Background: The emergence of the novel, pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global health emergency. SARS-CoV-2 is highly contagious and has a high mortality rate in severe patients. However, there is very limited information on the effect of SARS-CoV-2 infection on the integrity of the blood–brain barrier (BBB). Methods: RNA-sequencing profiling was performed to analyze the transcriptomic changes in human brain microvascular endothelial cells (hBMECs) after SARS-CoV-2 infection. Bioinformatic tools were used for differential analysis. Immunofluorescence, real-time quantitative PCR, and Western blotting analysis were used to explore biological phenotypes. Results: A total of 927 differentially expressed genes were identified, 610 of which were significantly upregulated while the remaining 317 were downregulated. We verified the significant induction of cytokines, chemokines, and adhesion molecules in hBMECs by SARS-CoV-2, suggesting an activation of the vascular endothelium in brain. Moreover, we demonstrated that SARS-CoV-2 infection could increase the BBB permeability, by downregulating as well as remodeling the intercellular tight junction proteins. Conclusions: Our findings demonstrated that SARS-CoV-2 infection can cause BBB dysfunction, providing novel insights into the understanding of SARS-CoV-2 neuropathogenesis. Moreover, this finding shall constitute a new approach for future prevention and treatment of SARS-CoV-2-induced CNS infection.

Despite advances in supportive care and antimicrobial treatment, bacterial meningitis remains the most serious infection of the central nervous system (CNS) that poses a serious risk to life. This clinical dilemma is largely due to our insufficient knowledge of the pathology behind this disease. By controlling the entry of molecules into the CNS microenvironment, the blood–brain barrier (BBB), a highly selective cellular monolayer that is specific to the CNS’s microvasculature, regulates communication between the CNS and the rest of the body. A defining feature of the pathogenesis of bacterial meningitis is the increase in BBB permeability. So far, several contributing factors for BBB disruption have been reported, including direct cellular damage brought on by bacterial virulence factors, as well as host-specific proteins or inflammatory pathways being activated. Recent studies have demonstrated that targeting pathological factors contributing to enhanced BBB permeability is an effective therapeutic complement to antimicrobial therapy for treating bacterial meningitis. Hence, understanding how these meningitis-causing pathogens affect the BBB permeability will provide novel perspectives for investigating bacterial meningitis’s pathogenesis, prevention, and therapies. Here, we summarized the recent research progress on meningitis-causing pathogens disrupting the barrier function of BBB. This review provides handy information on BBB disruption by meningitis-causing pathogens, and helps design future research as well as develop potential combination therapies.

Neuroinflammation has been implicated in the initiation and progression of several central nervous system (CNS) disorders, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, ischemic stroke, traumatic brain injury, spinal cord injury, viral encephalitis, and bacterial encephalitis. Microglia and astrocytes are essential in neural development, maintenance of synaptic connections, and homeostasis in a healthy brain. The activation of astrocytes and microglia is a defense mechanism of the brain against damaged tissues and harmful pathogens. However, their activation triggers neuroinflammation, which can exacerbate or induce CNS injury. Non-coding RNAs (ncRNAs) are functional RNA molecules that lack coding capabilities but can actively regulate mRNA expression and function through various mechanisms. ncRNAs are highly expressed in astrocytes and microglia and are potential mediators of neuroinflammation. We reviewed the recent research progress on the role of miRNAs, lncRNAs, and circRNAs in regulating neuroinflammation in various CNS diseases. Understanding how these ncRNAs affect neuroinflammation will provide important therapeutic insights for preventing and managing CNS dysfunction.

Strains of extraintestinal pathogenic Escherichia coli (ExPEC) can invade and colonize extraintestinal sites and cause a wide range of infections. Genomic analysis of ExPEC has mainly focused on isolates of human and avian origins, with porcine ExPEC isolates yet to be sequenced. To better understand the genomic attributes underlying the pathogenicity of porcine ExPEC, we isolated two E. coli strains PCN033 and PCN061 from pigs, assessed their in vivo virulence, and completed and compared their genomes. Animal experiments demonstrated that strain PCN033, but not PCN061, was pathogenic in a pig model. The chromosome of PCN033 was 384 kb larger than that of PCN061. Among the PCN033-specific sequences, genes encoding adhesins, unique lipopolysaccharide, unique capsular polysaccharide, iron acquisition and transport systems, and metabolism were identified. Additionally, a large plasmid PCN033p3 harboring many typical ExPEC virulence factors was identified in PCN033. Based on the genetic variation between PCN033 and PCN061, corresponding phenotypic differences in flagellum-dependent swarming motility and metabolism were verified. Furthermore, the comparative genomic analyses showed that the PCN033 genome shared many similarities with genomic sequences of human ExPEC strains. Additionally, comparison of PCN033 genome with other nine characteristic E. coli genomes revealed 425 PCN033-special coding sequences. Genes of this subset included those encoding type I restriction-modification (R-M) system, type VI secretion system (T6SS) and membrane-associated proteins. The genetic and phenotypic differences between PCN033 and PCN061 could partially explain their differences in virulence, and also provide insight towards the molecular mechanisms of porcine ExPEC infections. Additionally, the similarities between the genomes of PCN033 and human ExPEC strains suggest that some connections between porcine and human ExPEC strains exist. The first completed genomic sequence for porcine ExPEC and the genomic differences identified by comparative analyses provide a baseline understanding of porcine ExPEC genetics and lay the foundation for their further study.

Pseudorabies virus (PRV) can infect most mammals and is well known for causing substantial economic losses in the pig industry. In addition to pigs, PRV infection usually leads to severe itching, central nervous system dysfunction, and 100% mortality in its non-natural hosts. It should be noted that increasing human cases of PRV infection have been reported in China since 2017, and these patients have generally suffered from nervous system damage and even death. Here, we reviewed the current prevalence and variation in PRV worldwide as well as the PRV-caused infections in animals and humans, and briefly summarized the vaccines and diagnostic methods used for pseudorabies control. Most countries, including China, have control programs in place for pseudorabies in domestic pigs, and thus, the disease is on the decline; however, PRV is still globally epizootic and an important pathogen for pigs. In countries where pseudorabies in domestic pigs have already been eliminated, the risk of PRV transmission by infected wild animals should be estimated and prevented. As a member of the alphaherpesviruses, PRV showed protein-coding variation that was relatively higher than that of herpes simplex virus-1 (HSV-1) and varicella-zoster virus (VZV), and its evolution was mainly contributed to by the frequent recombination observed between different genotypes or within the clade. Recombination events have promoted the generation of new variants, such as the variant strains resulting in the outbreak of pseudorabies in pigs in China, 2011. There have been 25 cases of PRV infections in humans reported in China since 2017, and they were considered to be infected by PRV variant strains. Although PRV infections have been sporadically reported in humans, their causal association remains to be determined. This review provided the latest epidemiological information on PRV for the better understanding, prevention, and treatment of pseudorabies.