were involved in ETI.These results revealed the different responses of resistant and susceptible varieties in the transcription level to RSV infection.

Hepatitis B virus infection in patients with Wilson disease:A large retrospective study

BACKGROUND Wilson disease(WD)is the most common genetic metabolic liver disease.Some studies have shown that comorbidities may have important effects on WD.Data on hepatitis B virus(HBV)infection in patients with WD are limited.AIM To investigate the prevalence and clinical impact of HBV infection in patients with WD.METHODS The clinical data of patients with WD were analyzed retrospectively,and the data of patients with concurrent WD and HBV infection were compared with those of patients with isolated WD.RESULTS Among a total of 915 WD patients recruited,the total prevalence of current and previous HBV infection was 2.1%[95%confidence interval(CI):1.2%-3.0%]and 9.2%(95%CI:7.3%-11.1%),respectively.The main finding of this study was the identification of 19 patients with concurrent WD and chronic hepatitis B(CHB)infection.The diagnosis of WD was missed in all but two patients with CHB infection.The mean delay in the diagnosis of WD in patients with concurrent WD and CHB infection was 32.5 mo,which was significantly longer than that in patients with isolated WD(10.5 mo).The rates of severe liver disease and mortality in patients with concurrent WD and CHB infection were significantly higher than those in patients with isolated WD(63.1%vs 19.3%,P=0.000 and 36.8%vs 4.1%,P<0.001,respectively).Binary logistic regression analysis revealed a significantly higher risk of severe liver disease at the diagnosis of WD in patients with current HBV infection[odds ratio(OR)=7.748;95%CI:2.890-20.774;P=0.000)]or previous HBV infection(OR=5.525;95%CI:3.159-8.739;P=0.000)than in patients with isolated WD.CONCLUSION The total prevalence of current HBV infection in patients with WD was 2.1%.The diagnosis of WD in CHB patients is usually missed.HBV infection is an independent risk factor for severe liver disease in WD patients.The diagnosis of WD should be ruled out in some patients with CHB infection.

Serological diagnosis of Epstein-Barr virus infection: Problems and solutions

Serological tests for antibodies specific for Epstein-Barr virus(EBV) antigens are frequently used to define infection status and for the differential diagnosis of other pathogens responsible for mononucleosis syndrome. Using only three parameters [viral capsid antigen(VCA) Ig G, VCA Ig M and EBV nuclear antigen(EBNA)-1 Ig G],it is normally possible to distinguish acute from past infection: the presence of VCA Ig M and VCA Ig G without EBNA-1 Ig G indicates acute infection, whereas the presence of VCA Ig G and EBNA-1 Ig G without VCA Ig M is typical of past infection. However, serological findings may sometimes be difficult to interpret as VCA Ig G can be present without VCA Ig M or EBNA-1 Ig G in cases of acute or past infection, or all the three parameters may be detected simultaneously in the case of recent infection or during the course of reactivation. A profile of isolated EBNA-1 Ig G may also create some doubts. In order to interpret these patterns correctly, it is necessary to determine Ig G avidity, identify anti-EBV Ig G and Ig M antibodies by immunoblotting, and look for heterophile antibodies, anti-EA(D) antibodies or viral genome using molecular biology methods. These tests make it possible to define the status of the infection and solve any problems that may arise in routine laboratory practice.

What's new in hepatitis C virus infections in children?

The number of hepatitis C virus(HCV) infection cases is relatively low in children. This low number may be connected with the lack of screening tests and the asymptomatic course of infection. Currently,mother-toinfant transmission is the most common cause of HCV infection amongst children in developed countries. It is important to introduce routine screening tests for HCV in pregnant women. The risk of vertical transmission of HCV is estimated at approximately 5%(3%-10%). Currently,we do not have HCV transmission prevention methods. Some factors could potentially be eliminated by elective caesarean section. Currently,the method of prevention of perinatal HCV infection is the early identification and effective treatment of infections in young women in the preconception period. We describe genetic tests(IL-28 B single nucleotide polymorphisms) to identify children with an increased chance of spontaneous clearance or sustained virologic response achievement and vitamin D level as a potential predictor of treatment response in children. It is also important to develop non-invasive tests that can predict liver fibrosis. The existence of differences in the mechanisms leading to liver injury between children and adults creates new perspectives of action to reduce liver disease progression in children in the early years of life.

Co-infection of Epstein-Barr virus and human papillomavirus in human tumorigenesis

Viral infections contribute to approximately 12%of cancers worldwide,with the vast majority occurring in developing countries and areas.Two DNA viruses,Epstein-Barr virus(EBV) and human papillomavirus(HPV),are associated with38%of all virus-associated cancers.The probability of one patient infected with these two distinct types of viruses is increasing.Here,we summarize the co-infection of EBV and HPV in human malignancies and address the possible mechanisms for the co-infection of EBV and HPV during tumorigenesis.

Development of Epstein-Barr virus-associated gastric cancer:Infection,inflammation,and oncogenesis

Epstein-Barr virus(EBV)-associated gastric cancer(EBVaGC)cells originate from a single-cell clone infected with EBV.However,more than 95%of patients with gastric cancer have a history of Helicobacter pylori(H.pylori)infection,and H.pylori is a major causative agent of gastric cancer.Therefore,it has long been argued that H.pylori infection may affect the development of EBVaGC,a subtype of gastric cancer.Atrophic gastrointestinal inflammation,a symptom of H.pylori infection,is observed in the gastric mucosa of EBVaGC.Therefore,it remains unclear whether H.pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H.pylori and EBV infections act independently on gastric cancer formation.It has been reported that EBV infection assists in the oncogenesis of gastric cancer caused by H.pylori infection.In contrast,several studies have reported that H.pylori infection accelerates tumorigenesis initiated by EBV infection.By reviewing both clinical epidemiological and experimental data,we reorganized the role of H.pylori and EBV infections in gastric cancer formation.

Heterochronic triple primary malignancies with Epstein-Barr virus infection and tumor protein 53 gene mutation:A case report and review of literature

BACKGROUND The diagnosis and etiology of multiple primary malignant neoplasms(MPMNs)are difficult to establish.Here,we report a case of heterochronic triple primary malignancies with gastric cancer,nasopharyngeal squamous cell cancer,and then rectal cancer.CASE SUMMARY The patient was first diagnosed with gastric cancer at the age of 33 in 2014 and underwent distal gastrectomy and gastrojejunostomy and six cycles of adjuvant chemotherapy.Three years later,he was diagnosed with nasopharyngeal cancer and treated with radical chemoradiotherapy in 2017.Recently,a mass in the middle of the rectum was resected and reported as ulcerative,moderately to poorly differentiated adenocarcinoma.Research on the etiology of MPMNs showed that Epstein-Barr virus(EBV)infection may be the cause of gastric cancer and nasopharyngeal squamous cell cancer since these two primary lesions were positive for transcripts of EBV-encoded ribonucleic acid using an in situ hybridization EBV-encoded ribonucleic acid probe in formalin-fixed,paraffinembedded tissue.The cause of rectal cancer may be due to a somatic mutation of tumor protein 53 gene in exon 8(c.844C>T,p.Arg282Trp)through highthroughput sequencing for the rectal cancer.Appropriate standard therapy for each primary cancer was administered,and the patient has no evidence of cancer disease to date.CONCLUSION To our knowledge,this is the first report on heterochronic triple primary malignancies whose cause may be associated with EBV infection and tumor protein 53 genetic mutations.The etiological research may not only elucidate the cause of MPMN but also has implications in clinical management.