Biosafety and Health最新文献

West Nile virus (WNV) is a mosquito-transmitted flavivirus distributed globally for decades and can cause disease in humans and animals. So far, no WNV vaccine has been licensed for human use. Therefore, the development of novel candidate vaccines and the improvement of vaccination strategies is imperative. As the WNV envelope (E) glycoprotein plays an important role in mediating viral binding to cellular receptors and virus-cell membrane fusion, it is a critical target for the host humoral response. Here, we prepared a recombinant truncated envelope protein of WNV (rWNV-80E) and developed a WNV subunit vaccine formulation with a combination of aluminum hydroxide (alum) and a synthetic oligonucleotide CpG as adjuvants. C57BL/6 mice were immunized twice intramuscularly at 28-day intervals with 5 µg purified rWNV-80E adjuvanted with Alum/CpG. WNV E-specific IgG was detected by enzyme-linked immunosorbent assay and neutralizing antibodies (nAbs) was detected using single-round infectious particles of WNV. Furthermore, T cell immunity was detected by enzyme-linked immunospot assay and intracellular cytokine staining assay. Notably, rWNV-80E was highly immunogenic and elicited potent humoral and cell immunity, as evidenced by significant levels of IFN-γ and TNF-α secretion in the T cells of mice. In summary, the Alum/CpG-adjuvanted rWNV-80E subunit vaccine elicited potent and balanced B- and T-cell immunity in mice, and therefore it is a promising candidate vaccine that warrants further investigation for use in human or veterinary applications.

During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activated macrophages, dendritic cells (D.C.), neutrophils, and natural killer (N.K.) cells are the first defense against infection. These immune effectors trap and ingest the virus, kill infected epithelial cells, or produce anti-viral cytokines. Evidence suggests that aging, obesity, and mental illness can lead to weakened innate immunity and, thus, are all associated with elevated infection and severe disease progression of coronavirus disease 2019 (COVID-19). Innate immune defense networks play a fundamental role in suppressing viral replication, infection establishment, and viral pathogenesis of SARS-CoV-2 and other respiratory viruses.

Recent studies suggested that cancer was a risk factor for coronavirus disease 2019 (COVID-19). Toll-like receptor 7 (TLR7), a severe acute respiratory syndrome 2 (SARS-CoV-2) virus's nucleic acid sensor, was discovered to be aberrantly expressed in many types of cancers. However, its expression pattern across cancers and association with COVID-19 has not been systematically studied. In this study, we proposed a computational framework to comprehensively study the roles of TLR7 in COVID-19 and pan-cancers at genetic, gene expression, protein, epigenetic, and single-cell levels. We found TLR7 mRNA expression was significantly up-regulated in 6 cancer types and down-regulated in 6 cancer types, further validated in the HPA database at the protein level. The genes significantly co-expressed with TLR7 were mainly enriched in the toll-like receptor signaling pathway, endolysosome, and signaling pattern recognition receptor activity. In addition, the abnormal TLR7 expression was associated with Mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB) in various cancers. Mined by the ESTIMATE algorithm, the expression of TLR7 was also closely linked to various immune infiltration patterns in pan-cancer, and TLR7 was mainly enriched in macrophages, as revealed by single-cell RNA sequencing. Finally, TLR7 expressions were very sensitive to a few targeted drugs, such as Alectinib and Imiquimod. In conclusion, TLR7 might be essential in the pathogenesis of COVID-19 and cancers.

The coronavirus disease 2019 (COVID-19) pandemic has dramatically increased the awareness of emerging infectious diseases. The advancement of multiomics analysis technology has resulted in the development of several databases containing virus information. Several scientists have integrated existing data on viruses to construct phylogenetic trees and predict virus mutation and transmission in different ways, providing prospective technical support for epidemic prevention and control. This review summarized the databases of known emerging infectious viruses and techniques focusing on virus variant forecasting and early warning. It focuses on the multi-dimensional information integration and database construction of emerging infectious viruses, virus mutation spectrum construction and variant forecast model, analysis of the affinity between mutation antigen and the receptor, propagation model of virus dynamic evolution, and monitoring and early warning for variants. As people have suffered from COVID-19 and repeated flu outbreaks, we focused on the research results of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses. This review comprehensively viewed the latest virus research and provided a reference for future virus prevention and control research.

Human enterovirus (EV) infections can lead to various manifestations, with variable correlations between genotypes and symptoms. Human enterovirus D68 (EV-D68) was considered to be associated with acute respiratory disease and acute flaccid myelitis. In this short report, both EV-D68 and poliovirus 3 were detected in the stool of a hospitalized 5-month child who presented with acute respiratory symptoms and who was recently vaccinated with oral polio vaccine (OPV), using a metatranscriptomic high-throughput sequencing method. The nearly full-length genome sequences with complete open reading frames of EV-D68 and poliovirus 3 were assembled. One previously-reported neurovirulence-related amino acid substitution (T860N) in the EV-D68 VP1 region was observed, but the patient showed no neurological symptoms. More attention should be paid to EV-D68, and continuous multiple syndrome-based surveillance on non-polio enterovirus is called for.

Environmental surveillance (ES) is a useful approach for monitoring circulating viruses, including polioviruses (PVs) and non-polio enteroviruses (NPEVs). In this study, the results of nine years of ES from 2013 to 2021 at six sampling sites in three cities in Fujian Province, China, were summarized. It showed that the sewage samples contained abundant viruses, but the positive rate was affected by different sampling sites. From the 520 samples, 431 PVs, 1,713 NPEVs, and 281 human adenoviruses (HAdVs) were isolated. PV isolates had been markedly affected following the adjustment of the immunization strategy. All but one PV isolate were Sabin-like strains without wild PVs. One isolate was vaccine-derived PV type 3 with 10 variation points in the VP1 region. After May 2016, PV type 2 was no longer detected, and PV type 3 became a superior serotype. Of 1,713 NPEVs, 24 serotypes were identified, including echovirus11 (E11), E6, coxsackievirus B3 (CVB3), CVB5, E7, and E3 were the predominant serotypes (37.65%, 20.96%, 11.50%, 8.87%, 8.23%, and 7.06%, respectively). The temporal dynamic of the six common serotypes was inconsistent. E3 was frequently isolated, but the number of isolates was low, with no obvious peaks. E6, E7, and CVB3 exhibited periodic changes with a high peak every three to four years, and E11 only had one high peak lasting four years. Summer-fall peaks of the echoviruses and spring-winter peaks of CVB were observed in the monthly distribution of virus isolation. The infectious isolates of various serotypes of different species identified from the sewage samples showed that ES is an essential part of pathogen surveillance.

Genome data of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for virus diagnosis, vaccine development, and variant surveillance. To archive and integrate worldwide SARS-CoV-2 genome data, a series of resources have been constructed, serving as a fundamental infrastructure for SARS-CoV-2 research, pandemic prevention and control, and coronavirus disease 2019 (COVID-19) therapy. Here we present an overview of extant SARS-CoV-2 resources that are devoted to genome data deposition and integration. We review deposition resources in data accessibility, metadata standardization, data curation and annotation; review integrative resources in data source, de-redundancy processing, data curation and quality assessment, and variant annotation. Moreover, we address issues that impede SARS-CoV-2 genome data integration, including low-complexity, inconsistency and absence of isolate name, sequence inconsistency, asynchronous update of genome data, and mismatched metadata. We finally provide insights into data standardization consensus and data submission guidelines, to promote SARS-CoV-2 genome data sharing and integration.

Enteroviruses (EVs) are classified into 15 species according to their sequence diversity. They include four human EV (A, B, C, and D) and three rhinoviruses (A, B, and C), and cause diseases in millions of people worldwide. Generally, individuals with enteroviral infections have mild clinical symptoms, including respiratory illness, vomiting, diarrhea, dizziness, and fever. More importantly, some members of the human EV family are neurotropic pathogens that may cause a wide range of clinical diseases, such as aseptic meningitis and encephalitis. Previously, the EV that caused the most severe neurotropic symptoms was poliovirus (PV), a member of the EV C group. Poliovirus has been eliminated in most countries through a global vaccination campaign. Non-PV EVs infect the central nervous system (CNS) and are the major EVs causing neurological diseases. These human non-PV EVs include EV A (e.g., EV-A71, CVA6, and CVA16), B (e.g., CVA9 and CVB3, CVB5, echovirus 11 [E11], E30, and E7), C (e.g., CVA24), and D (e.g., EV-D68). Here, we review the relationship between EV infection and CNS diseases and advance in the use of cellular receptors and host immune responses during viral infection.

The objective of this study was to investigate the outbreak of echovirus 11 (ECHO 11) infection in newborns at a hospital in Guangdong Province, China, and to study the effectiveness of prevention and control measures to infer the epidemiological characteristics of ECHO 11 and explore the effective measures for its prevention and control. We performed retrospective analyses of hospital records and laboratory test data. In this outbreak, ten cases of ECHO 11 infection were identified, of which nine cases were nosocomial infections. Most of the cases (90%) were severe, and three died. The onset time interval of 10 patients was 1–4 days, most of which occur in 1–2 days. There were eight (80%) males and two females (20%). The gestational age of the patients was 31 to 40 weeks (mean, 35⁺⁴ weeks; median, 35⁺⁴ weeks). The onset time was 3–26 days (average 9 days; median 8 days). The birth weights of the patients ranged from 1,650 g to 3,450 g (mean 2,385 g; median 2,250 g). We concluded that neonatal infection with ECHO 11 will lead to serious symptoms and high mortality, and is prone to outbreaks of nosocomial infection. We speculate that ECHO 11 is most likely to spread via contact transmission; however, we do not rule out the possibility of droplet transmission. Prevention and control measures can effectively prevent and control hospital enteroviral infections.