Toll-like receptor 4 plays an anti-HBV role in a murine model of acute hepatitis B virus expression

AIM： Toll-like receptor 4 （TLR4） has been shown to be important for bacterial infection, especially to lipopolysaccharide signaling. Its possible role in HBV infection is studied in the present study. MATERIALS AND METHODS： pHBV3.6 plasmid, containing full-length HBV genome was used in the murine model of acute HBV expression by hydrodynamics in vivo transfection. TLR4 normal or mutant mouse strain was compared to investigate the possible role of TLR4 in acute HBV expression. RESULTS： After pHBV3.6 injection, the infiltrating leukocytes expressed TLR4 were observed nearby the HBsAg-expressing hepatocytes. The HBV antigenemia as well as the replication and transcription were higher in TLR4-mutant C3H/HeJ mice than in normal C3H/ HeN mice. The HBV-specific immune responses were impaired in the liver or spleen of the C3H/HeJ mice. Their inducible nitric oxide synthase （iNOS） expression on the hepatic infiltrating cells was also impaired. When adoptively transferring splenocytes from C3H/HeN mice to C3H/HeJ mice, the HBV replication was inhibited to the level as that of C3H/HeN. CONCLUSION： These results suggest that TLR4 plays an anti-HBV role in vivo through the induction of iNOSexpression and HBV-specific immune responses after HBV expression.

Dengue Vaccines: Challenge and Confrontation

Dengue has been recognized as one of the most important vector-borne human diseases. The disease is induced by dengue virus infection resulting from the bite of an infected Aedes spp. mosquito after imbibing the tainted blood from animals or patients. Dynamic clinical spectrums ranging from asymptomatic, undifferentiated fever, typical dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) have been well documented. Initially, the disease was mainly restricted in tropical and subtropical zones. However, with factors such as ineffective vector control, frequency of human migration, unplanned urbanization, and changing climate temperature, the disease has been spotted at almost every territory of the earth. Dengue has been associated with human disease for more than two centuries. Although classic DF is viewed as a self-limited illness, subjects normally resolve within two weeks and recover without any noticeable complications or sequelae, some of these infected individuals may progress to life-threatening DHF/DSS, characterized with plasma leakage due to an increase in capillary permeability. The significantly increased public health threat and the burden of morbidity and mortality of dengue globally has caught the attention of public officials and prompted an action to find a way to contain and prevent the disease. The lack of specific dengue therapeutics has led to an emphasis on vaccine development, one of the best and effective strategies to reduce and prevent the illness. Making a dengue vaccine has been attempted more than six decades;although some of these products are in clinical trials, vaccine development for the prevention of dengue disease is still at its infancy. So far no dengue vaccine is available for the public. Dengue vaccine development may be hindered by the complexity of the clinical presentations, which implicates that multiple pathogenic mechanisms are involved in dengue disease. Some of these elements will be discussed in the current review. Opening up discussion on these pros and cons and engaging in more research to understand these features would not only improve the understanding of the pathogenesis of the dengue virus infection but also pave a new tactic to develop a safer and effective dengue vaccine.