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.

Partial Fusion (F) Gene Analysis of Newcastle Disease Virus Detected in Pakistan during 2021-2022

Newcastle disease (ND) virus is a leading threat to commercial and domestic poultry in Pakistan. The virus infects and constitutes irreversible impairment to the nervous system, damages the respiratory system, and marks severe gastrointestinal lesions leading to heavy mortality in short-living birds and substantial losses in layers and breeders. The continuous emergence and evolution of the virus made it inclined to evade the humoral response and indirectly the circumvention of artificial active immunization. Newcastle disease is caused by the orthoavula genus of the paramyxoviridae family and has shown high genetic diversity even in their genotypes while information regarding enzootic trends of the virus is scanty in Pakistan. A total of 40 tracheal samples of NDV were collected from different commercial broiler farms and 11 isolates of NDV were identified. In the current study, we determined the genetic diversity of the Newcastle disease virus based on the partial sequencing of the fusion protein gene available in the NCBI database. Genetic analysis showed that seven isolates belonged to class I genotype VII and four belonged to class II genotype II. Interestingly, two isolates had epidemiological connections with vaccine-like class II genotype II. Our findings, concerning the recent outbreaks of class I genotype VII and class II genotype II of NDV in vaccinated commercial flocks, suggest possible potential partial mutations in the fusion protein gene. Genetic diversity and formation of the new cleavage site in an important neutralizing protein of wild strain are linked with the potency of artificial active immunization and a major cause of vaccine failure.

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.

Cloning and Prokaryotic Expression of VP1 Gene of Foot-and-Mouth Disease Virus (FMDV) Type O

According to the complete genome of foot-and-mouth disease virus(FMDV)type O,a pair of special primers was designed to amplify VP1 gene.The VP1 gene was amplified by RT-PCR and subsequently inserted into the expression vector pGEX-6p-1 and induced by IPTG.Then SDS-PAGE showed the expressed protein was 51 kD in molecular weight.Then the product was purified by GSTrap FF columns.The product was detected through Western-blot that showed the protein has antigenicity.It provided fundamental data and materials for further investigation on diagnosis method of FMDV.

Genomic Sequencing and Molecular Characteristics of A Very Virulent Strain of Infectious Bursal Disease Virus Isolated in China

[Objective] The paper was to determine the genomic sequence of a very virulent strain of infectious bursal disease virus（IBDV）,and study its molecular characteristics.[Method] A very virulent strain（vvIBDV）（HLJ-0504） of infectious bursal disease virus（IBDV） with special characters was isolated in China and its genome was sequenced.[Result] Sequence analysis showed that segment A of HLJ-0504 was derived from vvIBDV,while segment B was from a distinct ancestor.The morbidity and mortality of HLJ-0504 was 100% and 86.7%to SPF chickens,respectively.[Conclusion] vvIBDV with distinct segment B were still circulating and the evolution of IBDV was diversified in China.Besides,it is hard to imagine that the virulence of IBDV is determined solely by segment A or B.

Screening of Anti-Newcastle Disease Virus Ingredients of Phyllanthus urinaria

[ Objective ] The aim of the study was to screen the antiviral ingredients of Chinese herbal medicine Phyllanthus urinaria in order to devel- op new drugs for the treatment of viral diseases of poultry. [ Method ] The whole grass of phyllanthus was respectively decocted in 75% ethanol （E） and pure water （PF）, and then the active ingredients were separately extracted in petroleum ether （PE）, ethyl acetate （EA）, and n-butyl alcohol （BU）. The extracts were inoculated on chicken embryo fibroblast （CEF） to observe their inhibitory effect on cytopathic effect （CPE） of Newcastle disease virus （NDV）, inoculated into chicken embryos to observe the changes of the hemagglutination titer of NDV, and inoculated in chickens to determine the mortality and evaluate their effect of immune protection. [ Result] The E -PE and E -BU extracts, especially E -BU extract, inhibi- ted CPE of NDV on CEF and significantly inhibited the proliferation of NDV in chicken embryo （P〈0.05） ; the survival rate of E-PE and E-BU group was extremely significantly higher than that of ribavirin group and the normal saline control （ P 〈0.01 ）, with E - PE group more higher. [ Condusion] The water extract of phyllanthus is less effective; E -PE extract and E -BU extract should effectively inhibit the CPE and proliferation in chicken embryo of NDV and also have better immune protection against NDV.

Genetic Analysis of the VP2 Hypervariable Region of Thirty-six Infectious Bursal Disease Virus Isolates in China during 2009-2012

[Objective] Infectious bursal disease （IBD） is a highly contagious immuno- suppressive disease caused by infectious bursal disease virus （IBDV）. IBDV is ge- netically prone to mutation, which results in challenges to the disease prevention and control. Thus, it is necessary to continuously monitor the prevalence of IBDV. [Method] 36 IBDVs were identified from ten provinces in China from 2009 to 2012. Partial fragments of VP2, including the hypervariable region （HVR）, from new iso- lates were sequenced and analyzed through comparisons with published sequences of IBDV, including 18 strains isolated previously by our lab and 24 reference strains from China and around the world. [Result] Phylogenetic analysis showed a co-exis- tence of IBDV strains belonging to classic, variant, attenuated, and very virulent IB- DV （wlBDV） in China. wlBDVs remain the predominant strains in China and the new subgroup was emerging. Alignment analysis revealed several distinct amino acid mutations that might be involved in virulence or antigenicity variation. [Conclu- sion] The results offered evolutionary clues showing the emerging trend of obvious variations and diversity of IBDV in major poultry-producing regions of China particu- larly in recent years. These findings will contribute to a better understanding of the genetic evolution of IBDV.

Effects of Biological Pesticides on Prevention and Treatment of Virus Diseases in Greenhouse Tomato in Autumn

To alleviate the damage of tomato virus diseases, reduce chemical pesticide consumption and residue, and prevent environmental pollution, forecasting, randomized block design and statistical analysis were adopted to conduct field efficacy tests for Lentinan ＋ Gibberellin-heteroauxin-brassinolide （GHB） and Ningnanmycin ＋ GHB. The results showed that when the virus diseases in greenhouse tomato were serious, 0.5% Lentinan AS 3 000 ml ＋ GHB WP 600 g and 8% Ningnanmycin AS 900 ml ＋ GHB WP 600 g per hectare were applied 4 times with an interval of 7 days, and the control effects on the 10th, 17th, 26th and 35th day were above 88%, 87%, 78% and 67%, respectively. The difference in control effect of the two biological pesticides was insignificant, while their control effects were all significantly better than that of moroxydine hydrochloride （CK） ＋ GHB. The obtained results indicated that Lentinan ＋ GHB and Ningnanmycin ＋ GHB were the ideal biological pesticides, which could be used not only for controlling tomato virus diseases, but also for realizing modern, pollution-free, green and organic agricultural production.

Study on Screening of Virus Inhibitor Combinations against Viral Diseases in Chinese Cabbage

In this study, several kinds of virus inhibitors or passivators, such as Dufulin and lentinan, were used to design 15 individual or combination treatments, to investigate their control efficiency against viral diseases in Chinese cabbage. Re- sults showed that individual treatments of Dufulin and lentinan achieved high control efficiency of 70.01% and 66.02%, respectively; combination treatments of Dufulin ＋ lentinan, Dufulin ＋ Weijiaxi and Lentinan ＋Weijiaxi also produced certain synergistic effects, with control efficiency of 83.70%, 78.07% and 82.32%, respectively.

Vitamin D deficiency and hepatitis viruses-associated liver diseases:a literature review

The secosteroid hormone vitamin D has, in addition to its effects in bone metabolism also functions in the modulation of immune responses against infectious agents and in inhibiting tumorigenesis. Thus, deficiency of vitamin D is associated with several malignancies, but also with a plethora of infectious diseases. Among other communicable diseases, vitamin D deficiency is involved in the pathogenesis of chronic liver diseases caused by hepatitis B and C viruses(HBV, HCV) and high prevalence of vitamin D deficiency with serum levels below 20 mg/mL in patients with HBV and HCV infection are found worldwide. Several studies have assessed the effects of vitamin D supplementation on the sustained virological response(SVR) to interferon(IFN) plus ribavirin(RBV) therapy in HBV and HCV infection. In these studies, inconsistent results were reported. This review addresses general aspects of vitamin D deficiency and, in particular, the significance of vitamin D hypovitaminosis in the outcome of HBVand HCV-related chronic liver diseases. Furthermore,current literature was reviewed in order to understand the effects of vitamin D supplementation in combination with IFN-based therapy on the virological response in HBV and HCV infected patients.

Transfusion transmitted virus infection in general populations and patients with various liver diseases in south China

INTRODUCTIONAlthough several specific detecting methods hadbeen applied to determine the hepatitis virus,therewas a lot of cryptogenic hepatitis without anyknown hepatitis infectious marker.Theprevalence of hepatitis G virus (HGV) (also knownas GB-C virus) infection has been reported to be 5%-13% in patients with non-A-E hepatitis andcirrhosis,however,there is little evidencesuggesting that HGV causes hepatitis in human.

Epstein-Barr virus:Silent companion or causative agent of chronic liver disease?

The Epstein-Barr virus(EBV)has an important and multifaceted role in liver pathology.As a member of the herpes virus family,EBV establishes a persistent infection in more than 90%of adults.Besides acute hepatitis during primary infection,many clinical syndromes of interest for the hepatologist are associated with EBV infection.The role of EBV in the evolution of chronic hepatitis from hepatotropic viruses is considered.Chronic EBVassociated hepatitis is suspected in immunocompetent adults with compatible serology,suggestive histology and detection of the viral genome in the liver and/or increase of specific circulating cytotoxic T-lymphocytes.EBV is the main cause of post-transplant lymphoproliferative disorders which occur in up to 30%of cases.EBV-driven lymphoproliferative diseases are also recognized in non-immunocompromised patients and liver is involved in up to a third of the cases.Directly implicated in the pathogenesis of different tumors,EBV has a disputable role in hepatocellular carcinoma carcinogenesis.Further research is required in order to establish or reject the role of EBV in human liver cancer.This paper attempts to discuss the range of EBV-associated chronic liver diseases in immunocompetent patients,from mild,self-limiting mononuclear hepatitis to liver cancer.

Reactivation of hepatitis B virus infection in patients with hemolymphoproliferative diseases, and its prevention

Reactivation of hepatitis B virus(HBV)replication is characterized by increased HBV-DNA serum values of about 1 log or by HBV DNA turning positive if previously undetectable in serum,possibly associated with liver damage and seldom life-threatening.Due to HBV reactivation,hepatitis B surface antigen(HBsAg)-negative/anti-HBc-positive subjects may revert to HBsAg-positive.In patients with hemo-lymphoproliferative disease,the frequency of HBV reactivation depends on the type of lymphoproliferative disorder,the individual's HBV serological status and the potency and duration of immunosuppression.In particular,it occurs in 10%-50%of the HBsAg-positive and in 2%-25%of the HBsAg-negative/anti-HBc-positive,the highest incidences being registered in patients receiving rituximab-based therapy.HBV reactivation can be prevented by accurate screening of patients at risk and by a pharmacological prophylaxis with anti-HBV nucleo(t)sides starting 2-3 wk before the beginning of immunosuppressive treatment and covering the entire period of administration of immunosuppressive drugs and a long subsequent period,the duration of which depends substantially on the degree of immunodepression achieved.Patients with significant HBV replication before immunosuppressive therapy should receive anti-HBV nucleo(t)sides as a long-term(may be life-long)treatment.This review article is mainly directed to doctors engaged every day in the treatment of patients with onco-lymphoproliferative diseases,so that they can broaden their knowledge on HBV infection and on its reactivation induced by the drugs with high immunosuppressive potential that they use in the care of their patients.

Effect of Astragalus polysaccharides on Erythrocyte Immune Adherence of Chickens Inoculated with Infectious Bursal Disease Virus

Two hundred and forty specific pathogen free leghorn chickens were randomly divided into four groups and reared in isolated pens. The tested chickens were negative to infectious bursal disease virus （IBDV） at 25 d old. Group 1 was treated with saline, whereas Groups 2, 3, and 4 were inoculated with 0.3 mL IBDV suspension intranasally the next day. Groups 3 and 4 were also administered with Astragalus polysaccharides （APS） intramuscularly twice daily at 5 or 10 mg kg-1 BW, respectively, until 31 d old. The erythrocyte-C3b receptor rosette rate （E-C3bRR） and the erythrocyte-C3b immune complex rosette rate （E-ICRR） were measured at 25, 29, 32, 35, and 38 d old. The results showed that IBDV significantly reduced E-C3bRR and E-ICRR when compared with the control group （P 〈 0.05）, while simultaneous administration of APS with 1BDV maintained E-C3bRR at similar levels to the control group （P 〉 0.05） and increased E-ICRR when compared with the control group and the group non-treated with APS （P 〈 0.05）. APS treatment reduced the morbidity and mortality of chickens inoculated with IBDV （P 〈 0.05）. The results suggest that APS may enhance the immune adherence of chickens erythrocytes by affecting the activity and/or the number of complement receptors on the erythrocyte membrane. These findings can be beneficial in providing an understanding of the basic mechanisms required for the rational application of APS in modern medicine.

Modified model for end-stage liver disease improves shortterm prognosis of hepatitis B virus-related acute-on-chronic liver failure

AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum lactate.METHODS This clinical study was conducted at the First Affiliated Hospital, Fujian Medicine University, China. From 2009 to 2015, 236 patients diagnosed with HBV-related ACLF at our center were recruited for this 3-month followup study. Demographic data and serum lactate levels were collected from the patients. The MELD scores with or without serum lactate levels from survival and nonsurvival groups were recorded and compared.RESULTS Two hundred and thirty-six patients with HBV-ACLF were divided into two groups: survival group(S) andnon-survival group(NS). Compared with the NS group, the patients in survival the S group had a significantly lower level of serum lactate(3.11 ± 1.98 vs 4.67 ± 2.43, t = 5.43, P < 0.001) and MELD score(23.33 ± 5.42 vs 30.37 ± 6.58, t = 9.01, P = 0.023). Furthermore, serum lactate level was positively correlated with MELD score(r = 0.315, P < 0.001). Therefore, a modified MELD including serum lactate was developed by logistic regression analysis(0.314 × lactate + 0.172 × MELD-5.923). In predicting 3-month mortality using the MELD-LAC model, the patients from the S group had significantly lower baseline scores(-0.930 ± 1.34) when compared with those from the NS group(0.771 ± 1.32, t = 9.735, P < 0.001). The area under the receiver operating characteristic curve(AUROC) was 0.859 calculated by using the MELD-LAC model, which was significantly higher than that calculated by using the lactate level(0.790) or MELD alone(0.818). When the cutoff value was set at-0.4741, the sensitivity, specificity, positive predictive value and negative predictive value for predicting short-term mortality were 91.5%, 80.10%, 94.34% and 74.62%, respectively. When the MELD-LAC scores at baseline level were set at-0.5561 and 0.6879, the corresponding mortality rates within three months were 75% and 90%, respectively.CONCLUSION The short-term prognosis of HBV-related ACLF was improved by using a modified MELD including serum lactate from the present 6-year clinical study.

Application of Newcastle disease virus in the treatment of colorectal cancer

Colorectal cancer (CRC) is one of the main reasons of tumor-related deaths worldwide.At present,the main treatment is surgery,but the results are unsatisfactory,and the prognosis is poor.The majority of patients die due to liver or lung metastasis or recurrence.In recent years,great progress has been made in the field of tumor gene therapy,providing a new treatment for combating CRC.As oncolytic viruses selectively replicate almost exclusively in the cytoplasm of tumor cells and do not require integration into the host genome,they are safer,more effective and more attractive as oncolytic agents.Newcastle disease virus (NDV) is a natural RNA oncolytic virus.After NDV selectively infects tumor cells,the immune response induced by NDV’s envelope protein and intracellular factors can effectively kill the tumor without affecting normal cells.Reverse genetic techniques make NDV a vector for gene therapy.Arming the virus by inserting various exogenous genes or using NDV in combination with immunotherapy can also improve the anti-CRC capacity of NDV,and good results have been achieved in animal models and clinical treatment trials.This article reviews the molecular biological characteristics and oncolytic mechanism of NDV and discusses in vitro and in vivo experiments on NDV anti-CRC capacity and clinical treatment.In conclusion,NDV is an excellent candidate for cancer treatment,but more preclinical studies and clinical trials are needed to ensure its safety and efficacy.

Characteristics and advantages of adeno-associated virus vector-mediated gene therapy for neurodegenerative diseases

Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.

Vertically acquired hepatitis C virus infection:Correlates oftransmission and disease progression

The worldwide prevalence of hepatitis C virus(HCV)infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, motherto-child transmission(MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance(SVC) that usually occurs within 6 years of life. IL-28 B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.

Ebola virus disease: past, present and future

Ebola virus disease is one of the most deadly ailments known to mankind due to its high mortality rate(up to 90%) accompanying with the disease. Ebola haemorrhagic fever(EHF) is an infectious disease of animal that can be transmitted to both human and non-human primates. The first epidemic of EHF occurred in 1976 in the Democratic Republic of the Congo. The incubation period of ebola is less than 21 days. Ebola virus infections are depicted by immune suppression and a systemic inflammatory response that leads to damage of the vascular, coagulation and immune systems, causing multi-organ failure and shock. Five genetically distinct members of the Filoviridae family responsible for EHF are as follows: Zaire ebolavirus, Sudan ebolavirus, C?te d'Ivoire ebolavirus, Bundibugyo ebolavirus and Reston ebolavirus. The ongoing 2014 West Africa ebola epidemic has been considered as the most serious panic in the medical field with respect to both the number of human cases and death toll. The natural host for ebola virus is unknown, thus it is not possible to carry out programs to regulate or abolish virus from transmission to people. The ebola virus infection provides little chance to develop acquired immunity causing rapid progression of the disease. It is pertinent to mention that at present, there is no antiviral therapy or vaccine that is helpful against ebola virus infection in humans. The impediment of EHF necessitates much better understanding of the epidemiology of the disease, particularly the role of wildlife, as well as bats, in the spread of ebola virus to humans.

Epstein Barr virus-positive mucocutaneous ulcer of thecolon associated Hodgkin lymphoma in Crohn＇s disease

Epstein Barr virus （EBV） positive mucocutaneous ulcers（EBVMCU） form part of a spectrum of EBV-associatedlymphoproliferative disease. They have been reportedin the setting of immunosenescence and iatrogenicimmunosuppression, affecting the oropharyngeal mucosa,skin and gastrointestinal tract （GIT）. Case reports andseries to date suggest a benign natural history respondingto conservative management, particularly in the GIT. Wereport an unusual case of EBVMCU in the colon, arisingin the setting of immunosuppression in the treatment ofCrohn＇s disease, with progression to Hodgkin lymphoma18 mo after cessation of infliximab. The patient presentedwith multiple areas of segmental colonic ulceration,histologically showing a polymorphous infiltrate withEBV positive Reed-Sternberg-like cells. A diagnosisof EBVMCU was made. The ulcers failed to regressupon cessation of infliximab and methotrexate for 18mo. Following commencement of prednisolone for herCrohn＇s disease, the patient developed widespreadHodgkin lymphoma which ultimately presented as alife-threatening lower GIT bleed requiring emergencycolectomy. This is the first report of progression ofEBVMCU to Hodgkin lymphoma, in the setting of ongoingiatrogenic immunosuppression and inflammatory boweldisease.