The development of vaccines against infectious diseases represents one of the most important contributions to medical science. However, vaccine-preventable diseases still cause millions of deaths each year due to the thermal instability and poor efficacy of vaccines. Using the human enterovirus type 71 vaccine strain as a model, we suggest a combined, rational design approach to improve the thermostability and immunogenicity of live vaccines by self-biomineralization. The biomimetic nucleating peptides are rationally integrated onto the capsid of enterovirus type 71 by reverse genetics so that calcium phosphate mineralization can be biologically induced onto vaccine surfaces under physiological conditions, generating a mineral exterior. This engineered self-biomineralized virus was characterized in detail for its unique structural, virological, and chemical properties. Analogous to many exteriors, the mineral coating confers some new properties on enclosed vaccines. The self-biomineralized vaccine can be stored at 26°C for more than 9 d and at 37°C for approximately 1 wk. Both in vitro and in vivo experiments demonstrate that this engineered vaccine can be used efficiently after heat treatment or ambient temperature storage, which reduces the dependence on a cold chain. Such a combination of genetic technology and biomineralization provides an economic solution for current vaccination programs, especially in developing countries that lack expensive refrigeration infrastructures.genetic engineering | vaccine design | shell

Systemic lupus erythematosus (SLE) is characterized by high-titer serological autoantibodies, including antibodies that bind to double-stranded DNA (dsDNA). The origin, specificity, and pathogenicity of anti-dsDNA antibodies have been studied from a wider perspective. These autoantibodies have been suggested to contribute to multiple end-organ injuries, especially to lupus nephritis, in patients with SLE. Moreover, serum levels of anti-DNA antibodies fluctuate with disease activity in patients with SLE. By directly binding to self-antigens or indirectly forming immune complexes, anti-dsDNA antibodies can accumulate in the glomerular and tubular basement membrane. These autoantibodies can also trigger the complement cascade, penetrate into living cells, modulate gene expression, and even induce profibrotic phenotypes of renal cells. In addition, the expression of suppressor of cytokine signaling 1 is reduced by anti-DNA antibodies simultaneously with upregulation of profibrotic genes. Anti-dsDNA antibodies may even participate in the pathogenesis of SLE by catalyzing hydrolysis of certain DNA molecules or peptides in cells. Recently, anti-dsDNA antibodies have been explored in greater depth as a therapeutic target in the management of SLE. A substantial amount of data indicates that blockade of pathogenic anti-dsDNA antibodies can prevent or even reverse organ damage in murine models of SLE. This review focuses on the recent research advances regarding the origin, specificity, classification, and pathogenicity of anti-dsDNA antibodies and highlights the emerging therapies associated with them.

cThe Chinese virulent (CHv) strain of duck enteritis virus (DEV) has a genome of approximately 162,175 nucleotides with a GC content of 44.89%. Here we report the complete genomic sequence and annotation of DEV CHv, which offer an effective platform for providing authentic research experiences to novice scientists. In addition, knowledge of this virus will extend our general knowledge of DEV and will be useful for further studies of the mechanisms of virus replication and pathogenesis. D uck viral enteritis (DVE) is an acute, septic, contagious, and lethal disease that attacks ducks, geese, swans, and other members of the family Anatidae, order Anseriformes (6). The first known occurrence of DVE in the world was a major outbreak in the Netherlands in 1923 (1), and the first instance of DVE in China was reported in 1957. Nowadays, it is one of the most widespread and devastating diseases of waterfowl in the Anatidae family and has severely affected the waterfowl industry because of its relatively high mortality and wide host range.Duck enteritis virus (DEV) is the causative agent of DVE and was alternatively known as anatid herpesvirus 1 (AnHV-1) and duck plague virus (DPV). It has been clustered in the Alphaherpesvirinae subfamily, according to the eighth report of the International Committee on Taxonomy of Viruses (ICTV) (3). DEV may be closely related to mardiviruses, but it has not yet been classified in any genus. Lack of a genome sequence and genomic organization information is a factor that limits DEV taxonomy. Here we report the complete genomic sequence of the DEV Chinese virulent strain (CHv), which was isolated from infected ducks that showed a characteristic hemorrhagic button or bandlike lesions on the mucosal surface of the intestines.Construction of the library and sequencing of the DEV genome were performed as previously described (2). Considering the tandem duplication pattern of the DEV genome (5), we amplified the 5= and 3= ends of the DEV genome using a pair of primers. The shotgun library was sequenced and assembled.The DEV genome is linear, double-stranded DNA which consists of two covalently linked components, designated unique long (UL) and unique short (US), with each component consisting of unique sequences bracketed by the internal and terminal inverted repeat sequences (IRS and TRS, respectively): UL-IRS-US-TRS. The 5=-untranslated region (UTR) is 5,686 bp in length and contains 25 TATA boxes, 8 CAAT boxes, 8 poly(A)s, and 1 GC box, while the corresponding component of 3= UTR has 3, 13, 4, and 7, respectively. All of them are regarded as potential transcriptional regulatory elements. Also, the 3= UTR possesses seven tandem repeats which can be defined as minisatellites, since the length of the repeat unit reaches up to 40 nt (4).A total of 78 ORFs were predicted to code the potential functional protein. Of these ORFs, 65 and 11 ORFs are located in the UL and US regions, respectively, whereas the remaining two (ICP4/IE180) are located completely in the IRS and TRS regions. It is worth n...

The antibiotic trimethoprim (TMP) is used to treat a variety of Escherichia coli infections, but its efficacy is limited by the rapid emergence of TMP-resistant bacteria. Previous laboratory evolution experiments have identified resistance-conferring mutations in the gene encoding the TMP target, bacterial dihydrofolate reductase (DHFR), in particular mutation L28R. Here, we show that 4’-desmethyltrimethoprim (4’-DTMP) inhibits both DHFR and its L28R variant, and selects against the emergence of TMP-resistant bacteria that carry the L28R mutation in laboratory experiments. Furthermore, antibiotic-sensitive E. coli populations acquire antibiotic resistance at a substantially slower rate when grown in the presence of 4’-DTMP than in the presence of TMP. We find that 4’-DTMP impedes evolution of resistance by selecting against resistant genotypes with the L28R mutation and diverting genetic trajectories to other resistance-conferring DHFR mutations with catalytic deficiencies. Our results demonstrate how a detailed characterization of resistance-conferring mutations in a target enzyme can help identify potential drugs against antibiotic-resistant bacteria, which may ultimately increase long-term efficacy of antimicrobial therapies by modulating evolutionary trajectories that lead to resistance.