Shengli Bi

Neuraminidase and hemagglutinin matching patterns of a highly pathogenic avian and two pandemic H1N1 influenza A viruses.

Background Influenza A virus displays strong reassortment characteristics, which enable it to achieve adaptation in human infection. Surveying the reassortment and virulence of novel viruses is important in the prevention and control of an influenza pandemic. Meanwhile, studying the mechanism of reassortment may accelerate the development of anti-influenza strategies. Methodology/Principal Findings The hemagglutinin (HA) and neuraminidase (NA) matching patterns of two pandemic H1N1 viruses (the 1918 and current 2009 strains) and a highly pathogenic avian influenza A virus (H5N1) were studied using a pseudotyped particle (pp) system. Our data showed that four of the six chimeric HA/NA combinations could produce infectious pps, and that some of the chimeric pps had greater infectivity than did their ancestors, raising the possibility of reassortment among these viruses. The NA of H5N1 (A/Anhui/1/2005) could hardly reassort with the HAs of the two H1N1 viruses. Many biological characteristics of HA and NA, including infectivity, hemagglutinating ability, and NA activity, are dependent on their matching pattern. Conclusions/Significance Our data suggest the existence of an interaction between HA and NA, and the HA NA matching pattern is critical for valid viral reassortment.

Hepatitis A outbreaks in China during 2006: application of molecular epidemiology

BackgroundIn China, hepatitis is a huge public health problem. Outbreaks of hepatitis A are the most frequent cause of acute hepatitis, and to date, few epidemiologic investigations or molecular surveillance studies have been performed.Materials and methodsIn 2006, two major outbreaks of hepatitis A occurred, one in Guigang City, southern China, and the other in Hetian City, northwestern China. Field and molecular epidemiologic investigations were conducted.ResultsIn Guigang, a single outbreak occurred in a school; 35 patients and 25 asymptomatic individuals were infected with 1 strain of hepatitis A virus (HAV). A case-control study showed that contaminated water was the likely transmission source. In Hetian, the epidemic of hepatitis A consisted of sporadic, small outbreaks involving as many as 20 wild HAV strains. A molecular epidemiology approach allowed us to identify two groups infected by individual HAV strains. Further fieldwork and a case-control study showed that ice cream was the suspected transmission source in one group. Our molecular epidemiology study showed that genetic variability between the HAV strains isolated from Guigang and Hetian and previously reported HAV strains was at least 4.3%.ConclusionContaminated water and suspected ice cream were associated with outbreaks of hepatitis A. Viral genetic analysis may advance field investigations in complex situations.

Epidemiology of hepatitis E virus in China: results from the Third National Viral Hepatitis Prevalence Survey, 2005-2006.

In China, hepatitis E virus (HEV) is prevalent and causes disease, but its epidemiological profile is not well understood. We used a commercial enzyme-linked immunosorbent assay to detect total antibodies to hepatitis E virus in 15,862 serum samples collected during the Third National Viral Hepatitis Prevalence Survey. The results were analyzed to calculate estimates of HEV seroprevalence and to examine the effects of some putative risk factors. The seroprevalence of HEV in the general Chinese population during the period from 2005 through 2006 was 23.46% (95% confidence interval [CI], 18.41%–28.50%). The farming population, the age group of 15–60 year olds, and those living in the Midwest or Mideast region and in Xinjiang province had the highest seroprevalence estimates. The prevalence of HEV is high in China. The seroprevalence rate of HEV shows an unbalanced distribution among areas with different geographic location and economic development levels. The characteristics of the distribution associated may be due to the route of HEV transmission (via contaminated water or animal reservoirs). Within the same region, the seroprevalence of HEV is generally increased with age.

Hemagglutinin and neuraminidase matching patterns of two influenza A virus strains related to the 1918 and 2009 global pandemics

Abstract The current pandemic influenza A (H1N1) virus has revealed a complicated reassortment of various influenza A viruses. The biological study of these viruses, especially of the viral envelope proteins hemagglutinin (HA) and neuraminidase (NA), is urgently needed for the control and prevention of H1N1 viruses. We have generated H1N1-2009 and H1N1-1918 pseudotyped particles (pp) with high infectivity. Combinations of HA1918+NA2009 and HA2009+NA1918 also formed infectious H1N1pps, among which the HA2009+NA1918 combination resulted in the most highly infectious pp. Our study demonstrated that some reassortments of H1N1 viruses may hold the potential to produce higher infectivity than do their ancestors.

Efficacy of yeast-derived recombinant hepatitis B vaccine after being used for 12 years in highly endemic areas in China.

OBJECTIVE To evaluate the long-term efficacy and duration of yeast-derived recombinant hepatitis B vaccine in hepatitis B virus (HBV)-endemic areas. METHOD A cross-sectional investigation was carried out in five HBV-endemic areas. Children who were born between 1997 and 2008 and vaccinated with yeast-derived recombinant hepatitis B vaccine were selected. Serum samples were taken to test HBV infection markers by microparticle enzyme immunoassay, and the results were compared to those before vaccination. RESULTS 7066 subjects were enrolled. The average adjusted hepatitis B surface antigen (HBsAg) prevalence was 1.02%. HBV core antibody (anti-HBc) prevalence was 3.54%. The overall percentage of HBsAg(-)&Anti-HBc(-)&Anti-HBs(+) was 61.34%. With time after immunization, the percentage annually decreases from 86.11% in 2008 to 49.80% in 1997. Geometric mean concentration (GMC) of anti-HBs decreased significantly annually. The portion of GMC=100-999.9 mIU/ml was 48.0% in 2008, and decreased to 16.7% in 1997. CONCLUSION HBsAg prevalence decreased dramatically. This shows that the yeast-derived recombinant hepatitis B vaccine is effective and stable after being used for 12 years in HBV-endemic areas. It is not suggested to carry out booster immunization.

Enhanced mucosal immune responses induced by a combined candidate mucosal vaccine based on Hepatitis A virus and Hepatitis E virus structural proteins linked to tuftsin.

Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are the most common causes of infectious hepatitis. These viruses are spread largely by the fecal-oral route and lead to clinically important disease in developing countries. To evaluate the potential of targeting hepatitis A and E infection simultaneously, a combined mucosal candidate vaccine was developed with the partial open reading frame 2 (ORF2) sequence (aa 368–607) of HEV (HE-ORF2) and partial virus protein 1 (VP1) sequence (aa 1–198) of HAV (HA-VP1), which included the viral neutralization epitopes. Tuftsin is an immunostimulatory peptide which can enhance the immunogenicity of a protein by targeting it to macrophages and dendritic cells. Here, we developed a novel combined protein vaccine by conjugating tuftsin to HE-ORF2 and HA-VP1 and used synthetic CpG oligodeoxynucleotides (ODNs) as the adjuvant. Subsequent experiments in BALB/c mice demonstrated that tuftsin enhanced the serum-specific IgG and IgA antibodies against HEV and HAV at the intestinal, vaginal and pulmonary interface when delivered intranasally. Moreover, mice from the intranasally immunized tuftsin group (HE-ORF2-tuftsin + HA-VP1-tuftsin + CpG) showed higher levels of IFN-γ-secreting splenocytes (Th1 response) and ratio of CD4+/CD8+ T cells than those of the no-tuftsin group (HE-ORF2 + HA-VP1 + CpG). Thus, the tuftsin group generated stronger humoral and cellular immune responses compared with the no-tuftsin group. Moreover, enhanced responses to the combined protein vaccine were obtained by intranasal immunization compared with intramuscular injection. By integrating HE-ORF2, HA-VP1 and tuftsin in a vaccine, this study validated an important concept for further development of a combined mucosal vaccine against hepatitis A and E infection.

Molecular epidemiological study of hepatitis B virus genotypes in Southwest, China

Hepatitis B virus (HBV) is highly endemic in Southwest China; an area with many ethnic minorities. Information about the genetic distribution of HBV is still limited. In 2010, a multistage cluster sampling method was carried out in the Southwest China. Five hundred forty serum samples of participants were collected. Polymerase chain reaction followed by nucleotide sequencing of parts of the HBV S and C genes was performed. HBV genotype and subgenotype were determined. Recombination analysis was carried out. HBV infectious markers, HBV DNA and mutations in the basic core promoter (BCP) A1762T/G1764A and G1896A were analyzed. The results show us that HBV genotypes C/D recombinant (38.6%), B (31.6%), and C (23.3%), were predominant in Southwest China. C/D4 (96.8%) was endemic in the Tibetan and B2 (43.5%) in Han, and C1 (66.7%) was predominant in the Yi minority. 67.5% (56/83) of genotype C/D was Hepatitis B surface antigen (HBsAg) positive/Hepatitis B e antigen (HBeAg) positive/HBV DNA≥20,000 IU/ml, BCP A1762T/G1764A double mutation was frequent in genotype C and C/D, and G1896A was frequent in B and B/C. Thus, HBV genotypes distribution differed significantly in area and minority in Southwest China. C/D recombinant is endemic in the Tibetan, while B, C genotypes are predominant in Han minority. C/D recombinant exhibits higher frequency with HBeAg positive, high level of HBV DNA and BCP A1762T/G1764A double mutation. J. Med. Virol. 86:1307–1313, 2014.

The long-term efficacy, 13-23 years, of a plasma-derived hepatitis B vaccine in highly endemic areas in China.

OBJECTIVE To evaluate the long-term effectiveness of the plasma-derived hepatitis B vaccine that has been applied widely in five areas of China where HBV prevalence was highly endemic. METHOD A cross-sectional investigation was conducted in 2009 at five HBV surveillance sites around China. The target study subjects of 6772 were born between 1986 and 1996 and received plasma-derived HBV vaccine. Serum samples were collected to test for HBV markers using the microparticle enzyme immunoassay. RESULTS The number of participants enrolled was 6772. The average hepatitis B surface antigen (HBsAg) prevalence was 2.01%. The birth dose group included 5052 children. In this group, the average positive rates of HBsAg and hepatitis B core antibody (anti-HBc) were 1.58% and 6.39%, respectively, and these values declined gradually from 1986 to 1996. The positive rates of anti-hepatitis B surface antibody (HBs) and the geometric mean concentration (GMC) of anti-HBs-positive subjects were 41.69% and 115.8mIU/ml. CONCLUSION The long-term effectiveness of the plasma-derived hepatitis B vaccine still provided protection 13-23 years after vaccination. It seems that a booster dose is not necessary. Enhancing the rate of the birth dose within 24h is one of the most important measures to prevent and control HBV infection.

Development of a hepatitis delta virus antibody assay for study of the prevalence of HDV among individuals infected with hepatitis B virus in China

Co‐infection with hepatitis delta virus (HDV) and hepatitis B virus (HBV) has been shown to be associated with a more severe form of acute and chronic hepatitis. Cloning and expression of recombinant HDV antigen (rHDAg) in Escherichiacoli are described. Using purified rHDAg, a cost‐effective indirect anti‐HDV enzyme‐linked immunosorbent assay (ELISA) kit was developed. Direct comparison of 15 known HDV‐positive sera and 15 HDV‐negative sera showed concordance agreement between the new assay kit and the Abbott Murex Anti‐Delta (total) kit. In addition, 1,486 hepatitis B surface antigen (HBsAg) positive blood samples collected from various areas of China were tested using this indirect anti‐HDV ELISA. It was found that 1.2% (95% CI: 0.7–1.9%) of the samples were anti‐HDAg positive. It is suggested that the prevalence of HDV and HBV co‐infection in China is relatively low. J. Med. Virol. 84:445–449, 2012.

Prevalence and risk factors of hepatitis C among former blood donors in rural China

BACKGROUND Illegal commercial plasma and blood donation activities in the late 1980s and early 1990s caused a large number of hepatitis C virus (HCV) infections in rural areas of China. METHODS A cross-sectional survey was carried out in 2008, in which all residents in a former blood donation village in rural Hebei Province were invited for a questionnaire interview and testing for HCV antibodies. Questionnaires were administered to collect information about their personal status and commercial blood donation history, and HCV antibodies were tested by enzyme immunoassay. RESULTS Of 520 villagers who participated in the interviews, 236 (45.4%) reported a history of selling whole blood or plasma. HCV seropositivity was confirmed in 148/520 (28.5%) interviewees and 101/236 (42.8%) former commercial plasma and blood donors. Selling plasma was the strongest independent predictor of HCV seropositivity (p=0.0037). Past history of an operation was also independently associated with HCV infection (p=0.0270). CONCLUSIONS Unsafe practices during illegal plasma donation led to a high risk of HCV seropositivity for donors during the late 1980s and early 1990s. Many infected people suffered chronic hepatitis from that time onwards and urgently needed treatment and care.