ABSTRACT
It is known that hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) persists in the nucleus of infected hepatocytes in the form of minichromosome and is difficult to target and eliminate. Studies on the mechanisms and strategies for persistent silencing or elimination of HBV cccDNA are the focus achieving for “functional cure” of chronic hepatitis B. This article introduces the current knowledge on the basic biological features of cccDNA, regulatory mechanisms of transcription and metabolism, and related host factors, with a focus on the potential pathways and strategies for cccDNA silencing or elimination.
ABSTRACT
In situ hybridization (ISH) is a new technique which combines molecular biology, histochemistry, and cytology. It can quantify and locate specific nucleic acids at the cellular and chromosomal levels and is widely used in virological research. ISH is of great significance for the detection of hepatitis B virus (HBV) nucleic acids (RNA and replicative intermediate DNA) and covalently closed circular DNA. This article reviews the development of ISH and its application in HBV research.
ABSTRACT
At present, interferon (IFN) and nucleos(t)ide analogues (NAs) remain the most important methods for the treatment of chronic hepatitis B in clinical practice, but neither of them can effectively eliminate the virus and cure hepatitis B. As the template for HBV transcription and replication, HBV covalently closed circular DNA (cccDNA) persistently exists in the nucleus in the form of minichromosome and is considered the most important reason for chronic and refractory HBV infection. Since it is hard to completely eliminate cccDNA, functional cure of chronic hepatitis B through sustained silencing of cccDNA has become a major goal of clinical and basic research in recent years. This article reviews the influence of current treatment methods on cccDNA, the factors regulating the amount and activity of cccDNA, and the key obstacles to eradication of cccDNA pool, with perspectives of cccDNA research towards a functional cure of chronic hepatitis B.
ABSTRACT
Hepatitis B virus (HBV) infection causes pathological changes of the liver,including liver inflammation,hepatocyte necrosis,and even liver fibrosis,and promotes the progression from chronic hepatitis to liver cirrhosis and liver cancer,but related mechanisms remain unclear.The mechanism for the interaction between hepatocytes infected by HBV and uninfected hepatocytes/host immune system might be exosomes-mediated cell-cell communication in liver microenvironment.Many studies have demonstrated that viral infection can regulate the production of exosomes and affect their composition,and viral microRNAs,proteins,and even the entire virion can be incorporated into the exosomes,which can affect the immune recognition of viruses or regulate the function of adjacent cells.This article elaborates on the production and composition of exosomes and their roles in viral infection,as well as the research advances in the association between exosomes and HBV infection.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the epidemiology characteristics of norovirus among diarrheal outpatients in China.</p><p><b>METHODS</b>Diarrhea cases were monitored at emergency/outpatient departments at 173 hospitals in 27 provinces of China, with clinical and epidemiological data, and fecal specimens collected and sent to 58 network-laboratories to detect norovirus by RT-PCR method, and to analyze the positive rate of norovirus in various regions, population and time during 2009-2013.</p><p><b>RESULTS</b>11.6% of the 34 031 diarrheal cases under surveillance were found with norovirus. Age group of 6-23 month-old children and that of people over 45 years old were found with the highest positive percentage, 13.7% and 12.4% respectively. Positive percentage of norovirus peaks in autumn and winter in a year; it peaks in mid-temperate zones (10.7%) and warm-temperate zones (11.6%) in winter. It peaks in sub-tropical zones in autumn (14.3%). The most prevalent genogroups detected were norovirus G II, accounting for 89.9% of identified strains.</p><p><b>CONCLUSION</b>Norovirus affects all ages and was most prevalent in children and the elderly among diarrhea outpatients. Norovirus' positive percentage showed strong seasonal pattern, and peaks at different times of a year in different climate zones of China. Since no effective preventive measures existed, further study on norovirus epidemiology and intervention strategies should be conducted in future.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Humans , Middle Aged , Caliciviridae Infections , Epidemiology , China , Epidemiology , Diarrhea , Epidemiology , Virology , Genotype , Hospitals , Laboratories , Norovirus , Outpatients , Prevalence , SeasonsABSTRACT
<p><b>BACKGROUND</b>To elucidate relationship between amino acid sequence of non-structural protein 5A (NS5A) and outcome of HCV (1 b) patients after interferon (IFNa) therapy.</p><p><b>METHODS</b>Sera of 24 patients were collected before, during and after IFNa therapy. Pretreatment RNA levels and the sequences of HCV NS5A interferon sensitivity determining region (ISDR) were determined. NS5A full-length sequences of 5 HCV isolates from 3 patients with different response types were also analyzed. Phylogenetic tree analysis and protein secondary structure prediction were undertaken.</p><p><b>RESULTS</b>Pretreatment RNA levels of sustained response group were significantly lower than that of non-response group and relapse group (4.50X104 copies/ml versus 1.82X107 copies/ml, P < 0.01).ISDR sequences of NS5A from pretreatment sera were compared with HCV-J strain (prototype). Thirteen of 24 isolates were wild type,11 of 24 were intermediate type and none of them was mutant type. 3 of 6 sustained responders were infected with wild-type isolates, the rest with intermediate type isolates. Phylogenetic tree based on NS5A full-length sequences classified 5 isolates with 3 different response types into 3 groups. Non-response isolates belonged to the same group as HCV-J. Secondary structure prediction of 5 isolates revealed significant differences existing in 2 255- 2 289. This region was partly overlapped with PKR-binding domain.</p><p><b>CONCLUSIONS</b>Low HCV RNA levels in serum are associated with favorable outcome of IFNa therapy. ISDR sequence alone could not predict outcome of IFN treatment. Combination of determination of HCV RNA levels in serum with sequence analysis of PKR-binding domain may be helpful in predicting the efficacy of IFN therapy.</p>
Subject(s)
Humans , Amino Acid Sequence , Antiviral Agents , Therapeutic Uses , Hepacivirus , Genetics , Hepatitis C, Chronic , Drug Therapy , Virology , Interferon-alpha , Therapeutic Uses , RNA, Viral , Blood , Viral Nonstructural Proteins , GeneticsABSTRACT
Objective To evaluate the prevalence and clinic relevance of hepatitis G virus(HGV)infection in maintenance hemodialysis patients. Methods Reverse-transcription(RT) nested polymerase chain reaction(PCR)was used to detect HGV in 50 HD patients. The prevalence of HGV infection, their relationship with risk factors, liver function and HBV, HCV infection were investigated. Results HGV RNA was found in 14 percent of the HD patients (7 of 50), as compared with none of health blood donors(0 of 20, P