The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report ...the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.
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•We generated a single-cell atlas of PBMCs in both COVID-19 and influenza patients•Plasma cells increase significantly in both COVID-19 and influenza patients•COVID-19 is featured with XAF1-, TNF-, and FAS-induced T cell apoptosis•COVID-19 activates distinct pathway (STAT1/IRF3) versus influenza (STAT3/NFκB)
COVID-19 and influenza are both respiratory infections with cytokine release syndrome. Zhu et al. use single-cell RNA sequencing of longitudinally collected PBMCs in both patients to reveal distinct immune response landscapes of the two diseases and identify virus-specific cell composition and immune response pathways.
Rapid detection of highly contagious pathogens is the key to increasing the probability of survival and reducing infection rates. We developed a sensitive and quantitative lateral flow assay for ...detection of Ebola virus (EBOV) glycoprotein with a novel multifunctional nanosphere (RNs@Au) as a reporter. Each RNs@Au contains hundreds of quantum dots and dozens of Au nanoparticles and can achieve enhanced dual-signal readout (fluorescence signal for quantitative detection and colorimetric signal for visual detection). Antibody (Ab) and streptavidin (SA) were simultaneously modified onto the RNs@Au to label the target and act as signal enhancer. After the target was labeled by the Ab–RNs@Au–SA and captured on the test line, biotin-modified RNs@Au was used to amplify the dual signal by the reaction of SA with biotin. The assay enables naked-eye detection of 2 ng/mL glycoprotein within 20 min, and the quantitative detection limit is 0.18 ng/mL. Additionally, the assay has been successfully tested in field work for detecting EBOV in spiked urine, plasma, and tap water samples and is thus a promising candidate for early diagnosis of suspect infections in EBOV-stricken areas.
RIG-I is a key cytosolic pattern recognition receptor that interacts with MAVS to induce type I interferons (IFNs) against RNA virus infection. In this study, we found that cyclophilin A (CypA), a ...peptidyl-prolyl
isomerase, functioned as a critical positive regulator of RIG-I-mediated antiviral immune responses. Deficiency of CypA impaired RIG-I-mediated type I IFN production and promoted viral replication in human cells and mice. Upon Sendai virus infection, CypA increased the interaction between RIG-I and its E3 ubiquitin ligase TRIM25, leading to enhanced TRIM25-mediated K63-linked ubiquitination of RIG-I that facilitated recruitment of RIG-I to MAVS. In addition, CypA and TRIM25 competitively interacted with MAVS, thereby inhibiting TRIM25-induced K48-linked ubiquitination of MAVS. Taken together, our findings reveal an essential role of CypA in boosting RIG-I-mediated antiviral immune responses by controlling the ubiquitination of RIG-I and MAVS.
Antibiotic-resistant pathogens pose high risks to human and animal health worldwide. In recent years, the role of gut microbiota as a reservoir of antibiotic resistance genes (ARGs) in humans and ...animals has been increasingly investigated. However, the structure and function of the gut bacterial community, as well as the ARGs they carry in migratory birds remain unknown.
Here, we collected samples from migratory bird species and their associated environments and characterized their gut microbiomes and resistomes using shotgun metagenomic sequencing. We found that migratory birds vary greatly in gut bacterial composition but are similar in their microbiome metabolism and function. Birds from the same environment tend to harbor similar bacterial communities. In total, 1030 different ARGs (202 resistance types) conferring resistance to tetracycline, aminoglycoside, β-lactam, sulphonamide, chloramphenicol, macrolide-lincosamide-streptogramin (MLS), and quinolone are identified. Procrustes analysis indicated that microbial community structure is not correlated with the resistome in migratory birds. Moreover, metagenomic assembly-based host tracking revealed that most of the ARG-carrying contigs originate from Proteobacteria. Co-occurrence patterns revealed by network analysis showed that emrD, emrY, ANT(6)-Ia, and tetO, the hubs of ARG type network, are indicators of other co-occurring ARG types. Compared with the microbiomes and resistomes in the environment, migratory birds harbor a lower phylogenetic diversity but have more antibiotic resistance proteins. Interestingly, we found that the mcr-1 resistance gene is widespread among different birds, accounting for 50% of the total samples. Meanwhile, a large number of novel β-lactamase genes are also reconstructed from bird metagenomic assemblies based on fARGene software.
Our study provides a comprehensive overview of the diversity and abundance of ARGs in migratory birds and highlights the possible role of migratory birds as ARG disseminators into the environment. Video abstract.
•More diversified ARGs were identified the LPMs than the farms.•The live poultry trade may speed up the spread of antibiotic resistance.•LPM workers are exposed to antimicrobial resistant bacteria in ...LPMs.•More abundant ARGs were observed in the LPM workers than control subjects.•The prevalence of mcr-1 decreased significantly in LPMs after the ban on colistin as a growth promoter.
Poultry farms and LPMs are a reservoir of antimicrobial resistant bacteria and resistance genes from feces. The LPM is an important interface between humans, farm animals, and environments in a typical urban environment, and it is considered a reservoir for ARGs and viruses. However, the antibiotic resistomes shared between chicken farms and LPMs, and that of LPM workers and people who have no contact with the LPMs remains unknown.
We characterized the resistome and bacterial microbiome of farm chickens and LPMs and LPM workers and control subjects. The mobile ARGs identified in chickens and the distribution of the mcr-family genes in publicly bacterial genomes and chicken gut metagenomes was analyzed, respectively. In addition, the prevalence of mcr-1 in LPMs following the ban on colistin-positive additives in China was explored.
By profiling the microbiomes and resistomes in chicken farms, LPMs, LPM workers, and LPM environments, we found that the bacterial community composition and resistomes were significantly different between the farms and the LPMs, and the LPM samples possessed more diversified ARGs (59 types) than the farms. Some mobile ARGs, such as mcr-1 and tet(X3), identified in chicken farms, LPMs, LPM workers, and LPM environments were also harbored by human clinical pathogens. Moreover, we found that the resistomes were significantly different between the LPM workers and those who have no contact with the LPMs, and more diversified ARGs (188 types) were observed in the LPM workers. It is also worth noting that mcr-10 was identified in both human (5.2%, 96/1,859) and chicken (1.5%, 14/910) gut microbiomes. Although mcr-1 prevalence decreased significantly in the LPMs across the eight provinces in China, from 190/333 (57.1%) samples in September 2016-March 2017 to 208/544 (38.2%) samples in August 2018-May 2019, it is widespread and continuous in the LPMs.
Live poultry trade has a significant effect on the diversity of ARGs in LPM workers, chickens, and environments in China, driven by human selection with the live poultry trade. Our findings highlight the live poultry trade as ARG disseminators into LPMs, which serve as an interface of LPM environments even LPM workers, and that could urge Government to have better control of LPMs in China. Further studies on the factors that promote antibiotic resistance exchange between LPM environments, human commensals, and pathogens, are warranted.
In May 2016, a highly pathogenic avian influenza A(H5N8) virus strain caused deaths among 3 species of wild migratory birds in Qinghai Lake, China. Genetic analysis showed that the novel reassortant ...virus belongs to group B H5N8 viruses and that the reassortment events likely occurred in early 2016.
First reported in September, 2012, human infections with Middle East respiratory syndrome coronavirus (MERS-CoV) can result in severe respiratory disease, characterised by life-threatening pneumonia ...and renal failure.1 Countries with primary infections of MERS-CoV are located in the Middle East, but cases have been occasionally exported in other countries (figure).
SARS-CoV-2 is the cause of the current global pandemic of COVID-19; this virus infects multiple organs, such as the lungs and gastrointestinal tract. The microbiome in these organs, including the ...bacteriome and virome, responds to infection and might also influence disease progression and treatment outcome. In a cohort of 13 COVID-19 patients in Beijing, China, we observed that the gut virome and bacteriome in the COVID-19 patients were notably different from those of five healthy controls. We identified a bacterial dysbiosis signature by observing reduced diversity and viral shifts in patients, and among the patients, the bacterial/viral compositions were different between patients of different severities, although these differences are not entirely distinguishable from the effect of antibiotics. Severe cases of COVID-19 exhibited a greater abundance of opportunistic pathogens but were depleted for butyrate-producing groups of bacteria compared with mild to moderate cases. We replicated our findings in a mouse COVID-19 model, confirmed virome differences and bacteriome dysbiosis due to SARS-CoV-2 infection, and observed that immune/infection-related genes were differentially expressed in gut epithelial cells during infection, possibly explaining the virome and bacteriome dynamics. Our results suggest that the components of the microbiome, including the bacteriome and virome, are affected by SARS-CoV-2 infections, while their compositional signatures could reflect or even contribute to disease severity and recovery processes.
An avian-origin human-infecting influenza (H7N9) virus was recently identified in China. We have evaluated the viral hemagglutinin (HA) receptor-binding properties of two human H7N9 isolates, ...A/Shanghai/1/2013 (SH-H7N9) (containing the avian-signature residue Gln²²⁶) and A/Anhui/1/2013 (AH-H7N9) (containing the mammalian-signature residue Leu²²⁶). We found that SH-H7N9 HA preferentially binds the avian receptor analog, whereas AH-H7N9 HA binds both avian and human receptor analogs. Furthermore, an AH-H7N9 mutant HA (Leu²²⁶ → Gln) was found to exhibit dual receptor-binding property, indicating that other amino acid substitutions contribute to the receptor-binding switch. The structures of SH-H7N9 HA, AH-H7N9 HA, and its mutant in complex with either avian or human receptor analogs show how AH-H7N9 can bind human receptors while still retaining the avian receptor-binding property.
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