Zhongjun Shao

Mother-to-infant transmission of hepatitis B virus: a Chinese experience.

Over 90% of infants infected with hepatitis B virus (HBV) caused by mother‐to‐infant transmission will evolve to carrier status, and this cannot be prevented until widespread administration of the HB vaccine and hepatitis B immune globulin (HBIG) is implemented. This prospective study of 214 infants born to HBsAg‐positive mothers was carried out to determine if either perinatal or intrauterine HBV transmission could be effectively prevented with HBIG and the HB vaccine. Peripheral blood was collected from mothers and from newborns before they received HBIG and the HB vaccine, as well as at 0, 1, 7, 24, and 36 months after birth. Infants born with an ratio of signal to noise(S/N) value of >5 for HBsAg (ABBOTT Diagnostic Kit) were defined as mother‐to‐infant transmission cases, those with an S/N between 5 and 50 were classified as perinatal transmission cases, and those with an S/N >50 were considered intrauterine transmission cases. Mother‐to‐infant transmission occurred in approximately 4.7% (10/214) of the infants; the perinatal transmission and intrauterine transmission rates were 3.7% (8/214) and 0.9% (2/214), respectively. The risk of mother‐to‐infant transmission increased along with maternal HBeAg or HBVDNA levels. After 36 months of follow‐up, all perinatal cases became HBsAg‐negative, whereas all intrauterine transmission cases evolved into carrier status. These results indicate that infants infected via intrauterine transmission cannot be effectively protected by HBIG and HB vaccine. J. Med. Virol. 83:791–795, 2011.

Analysis of recombination and natural selection in human enterovirus 71

The development of effective vaccines and antiviral prophylaxis against human enterovirus 71 (EV71) has been hampered by the extensive antigenic diversity of the virus. To gain new insights into the evolutionary processes that create this genetic diversity, the TreeOrder Scan Method and RDP program were employed to detect recombination events in the genome, and then parsimony-based and maximum-likelihood-based methods were used to detect natural selection effects on viral proteins. Recombination analysis provided strong evidence for recombination events in the majority of the sequences analyzed. Recombination events were found to be distributed nonrandomly with the highest frequency at the 3D region. Furthermore, positive selection was only detected at site 145 of VP1 by the maximum likelihood-based method. These results reveal that EV71 proteins are extensively influenced by stabilizing selection. We conclude that recombination may play a more important role than positive selection in the formation of genetic diversity.

A Population-Based Study Examining Hepatitis B Virus Infection and Immunization Rates in Northwest China

Background and Aim Current baseline data regarding the prevalence of hepatitis B virus (HBV) infections and the immune status in hyperendemic areas is necessary in evaluating the effectiveness of ongoing HBV prevention and control programs in northwest China. This study aims to determine the prevalence of chronic HBV infections, past exposure rates, and immune response profiles in Wuwei City, northwest China in 2010. Methods Cross-sectional household survey representative of the Wuwei City population. 28,579 participants were interviewed in the seroepidemiological survey ≥1 year of age. House to house screening was conducted using a standard questionnaire. All serum samples were screened by enzyme-linked immunoassays for the presence of hepatitis B surface antigen, antibodies against HBV surface antigen, and antibodies to the hepatitis B core antigen. Results Among individuals ≥1 year of age, 7.2% (95%CI: 6.3–8.1%) had chronic HBV infections, 43.9% (CI: 40.4–47.4%) had been exposed to HBV, and 23.49% (CI: 21.6–25.3%) had vaccine-induced immunity. Multi-factor weighted logistic regression analysis showed that having household contact with HBV carriers (OR = 2.6, 95%CI: 2.3–3.0) and beauty treatments in public places (OR = 1.2, 95%CI: 1.1–1.3) were the risk factors of HBV infection in whole population. Having household contact with HBV carriers (OR = 3.8, 95% CI: 2.2–6.5) and lack of hepatitis vaccination (OR = 2.0, 95% CI: 1.4–3.3) were the risk factors for HBV infection in children aged 1–14 years. Conclusions Hepatitis B infection remains a serious public health problem in northwest China. Having household contact with HBV carriers and beauty treatments in public places represented HBV infection risk factors. Hepatitis B vaccine immunization strategies need further improvement, particularly by targeting the immunization of rural migrant workers.

Establishment and characterization of a spontaneously immortalized trophoblast cell line (HPT-8) and its hepatitis B virus-expressing clone

BACKGROUND Most trophoblast cell lines currently available to study vertical transmission of hepatitis B virus (HBV) are immortalized by viral transformation. Our goal was to establish and characterize a spontaneously immortalized human first-trimester trophoblast cell line and its HBV-expressing clone. METHODS Chorionic villi of Asian human first-trimester placentae were digested with trypsin and collagenase I to obtain the primary trophoblast cell culture. A spontaneously immortalized trophoblast cell line (HPT-8) was analyzed by scanning and transmission electron microscopy, cell cycle analysis, immunohistochemistry and immunofluorescence. HPT-8 cells were stably transfected with the adr subtype of HBV (HPT-8-HBV) and characterized by PCR and enzyme-linked immunosorbent assay. RESULTS We obtained a clonal derivative of a spontaneously immortalized primary cell clone (HPT-8). HPT-8 cells were epithelioid and polygonal, and formed multinucleate, giant cells. They exhibited microvilli, distinct desmosomes between adjacent cells, abundant endoplasm, lipid inclusions and glycogen granules, which are all characteristic of cytotrophoblasts. HPT-8 cells expressed cytokeratin 7, cytokeratin 18, vimentin, cluster of differentiation antigen 9, epidermal growth factor receptor, stromal cell-derived factor 1 and placental alkaline phosphatase. They secreted prolactin, estradiol, progesterone and hCG, and were positive for HLA-G, a marker of extravillous trophoblasts. HPT-8-HBV cells were positive for HBV relaxed-circular, covalently closed circular DNA and pre-S sequence. HPT-8-HBV cells also produced and secreted HBV surface antigen and HBV e antigen. CONCLUSIONS We established a trophoblast cell line, HPT-8 and its HBV-expressing clone which could be valuable in exploring the mechanism of HBV viral integration in human trophoblasts during intrauterine infection.

Recombination and Natural Selection in Hepatitis E Virus Genotypes

To gain new insights into the evolutionary processes that created the genetic diversity of the hepatitis E virus (HEV), the Recombination Detection Program (RDP) and SimPlot program were employed to detect recombination events in the genome, then the fixed‐effects likelihood (FEL) method was used to detect natural selection effects on viral proteins. Recombination analysis provided strong evidence for both intergenotype and intragenotype recombination events in the sequences analyzed. Recombination events were found to be distributed non‐randomly, with the highest frequency in the X domain and the helicase. Strain DQ450072 was identified as intergenotype‐recombinant. Natural selection analysis revealed that codons under both negative selection and positive selection were distributed non‐randomly. ORF1 and ORF2 have experienced strong purifying selection across genotypes. Furthermore, potentially important sites were also found under positive selection in the N‐terminal end of ORF2 and the C‐terminal end of ORF3. No significant difference was found among the selective pressures on different genotypes. J. Med. Virol. 84:1396–1407, 2012.

Epidemiology of Hepatitis B Virus Infection in China: Current Status and Challenges

The prevalence of hepatitis B is high in China. Based on the National Disease Supervision Information Management System of China, the mean reported incidence of hepatitis B was 84.3 per 100,000 in China between 2005 and 2010. There are differences in population distribution based on region and ethnic group. Here, risk factors, virological characteristics, and prophylaxis of hepatitis B in China are reviewed. Although the prevalence of HBV infection is gradually declining, there are many challenges in HBV infection control, including higher prevalence in floating population, poor compliance of antiviral therapy, and high disease burden.

The Anti-Arthritic Effects of Synthetic Melittin on the Complete Freund's Adjuvant-Induced Rheumatoid Arthritis Model in Rats

Bee venom (BV) has been used for millennia in Chinese traditional medicine to treat rheumatoid arthritis (RA). However, its components and mechanism remain unclear, which has hampered its development and application for the treatment of RA. In this study, we examined the anti-arthritis effects of melittin, which composes nearly 50% of the dry weight of whole BV, on the complete Freunds adjuvant-induced (CFA-induced) RA model in rats. The RA animal models were treated with solutions of BV, melittin, and saline by injection into a specific acupoint (Zusanli). The BV and melittin treatments statistically diminished the thickness of the arthroses in the injected side of the paw, compared to the saline treatment. Melittin therapy also significantly reduced arthritis-induced nociceptive behaviors, as assessed by the thermal hyperalgesia test. In addition, CFA-induced Fos expression in the superficial layer of the lumbar spinal cord was significantly suppressed by the BV and melittin treatments, compared to the saline treatment. These results indicate that melittin is an effective anti-arthritis component of whole bee venom, making it a promising candidate as an anti-arthritis drug.

A description of the hepatitis B virus genomic background in a high-prevalence area in China

BackgroundHepatitis B (HB) is an important disease worldwide. Almost 350 million people are positive for Hepatitis B virus surface antigen (HBsAg), and one-third of them live in China. According to a nation-wide serosurvey in China in 2006, the prevalence of HBsAg was higher in Northwest China than in other areas. However, the epidemic HBV strains in this area are poorly studied.ResultsIn this study, 242 complete hepatitis B virus (HBV) genome sequences were obtained from HBV asymptomatic carriers in major cities of Northwest China. The 242 HBV sequences clustered into genotypes B, C and D. Through comparison of the genotype consensus sequences, 158 genotype-dependent positions were observed in P, S and X ORFs. Clinically relevant mutation screening in this study revealed that no HBV antiviral drug resistance mutations were observed and the vaccination failure mutations were heavily underrepresented.ConclusionsThe role of genotype D strains in HBV prevalence should not be ignored in Northwest China. Due to low prevalence of vaccination failure mutations, it can be inferred that the genotype B, C and D strains in Northwest China may have less likelihood of vaccine escape.

High-throughput simultaneous genotyping of human platelet antigen-1 to -16 by using suspension array

Comprehensive and accurate detection of human platelet antigens (HPAs) plays a significant role in diagnosis and prevention of the platelet (PLT) alloimmune syndromes and ensuring clinical safety of patients undergoing PLT transfusion. The majority of the available methods are incapable of performing high‐throughput simultaneous detection of HPA‐1 to ‐16, and the accuracy of many methods needs to be further enhanced.

Maternal immunization promotes the immune response of neonates towards hepatitis B vaccine.

Infants infected with hepatitis B virus (HBV) face the risk of developing severe complications. Unfortunately, in spite of universal vaccination programmes, 5% or more of vaccinated newborns still do not achieve protective levels of anti‐hepatitis B virus surface antigen titres (anti‐HBs). The aim of this study was to use animal experiments and population‐based research to determine whether maternal vaccination against HBV affects the outcome of neonatal vaccination. Six sows and 53 newborn piglets were used for this study and randomly assigned to the vaccination group (three 20 μg doses of recombinant HBV vaccine). All the piglets were followed up to 10 weeks of age, and peripheral blood was withdrawn for measurement of anti‐HBs. A cross‐sectional study was also conducted on 449 mothers with infants. A structured questionnaire was used to collect demographic, medical and maternal data, and their peripheral blood was collected for measurement of anti‐HBs. The results of animal experiments demonstrated that nonvaccinated piglets born to vaccinated sows and nonvaccinated piglets born to nonvaccinated sows were negative for anti‐HBs. Repeated measures analysis of variance showed that the titres of anti‐HBs in vaccinated piglets born to vaccinated sows were significantly higher than in vaccinated piglets born to nonvaccinated sows (P < 0.05). In a population‐based study, a cumulative logistic regression analysis showed that the strongest influences on neonatal anti‐HBs titres were delay of the first vaccination dose [OR = 3.02(95% CI: 1.72–5.30)] and maternal anti‐HBs titres [OR = 2.48(95% CI: 2.03–3.04)]. In conclusion, high maternal anti‐HBs titres can enhance the response to HBV vaccination in infants.