Zika virus (ZIKV), a re-emerging flavivirus associated with neurological disorders, has spread rapidly to more than 70 countries and territories. However, no specific vaccines or antiviral drugs are currently available to prevent or treat ZIKV infection. Here we report that a synthetic peptide derived from the stem region of ZIKV envelope protein, designated Z2, potently inhibits infection of ZIKV and other flaviviruses in vitro. We show that Z2 interacts with ZIKV surface protein and disrupts the integrity of the viral membrane. Z2 can penetrate the placental barrier to enter fetal tissues and is safe for use in pregnant mice. Intraperitoneal administration of Z2 inhibits vertical transmission of ZIKV in pregnant C57BL/6 mice and protects type I or type I/II interferon receptor-deficient mice against lethal ZIKV challenge. Thus, Z2 has potential to be further developed as an antiviral treatment against ZIKV infection in high-risk populations, particularly pregnant women.
Both bisphenol A (BPA) and triclosan (TCS) are phenolic compounds widely used in a variety of household applications. These compounds could be released into the environment, enter the human body and cause a series of potential health hazards. Children are sensitive and susceptible to these contaminants. To investigate the potential oxidative DNA damage from exposure to BPA and TCS, ninety six urine samples of children (aged 3-6) and 57 dust samples were collected from a kindergarten in Guangzhou, China. The concentrations of urinary BPA, TCS and 8-hydroxy-2'-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage) in urine were determined using a liquid chromatography tandem mass spectrometer. The geometric mean concentrations of urinary BPA, TCS and 8-OHdG were 1.08 μg L, 1.34 μg L and 1.90 μg L, respectively. The results showed that both BPA and TCS exposures were associated with oxidative damage. Significant dose-effects existed between the urinary BPA, TCS levels and the 8-OHdG concentrations. Multiple linear regression analysis showed that one percent increase in BPA and in TCS could generate 0.15% and 0.081% increase in 8-OHdG in urine for children in Guangzhou. We also determined the concentrations of BPA in dust using high performance liquid chromatography. The mean concentration of BPA was 2.86 μg g in indoor dust and 3.23 μg g in outdoor dust. The dust contributes approximately 9.23% to the urinary BPA exposure for the children. In conclusion, BPA and TCS exposure correlates with oxidative DNA damage.
After three decades of intensive research efforts, an effective vaccine against HIV-1 remains to be developed. Several broadly neutralizing antibodies to HIV-1, such as 10E8, recognize the membrane proximal external region (MPER) of the HIV-1 gp41 protein. Thus, the MPER is considered to be a very important target for vaccine design. However, the MPER segment has very weak immunogenicity and tends to insert its epitope residues into the cell membrane, thereby avoiding antibody binding. To address this complication in vaccine development, we herein designed a peptide, designated 10E8-4P, containing four copies of the 10E8 epitope as an immunogen. As predicted by structural simulation, 10E8-4P exhibits a well-arranged tandem helical conformation, with the key residues in the 10E8 epitope oriented at different angles, thus suggesting that some of these key residues may be exposed outside of the lipid membrane. Compared with a peptide containing a single 10E8 epitope (10E8-1P), 10E8-4P not only exhibited better antigenicity but also elicited neutralizing antibody response against HIV-1 pseudoviruses, whereas 10E8-1P could not induce detectable neutralizing antibody response. Importantly, antibodies elicited by 10E8-4P also possessed a strong ability to activate an antibody-dependent cell-mediated cytotoxicity (ADCC) reporter gene, thus suggesting that they may have ADCC activity. Therefore, this strategy shows promise for further optimization and application in future HIV-1 vaccine design.
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