Stable Display of Artificially Long Foreign Antigens on Chimeric Bamboo mosaic virus Particles

Plant viruses can be genetically modified to generate chimeric virus particles (CVPs) carrying heterologous peptides fused on the surface of coat protein (CP) subunits as vaccine candidates. However, some factors may be especially significant in determining the properties of chimeras. In this study, peptides from various sources and of various lengths were inserted into the Bamboo mosaic virus-based (BaMV) vector CP N-terminus to examine the chimeras infecting and accumulating in plants. Interestingly, it was found that the two different strains Foot-and-mouth disease virus (FMDV) VP1 antigens with flexible linker peptides (77 or 82 amino acids) were directly expressed on the BaMV CP, and the chimeric particles self-assembled and continued to express FMDV antigens. The chimeric CP, when directly fused with a large foreign protein (117 amino acids), can self-fold into incomplete virus particles or disks. The physicochemical properties of heterologus peptides N-terminus, complex strand structures of heterologus peptides C-terminus and different flexible linker peptides, can affect the chimera accumulation. Based on these findings, using plant virus-based chimeras to express foreign proteins can increase their length limitations, and engineered plant-made CVP-based vaccines have increasing potential for further development as novel vaccines.

Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflects the Severity for the Acute and Chronic Infectious Diseases

Galectin-9 (Gal-9) is a β-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. We propose that FL-Gal-9 regulates the pathogenesis of infectious diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, and tuberculosis (TB). We also suggest that the blood levels of FL-Gal-9 reflect the severity of dengue, malaria, and HIV/OI, and those of Tr-Gal-9 markedly reflect the severity of HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was suggested to be an indicator of respiratory failure from coronavirus disease 2019 (COVID-19) as well as useful for differentiating pulmonary from extrapulmonary TB. The protease cleavage of FL-Gal-9 may lead to uncontrolled hyper-immune activation, including a cytokine storm. In summary, Gal-9 has potential to reflect the disease severity for the acute and chronic infectious diseases.

The Coevolution of Phycobilisomes: Molecular Structure Adapting to Functional Evolution

Phycobilisome is the major light-harvesting complex in cyanobacteria and red alga. It consists of phycobiliproteins and their associated linker peptides which play key role in absorption and unidirectional transfer of light energy and the stability of the whole complex system, respectively. Former researches on the evolution among PBPs and linker peptides had mainly focused on the phylogenetic analysis and selective evolution. Coevolution is the change that the conformation of one residue is interrupted by mutation and a compensatory change selected for in its interacting partner. Here, coevolutionary analysis of allophycocyanin, phycocyanin, and phycoerythrin and covariation analysis of linker peptides were performed. Coevolution analyses reveal that these sites are significantly correlated, showing strong evidence of the functional and structural importance of interactions among these residues. According to interprotein coevolution analysis, less interaction was found between PBPs and linker peptides. Our results also revealed the correlations between the coevolution and adaptive selection in PBS were not directly related, but probably demonstrated by the sites coupled under physical-chemical interactions.