The persistent infection of hepatitis B virus (HBV) is the result of lacking specific immunity against the virus. This state is also called immune tolerance to HBV. In most cases, acute HBV infection in adults can induce specific immune response which can clear the virus. Perinatal HBV infection, however, usually progresses to chronic infection, indicating a defect in HBV-specific immune response. A typical specific immune response includes four processes, which were antigen presentation, specific CD4 + T cell activation, specific CD8 + T cell activation and B cell activation. There must be some dysfunctions in some or all of the four processes during chronic HBV infection. This article discussed the relationship between chronic HBV infection and cellular immunity, hoping to provide a reference for further study on the reconstitution of specific immunity against HBV.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is the template for HBV transcription and replication and exists stably in hepatocytes in the form of minichromosome. Based on the mechanism of cccDNA inactivation or clearance and the development of related drugs, this article introduces the current knowledge on the formation, transcription, and degradation of cccDNA and reviews the research advances in cccDNA-targeted drugs and biological techniques.

The construction of "Double First-class" has started a new journey of higher education in China. Scientific, reasonable and objective evaluation on universities is the foundation and important guarantee for the construction of first-class universities. On the basis of introducing the main university evaluation system at home and abroad, the selection of representative Chinese and world university evaluation system for comparative study has strong guiding significance for the establishment of first-class university evaluation system. Under the background of "Double First-Class" construction, based on Chinese characteristics, the author puts forward some thoughts and suggestions on perfecting the university evaluation system in China.

Direct-acting antivirals (DAAs) play a critical role for the therapy of chronical hepatitis B. DAAs can decrease the production of viral progeny of hepatitis B virus (HBV), breaking the viral dynamic equilibrium between: (1) virion production from hepatocytes and clearance from circulation; (2) replenishment and decay of covalently closed circular (ccc)DNA pool inside infected hepatocytes. Nucleos(t)ide analogues can potently shift the first balance to undetectable viremia in the blood, but have limited or no effect on the second one, thus making it imperative to develop new agents targeting additional step(s) of HBV life cycle. We herein briefly introduce the DAAs currently in development by classifying them as agents affecting the replenishment or the decay of cccDNA pool.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is stably maintained in hepatocytes in the form of minichromosome and is considered the most important cause of chronicity of HBV infection, presence of HBV after antiviral therapy, and recurrence of hepatitis after drug withdrawal. However, due to a lack of antiviral regimens targeting cccDNA itself or the formation and transcription of cccDNA, there is an urgent need for treatment strategies targeting cccDNA. With the gradual understanding of epigenetic modification of histones of the cccDNA minichromosome, epigenetic therapy is expected to become a potential therapy for HBV. This article reviews the current status and future directions of HBV DNA methylation and cccDNA-bound histone modification, in order to provide new thoughts for epigenetic therapy for HBV.

Objective To investigate the seroepidemiology of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in adult men who have sex with men (MSM) in Chongqing area. Methods Nonprobability sampling method was used to test EB-CA-IgG, EB-NA-IgG and EB-VCA-IgM in the sera of 1082 MSMs from the clinical trials of HIV/AIDS treatments in Chongqing area from 2012 to 2015, and 1059 healthy individuals by means of enzyme-linked immunosorbent assay. The results were analyzed by Chi-square test. The difference was considered statistically significant when P<0.05. Results The 1082 MSM included 130 HIV positive and 952 HIV negative subjects. The prevalence of prior EBV infection was 92.6% in total MSM population, 88.5% in HIV-positive MSM, and 93.2% in HIV-negative MSM. The prevalence in total MSM and HIV negative MSM was significantly higher than that in control group (89.9%). Prior EBV infection was not?found?in?0.5%?of?the?total?MSM,?0.8%?of?HIV?positive?MSM?and?0.4%?of?HIV?negative?MSM,?all?significantly?lower?than?that?of control group (5.0%) (P<0.05).?Finally,?the?rate?of?EBV?reactivation?in?HIV?positive?MSM?(10.0%)?was?significantly?higher?than?that in control group (3.8%) and in HIV negative MSM group(4.1%) (P<0.005). Conclusions EBV infection is highly prevalent in MSM, higher than that in the general population. The rate of EBV reactivation in HIV negative MSM is similar to that in general population. The rate of seroepidemiology-based EBV reactivation is significantly higher in HIV positive MSM, which may be associated with the immunocompromised status post HIV infection.

Objective Knowledge-motivation-psychological model was set up and tested through structural equation model to provide evidence on HIV prevention related strategy in Men who have Sex with Men (MSM).Methods Snowball sampling method was used to recruit a total of 550 MSM volunteers from two MSM Non-Governmental Organizations in Urumqi,Xinjiang province.HIV prevention related information on MSM was collected through a questionnaire survey.A total of 477 volunteers showed with complete information.HIV prevention related Knowledge-motivationpsychological model was built under related experience and literature.Relations between knowledge,motivation and psychological was studied,using a ‘structural equation model’ with data from the fitting questionnaires and modification of the model.Results Structural equation model presented good fitting results.After revising the fitting index:RMSEA was 0.035,NFI was 0.965 and RFI was 0.920.Thereafter the exogenous latent variables would include knowledge,motivation and psychological effects.The endogenous latent variable appeared as prevention related behaviors.The standardized total effects of motivation,knowledge,psychological on prevention behavior were 0.44,0.41 and 0.17 respectively.Correlation coefficient of motivation and psychological effects was 0.16.Correlation coefficient on knowledge and psychological effects was-0.17 (P＜0.05).Correlation coefficient of knowledge and motivation did not show statistical significance.Conclusion Knowledge of HIV and motivation of HIV prevention did not show any accordance in MSM population.It was necessary to increase the awareness and to improve the motivation of HIV prevention in MSM population.

Objective To optimize the method of transcription activator‐like effector transcription factors (TALE‐TFs) con‐struction ,some improvement and adaption were made based on the traditional methods .Methods We first constructed the basic tandem fragments with different length ,including trimer ,tetramer ,pentamer and hexamer by Golden Gate cloning technique and PCR ,then the procedure with the highest efficacy was chosen to construct our TALE‐TFs .To determine the function of the TALE‐TFs ,the plasmid pminCMV with the specific binding sequence of TALE‐TFs was constructed by fragment substitution reaction (FSR) .The transcription activating function of TALE‐TFs was confirmed by the intensity of red fluorescence ,after TALE‐TFs , pEGFP‐N1 and pminCMV plasmid were co‐transfected into 293HEK cells .Results An optimized method for TALE‐TFs construc‐tion and functional assay was established .Conclusion This method can potentially be wildly used in fields that the expression of some constitutively expressed genes needs to be modified .

OBJECTIVETo generate a mouse model of chronic hepatitis B (CHB) infection by performing in vivo transduction of hepatitis B virus (HBV) covalently closed circular (ccc)DNA.

METHODSNude mice were injected with HBV cccDNA at doses of 1.5, 1.0 or 0.5 mug/ml. A control group was generated by giving equal injection volumes of physiological saline. The serum levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) on post-injection days 1 and 3, weeks 1-6, 8 and 10 were assayed by reflection immunoassay. At post-injection week 10, all animals were sacrificed and liver tissues were collected. Copies of HBV DNA in serum and liver tissue were detected by real-time PCR. HBV antigens in liver tissue were detected of by immunohistochemistry. Pathological analysis of liver tissue carried out with hematoxylin-eosin staining. Linear correlation of data was determined by statistical analysis.

RESULTSHBsAg and HBeAg were detected in sera from all three groups of cccDNA-injected mice staring at post-injection day 1 and lasting through week 10. The levels of HBsAg over the 10-week period showed two patterns of increase-decrease;the lowest level was detected at week 4 and the highest level was detected at week 8. In contrast, the levels of HBeAg over the 10-week period showed three patterns of increase-decrease; the lower levels were detected at weeks 2 and 4 and the higher levels at weeks 3 and 6. HBV DNA copies in liver tissues showed a cccDNA dose-dependent descending trend over the 10-week study period (1.5 mug/ml:1.14E+07 ± 6.51E+06 copies/g, 1.0 mug/ml:9.81E+06 ± 9.32E+06 copies/g, and 0.5 mug/ml:3.72E+06 ± 2.35E+06 copies/g; Pearson's r =0.979). HBV DNA copies in sera showed the pattern of 1.0 mug/ml cccDNA more than 1.5 mug/ml cccDNA more than 0.5 mug/ml cccDNA, and in general were higher than those detected in the liver tissues. Liver tissues from all cccDNA-injected mice showed positive immunohistochemistry staining for both HBsAg and HBeAg. HE staining showed that the liver tissues of all cccDNA-injected mice had severe fatty and vacuolar degeneration and less obvious structure of liver lobules (compared to the liver tissues from control mice).

CONCLUSIONThe CHB mouse model successfully established in this study by in vivo transduction of HBV cccDNA may represent a useful tool to study the pathogenic mechanisms and potential antiviral treatments of human CHB.

Animals ; DNA, Circular ; administration & dosage ; DNA, Viral ; administration & dosage ; Disease Models, Animal ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; physiology ; Hepatitis B, Chronic ; virology ; Male ; Mice ; Mice, Nude ; Transduction, Genetic ; Virus Replication