Japanese encephalitis is an acute zoonotic, mosquito-borne disease caused by Japanese encephalitis virus (JEV). Japanese encephalitis is characterized by extensive inflammation in the central nervous system (CNS) and disruption of the blood-brain barrier (BBB). However, the pathogenic mechanisms contributing to the BBB disruption are not known. Here, using a mouse model of intravenous JEV infection, we show that virus titers increased exponentially in the brain from 2 to 5 days postinfection. This was accompanied by an early, dramatic increase in the level of inflammatory cytokines and chemokines in the brain. Enhancement of BBB permeability, however, was not observed until day 4, suggesting that viral entry and the onset of inflammation in the CNS occurred prior to BBB damage. In vitro studies revealed that direct infection with JEV could not induce changes in the permeability of brain microvascular endothelial cell monolayers. However, brain extracts derived from symptomatic JEV-infected mice, but not from mock-infected mice, induced significant permeability of the endothelial monolayer. Consistent with a role for inflammatory mediators in BBB disruption, the administration of gamma interferon-neutralizing antibody ameliorated the enhancement of BBB permeability in JEV-infected mice. Taken together, our data suggest that JEV enters the CNS, propagates in neurons, and induces the production of inflammatory cytokines and chemokines, which result in the disruption of the BBB. IMPORTANCEJapanese encephalitis (JE) is the leading cause of viral encephalitis in Asia, resulting in 70,000 cases each year, in which approximately 20 to 30% of cases are fatal, and a high proportion of patients survive with serious neurological and psychiatric sequelae. Pathologically, JEV infection causes an acute encephalopathy accompanied by BBB dysfunction; however, the mechanism is not clear. Thus, understanding the mechanisms of BBB disruption in JEV infection is important. Our data demonstrate that JEV gains entry into the CNS prior to BBB disruption. Furthermore, it is not JEV infection per se, but the inflammatory cytokines/ chemokines induced by JEV infection that inhibit the expression of TJ proteins and ultimately result in the enhancement of BBB permeability. Neutralization of gamma interferon (IFN-␥) ameliorated the enhancement of BBB permeability in JEV-infected mice, suggesting that IFN-␥ could be a potential therapeutic target. This study would lead to identification of potential therapeutic avenues for the treatment of JEV infection. J apanese encephalitis (JE) is an acute zoonotic, mosquito-borne infectious disease caused by JE virus (JEV) infection. JEV is a single-stranded, positive-sense RNA virus, belonging to the genus Flavivirus of the family Flaviviridae (1, 2). JEV is a neurotropic virus and infection causes an acute encephalopathy. JE commonly affects children in the South Pacific regions of Asia (3, 4). Of nearly 70,000 cases of JE reported each year, ca. 20 to 30% of cases are fatal, and a high proport...

Etanercept effectively reduces the inflammation and provides protection against acute encephalitis in a JEV-infected mouse model.

BackgroundThe human papillomavirus (HPV) vaccines have been widely introduced in immunization programs worldwide, however, it is not accepted in mainland China. We aimed to investigate the awareness and knowledge about HPV vaccines and explore the acceptability of vaccination among the Chinese population.MethodsA meta-analysis was conducted across two English (PubMed, EMBASE) and three Chinese (China National Knowledge Infrastructure, Wan Fang Database and VIP Database for Chinese Technical Periodicals) electronic databases in order to identify HPV vaccination studies conducted in mainland China. We conducted and reported the analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsFifty-eight unique studies representing 19 provinces and municipalities in mainland China were assessed. The pooled awareness and knowledge rates about HPV vaccination were 15.95 % (95 % CI: 12.87–19.29, I2 = 98.9 %) and 17.55 % (95 % CI: 12.38–24.88, I2 = 99.8 %), respectively. The female population (17.39 %; 95 % CI: 13.06–22.20, I2 = 98.8 %) and mixed population (18.55 %; 95 % CI: 14.14–23.42, I2 = 98.8 %) exhibited higher HPV vaccine awareness than the male population (1.82 %; 95 % CI: 0.50–11.20, I2 = 98.5 %). Populations of mixed ethnicity had lower HPV vaccine awareness (9.61 %; 95 % CI: 5.95–14.03, I2 = 99.0 %) than the Han population (20.17 %; 95 % CI: 16.42–24.20, I2 = 98.3 %). Among different regions, the HPV vaccine awareness was higher in EDA (17.57 %; 95 % CI: 13.36–22.21, I2 = 98.0 %) and CLDA (17.78 %; 95 % CI: 12.18–24.19, I2 = 97.6 %) than in WUDA (1.80 %; 95 % CI: 0.02–6.33, I2 = 98.9 %). Furthermore, 67.25 % (95 % CI: 58.75–75.21, I2 = 99.8 %) of participants were willing to be vaccinated, while this number was lower for their daughters (60.32 %; 95 % CI: 51.25–69.04, I2 = 99.2 %). The general adult population (64.72 %; 95 % CI: 55.57–73.36, I2 = 99.2 %) was more willing to vaccinate their daughters than the parent population (33.78 %; 95 % CI: 26.26–41.74, I2 = 88.3 %). Safety (50.46 %; 95 % CI: 40.00–60.89, I2 = 96.6 %) was the main concern about vaccination among the adult population whereas the safety and efficacy (68.19 %; 95 % CI: 53.13–81.52, I2 = 98.6 %) were the main concerns for unwillingness to vaccinate their daughters.ConclusionsLow HPV vaccine awareness and knowledge was observed among the Chinese population. HPV vaccine awareness differed across sexes, ethnicities, and regions. Given the limited quality and number of studies included, further research with improved study designis necessary.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-016-2873-8) contains supplementary material, which is available to authorized users.

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