Phylogenetic diversity and functional potential of large and cell-associated viruses in the Bay of Bengal.

IMPORTANCE: The BoB, the world's largest bay, is of significant economic importance to surrounding countries, particularly Bangladesh, which heavily relies on its coastal resources. Concurrently, the BoB holds substantial ecological relevance due to the region's high vulnerability to climate change-induced impacts. Yet, our understanding of the BoB's microbiome in relation to marine food web and biogeochemical cycling remains limited. Particularly, there are little or no data on the viral diversity and host association in the BoB. We examined the viral community in two distinct BoB coastal regions to reveal a multitude of viral species interacting with a wide range of microbial hosts, some of which play key roles in coastal biogeochemical cycling or potential pathogens. Furthermore, we demonstrate that the BoB coast harbors a diverse community of large and giant viruses, underscoring the importance of investigating understudied environments to discover novel viral lineages with complex metabolic capacities.

U.S. kills effort to hunt dangerous viruses.

Critics feared DEEP VZN project could help pathogens jump from animals to humans.

Multimodal metagenomic analysis reveals microbial single nucleotide variants as superior biomarkers for early detection of colorectal cancer.

Microbial signatures show remarkable potentials in predicting colorectal cancer (CRC). This study aimed to evaluate the diagnostic powers of multimodal microbial signatures, multi-kingdom species, genes, and single-nucleotide variants (SNVs) for detecting precancerous adenomas. We performed cross-cohort analyses on whole metagenome sequencing data of 750 samples via xMarkerFinder to identify adenoma-associated microbial multimodal signatures. Our data revealed that fungal species outperformed species from other kingdoms with an area under the ROC curve (AUC) of 0.71 in distinguishing adenomas from controls. The microbial SNVs, including dark SNVs with synonymous mutations, displayed the strongest diagnostic capability with an AUC value of 0.89, sensitivity of 0.79, specificity of 0.85, and Matthews correlation coefficient (MCC) of 0.74. SNV biomarkers also exhibited outstanding performances in three independent validation cohorts (AUCs = 0.83, 0.82, 0.76; sensitivity = 1.0, 0.72, 0.93; specificity = 0.67, 0.81, 0.67, MCCs = 0.69, 0.83, 0.72) with high disease specificity for adenoma. In further support of the above results, functional analyses revealed more frequent inter-kingdom associations between bacteria and fungi, and abnormalities in quorum sensing, purine and butanoate metabolism in adenoma, which were validated in a newly recruited cohort via qRT-PCR. Therefore, these data extend our understanding of adenoma-associated multimodal alterations in the gut microbiome and provide a rationale of microbial SNVs for the early detection of CRC.

Improvement of Sensitivity and Speed of Virus Sensing Technologies Using nm- and µm-Scale Components.

Various viral diseases can be widespread and cause severe disruption to global society. Highly sensitive virus detection methods are needed to take effective measures to prevent the spread of viral infection. This required the development of rapid virus detection technology to detect viruses at low concentrations, even in the biological fluid of patients in the early stages of the disease or environmental samples. This review describes an overview of various virus detection technologies and then refers to typical technologies such as beads-based assay, digital assay, and pore-based sensing, which are the three modern approaches to improve the performance of viral sensing in terms of speed and sensitivity.

Laboratory assessment of a multi-target assay for the rapid detection of viruses causing vesicular diseases.

BACKGROUND: The recent mpox outbreak has highlighted the need to rapidly diagnose the causative agents of viral vesicular disease to inform treatment and control measures. Common causes of vesicular disease include Monkeypox virus (MPXV), clades I and II, Herpes simplex viruses Type 1 and Type 2 (HSV-1, HSV-2), human herpes virus 6 (HHV-6), Varicella-zoster virus (VZV) and Enteroviruses (EVs). Here, we assessed a syndromic viral vesicular panel for rapid and simultaneous detection of these 7 targets in a single cartridge. OBJECTIVE: The aim of this study was to evaluate the QIAStat-Dx ® viral vesicular (VV) panel and compare with laboratory developed tests (LDTs). Limit of detection, inter-run variability, cross-reactivity and specificity were assessed. Positive and negative percent agreement, and correlation between assays was determined using 124 clinical samples from multiple anatomical sites. RESULTS: The overall concordance between the QIAstat and LDTs was 96%. Positive percent agreement was 82% for HHV-6, 89% for HSV-1 and 100% for MPXV, HSV-2, EV and VZV. Negative percent agreement was 100% for all targets assessed. There was no cross-reactivity with Vaccinia, Orf, Molluscum contagiosum viruses, and a pooled respiratory panel. CONCLUSION: The QIAstat VV multi-target syndromic panel combine ease of use, rapid turnaround, good sensitivity and specificity for enhanced diagnosis, clinical care and public health responses.

Identifying animal viruses in humans.

Experimental virology can inform strategic monitoring for new viruses in humans.

Virus hunters test new surveillance tools.

Ropes, drones, insects, and dust cloths could make monitoring faster, safer, and cheaper.

Age-dependent nasal immune responses in non-hospitalized bronchiolitis children.

Bronchiolitis in children is associated with significant rates of morbidity and mortality. Many studies have been performed using samples from hospitalized bronchiolitis patients, but little is known about the immunological responses from infants suffering from mild/moderate bronchiolitis that do not require hospitalization. We have studied a collection of nasal lavage fluid (NLF) samples from outpatient bronchiolitis children as a novel strategy to unravel local humoral and cellular responses, which are not fully characterized. The children were age-stratified in three groups, two of them (GI under 2-months, GII between 2-4 months) presenting a first episode of bronchiolitis, and GIII (between 4 months and 2 years) with recurrent respiratory infections. Here we show that elevated levels of pro-inflammatory cytokines (IL1ß, IL6, TNFα, IL18, IL23), regulatory cytokines (IL10, IL17A) and IFNγ were found in the three bronchiolitis cohorts. However, little or no change was observed for IL33 and MCP1, at difference to previous results from bronchiolitis hospitalized patients. Furthermore, our results show a tendency to IL1ß, IL6, IL18 and TNFα increased levels in children with mild pattern of symptom severity and in those in which non RSV respiratory virus were detected compared to RSV+ samples. By contrast, no such differences were found based on gender distribution. Bronchiolitis NLFs contained more IgM, IgG1, IgG3 IgG4 and IgA than NLF from their age-matched healthy controls. NLF from bronchiolitis children predominantly contained neutrophils, and also low frequency of monocytes and few CD4+ and CD8+ T cells. NLF from infants older than 4-months contained more intermediate monocytes and B cell subsets, including naïve and memory cells. BCR repertoire analysis of NLF samples showed a biased VH1 usage in IgM repertoires, with low levels of somatic hypermutation. Strikingly, algorithmic studies of the mutation profiles, denoted antigenic selection on IgA-NLF repertoires. Our results support the use of NLF samples to analyze immune responses and may have therapeutic implications.

Características radiográficas de la neumonía adquirida en la comunidad en el adulto inmunocompetente hospitalizado según el agente causal / Radiographic characteristics of community-acquired pneumonia in the immunocompetent adult hospitalized according to the etiologic agent

Resumen En la práctica clínica, la radiografía de tórax permite confirmar el diagnóstico y la extensión de la neumonía adquirida en la comunidad (NAC). Objetivos: Examinar las características radiográficas de la NAC según el agente causal y el grado de concordancia interobservador (CI) en la descripción de los hallazgos radiográficos. Métodos: Se evaluaron las radiografías de tórax de 300 pacientes adultos inmunocompetentes hospitalizados por NAC, tres residentes de radiología consignaron el patrón de los infiltrados pulmonares, su localización anatómica y extensión, la presencia de derrame pleural y otros hallazgos radiográficos. Se realizaron cultivos de esputo, hemocultivos, pruebas serológicas y técnicas de biología molecular de hisopado nasofaríngeo para identificar los principales patógenos respiratorios. Resultados: Las manifestaciones clínicas y los hallazgos de la radiografía de tórax fueron similares en las neumonías causadas por diferentes patógenos respiratorios: bacterias clásicas, virus respiratorios y microorganismos atípicos. En las neumonías bacterianas predominó el patrón de relleno alveolar de distribución lobar, en las neumonías vírales y atípicas predominó el patrón intersticial o mixto alvéolo-intersticial con opacidades en vidrio esmerilado. La CI fue satisfactoria (kappa > 0,6) para determinar el patrón principal de los infiltrados pulmonares, su localización anatómica y la presencia de derrame pleural, su localización y extensión. La CI fue moderada (kappa 0,4-0,6) para definir la extensión de la neumonía y detectar signos radiológicos asociados a congestión pulmonar. Conclusión: Los hallazgos de la radiografía de tórax no permitieron identificar con precisión el agente causal de la neumonía, siendo útil en la caracterización de los infiltrados pulmonares y para detectar complicaciones como el derrame paraneumónico.

In a clinical setting the chest radiograph is the reference standard in establishing the diagnosis of community-acquired pneumonia (CAP). Objectives: This study aimed to assess interobserver reliability (IR) of radiographic findings and the relationship to different respiratory pathogens in CAP. Methods: Chest radiographs of 300 immunocompetent adult patients hospitalized with pneumonia, obtained from a database, were reviewed by three residents of radiology without specific clinical information. Main pattern of pulmonary infiltrates, topographic localization, extent of pneumonia, presence of pleural fluid, thickened bronchial walls, lymphadenopathy and air bronchogram were scored. Sputum and blood cultures, serological tests and nasopharyngeal swab for respiratory virus detection by molecular diagnostic techniques were performed to identify the causative pathogen. Results: Clinical manifestations and chest X-ray findings were similar in pneumonias caused by different respiratory pathogens: classic bacteria, respiratory viruses and atypical microorganisms. The alveolar pattern of lobar distribution predominated in bacterial pneumonia; meanwhile, interstitial or mixed alveolar-interstitial pattern with ground glass opacities predominated in viral and atypical pneumonias. IR was fair to good (kappa > 0.6) for determining the main pattern of infiltrates, anatomical location and the presence of pleural effusion, their anatomical location and extension. IR was moderate (kappa 0.4-0.6) for determining the extent of pneumonia and signs of congestive heart failure. Conclusion: Simple features such as main pattern description, anatomical location, identifying the involved lobes and pleural fluid recognition showed fair to excellent interobserver reliability. Chest radiographs was of limited value in predicting the causative pathogen but were of beneficial use to characterize pulmonary infiltrates and to detect complications such as parapneumonic effusion.

Climate change increases cross-species viral transmission risk.

At least 10,000 virus species have the ability to infect humans but, at present, the vast majority are circulating silently in wild mammals1,2. However, changes in climate and land use will lead to opportunities for viral sharing among previously geographically isolated species of wildlife3,4. In some cases, this will facilitate zoonotic spillover-a mechanistic link between global environmental change and disease emergence. Here we simulate potential hotspots of future viral sharing, using a phylogeographical model of the mammal-virus network, and projections of geographical range shifts for 3,139 mammal species under climate-change and land-use scenarios for the year 2070. We predict that species will aggregate in new combinations at high elevations, in biodiversity hotspots, and in areas of high human population density in Asia and Africa, causing the cross-species transmission of their associated viruses an estimated 4,000 times. Owing to their unique dispersal ability, bats account for the majority of novel viral sharing and are likely to share viruses along evolutionary pathways that will facilitate future emergence in humans. Notably, we find that this ecological transition may already be underway, and holding warming under 2 °C within the twenty-first century will not reduce future viral sharing. Our findings highlight an urgent need to pair viral surveillance and discovery efforts with biodiversity surveys tracking the range shifts of species, especially in tropical regions that contain the most zoonoses and are experiencing rapid warming.

A Lab-in-a-Fiber optofluidic device using droplet microfluidics and laser-induced fluorescence for virus detection.

Microfluidics has emerged rapidly over the past 20 years and has been investigated for a variety of applications from life sciences to environmental monitoring. Although continuous-flow microfluidics is ubiquitous, segmented-flow or droplet microfluidics offers several attractive features. Droplets can be independently manipulated and analyzed with very high throughput. Typically, microfluidics is carried out within planar networks of microchannels, namely, microfluidic chips. We propose that fibers offer an interesting alternative format with key advantages for enhanced optical coupling. Herein, we demonstrate the generation of monodisperse droplets within a uniaxial optofluidic Lab-in-a-Fiber scheme. We combine droplet microfluidics with laser-induced fluorescence (LIF) detection achieved through the development of an optical side-coupling fiber, which we term a periscope fiber. This arrangement provides stable and compact alignment. Laser-induced fluorescence offers high sensitivity and low detection limits with a rapid response time making it an attractive detection method for in situ real-time measurements. We use the well-established fluorophore, fluorescein, to characterize the Lab-in-a-Fiber device and determine the generation of [Formula: see text] 0.9 nL droplets. We present characterization data of a range of fluorescein concentrations, establishing a limit of detection (LOD) of 10 nM fluorescein. Finally, we show that the device operates within a realistic and relevant fluorescence regime by detecting reverse-transcription loop-mediated isothermal amplification (RT-LAMP) products in the context of COVID-19 diagnostics. The device represents a step towards the development of a point-of-care droplet digital RT-LAMP platform.

Virus clearance by activated carbon for therapeutic monoclonal antibody purification.

In our previous study, activated carbon (AC) was employed in the purification process of therapeutic monoclonal antibody (mAb) as a replacement for Protein A affinity chromatography. In addition, we established an innovative column-free flow-through purification process using AC filter. In these investigations, the effective clearance of impurities (high-molecular-weight species, low-molecular-weight species, host cell proteins, and DNA) was observed compared to the conventional Protein A platform purification process. In this study, virus removal capability of our established AC process (AC filter) was investigated using two model viruses, Murine Leukemia Virus (MuLV) and Minute Virus of Mice (MVM) with the combination of two filtration methods (single-pass filtration and re-circulation filtration) using three kinds of mAbs. We found effective clearance of both MuLV and MVM (>3 log reduction factor, LRF) in all mAbs. Not only filtration method but also re-circulation duration didn't affect LRF, and >3 LRF of virus removal could be achieved by only single-pass filtration. From these results, it is expected that AC will be a promising candidate for the virus removal unit operation for mAb purification processes.

A genome-wide association study in a large community-based cohort identifies multiple loci associated with susceptibility to bacterial and viral infections.

There is limited data on host-specific genetic determinants of susceptibility to bacterial and viral infections. Genome-wide association studies using large population cohorts can be a first step towards identifying patients prone to infectious diseases and targets for new therapies. Genetic variants associated with clinically relevant entities of bacterial and viral infections (e.g., abdominal infections, respiratory infections, and sepsis) in 337,484 participants of the UK Biobank cohort were explored by genome-wide association analyses. Cases (n = 81,179) were identified based on ICD-10 diagnosis codes of hospital inpatient and death registries. Functional annotation was performed using gene expression (eQTL) data. Fifty-seven unique genome-wide significant loci were found, many of which are novel in the context of infectious diseases. Some of the detected genetic variants were previously reported associated with infectious, inflammatory, autoimmune, and malignant diseases or key components of the immune system (e.g., white blood cells, cytokines). Fine mapping of the HLA region revealed significant associations with HLA-DQA1, HLA-DRB1, and HLA-DRB4 locus alleles. PPP1R14A showed strong colocalization with abdominal infections and gene expression in sigmoid and transverse colon, suggesting causality. Shared significant loci across infections and non-infectious phenotypes in the UK Biobank cohort were found, suggesting associations for example between SNPs identified for abdominal infections and CRP, rheumatoid arthritis, and diabetes mellitus. We report multiple loci associated with bacterial and viral infections. A better understanding of the genetic determinants of bacterial and viral infections can be useful to identify patients at risk and in the development of new drugs.

Inline-tandem purification of viruses from cell lysate by agarose-based chromatography.

An efficient chromatography-based virus purification method has been developed and validated for the non-pathogenic infectious virus PRD1. Compared to the conventional method that consists of relatively time-consuming and labour-intensive precipitation and density gradient ultracentrifugation steps, the method developed here is performed in a single flow using tandem-coupled anion exchange and size exclusion chromatography (AIEX-SEC) columns. This inline approach helps to minimize the loss of virus in the process and streamlines time consumption, since no physical transfer of the sample is required between purification steps. In the development process, sample feed composition, dynamic binding capacity and elution conditions for the AIEX resin as well as different exclusion limits for SEC resins were optimized to achieve maximal yield of pure infectious viruses. Utilizing this new approach, a high-quality virus sample was produced from a lysate feed in 320 min with a total yield of 13 mg purified particles per litre of cell lysate, constituting a 3.5-fold yield increase as compared to the conventional method, without compromising the high specific infectivity of the product (6 × 1012 to 7 × 1012 pfu/mg of protein). The yield of infectious viruses of the lysate feed was 54%. The easy scalability of chromatography-based methods provide a direct route to industrial usage without any significant changes needed to be made to the purification regime. This is especially interesting as the method has high potential to be used for purification of various viruses and nanoparticles, including adenovirus.

Aetiological Characteristics of Infectious Diarrhea in Yantai City, Shandong Province, China in 2017.

This study aimed to analyse the pathogenic spectrum and epidemiological characteristics of infectious diarrhea in Yantai City, Shandong Province, China and provide a reference for its prevention and control. A total of 713 stool specimens collected within 3 days of diarrhea onset from January to December 2017 at secondary or higher hospitals in Yantai City were tested for 10 causative pathogens, using real-time polymerase chain reaction (RT-PCR). The top two rotaviruses and norovirus were analysed for typing and geographical distribution. The total positive rate was 46.56% (332/713), and 268 of 713 specimens contained at least one pathogen; 64 had at least two pathogens, accounting for 19.28% of the positive specimens (64/332). The positivity rates of rotavirus (RV), norovirus (NoVs) GI, norovirus (NoVs) GII, enterovirus universal (EV), enteric adenoviruses (EAdV), sapovirus (SaV), astrovirus (Astv), Salmonella (SE), Listeria monocytogenes (LiMo), and Vibrio parahaemolyticus (VP) were 20.06% (143/713), 1.82% (13/713), 12.84% (89/713), 10.66% (76/713), 4.07% (29/713), 0.42% (3/713), 2.38% (17/713), 1.54% (11/713), 1.82% (13/713), and 1.54% (11/713), respectively. Infectious diarrhea showed a high prevalence in young children aged 1-5 years, accounting for 48.6% of the total number of cases. Bacterial diarrhea was predominant in summer, and viral diarrhea was distributed throughout the year, without a significant seasonal pattern. Rotavirus is dominated by G9P, accounting for 81.82%, while norovirus is dominated by the GII type and has diverse characteristics. The aetiology of infectious diarrhea in Yantai is mainly viral, with RV, NoVs, EV, EAdV, and Astv being the most frequent pathogens. Continuous surveillance of infectious diarrhea diseases can help us understand its epidemiological and pathogenic characteristics, thereby taking targeted preventive and control measures in different seasons.

Special Issue: Viral Infections in Companion Animals.

Companion animals, such as cats, dogs, horses and exotic species, play an important role in society; more than 600 million cats and 900 million dogs live closely with humans worldwide [...].

Ultrasensitive Aptasensors for the Detection of Viruses Based on Opto-Electrochemical Readout Systems.

Viral infections are becoming the foremost driver of morbidity, mortality and economic loss all around the world. Treatment for diseases associated to some deadly viruses are challenging tasks, due to lack of infrastructure, finance and availability of rapid, accurate and easy-to-use detection methods or devices. The emergence of biosensors has proven to be a success in the field of diagnosis to overcome the challenges associated with traditional methods. Furthermore, the incorporation of aptamers as bio-recognition elements in the design of biosensors has paved a way towards rapid, cost-effective, and specific detection devices which are insensitive to changes in the environment. In the last decade, aptamers have emerged to be suitable and efficient biorecognition elements for the detection of different kinds of analytes, such as metal ions, small and macro molecules, and even cells. The signal generation in the detection process depends on different parameters; one such parameter is whether the labelled molecule is incorporated or not for monitoring the sensing process. Based on the labelling, biosensors are classified as label or label-free; both have their significant advantages and disadvantages. Here, we have primarily reviewed the advantages for using aptamers in the transduction system of sensing devices. Furthermore, the labelled and label-free opto-electrochemical aptasensors for the detection of various kinds of viruses have been discussed. Moreover, numerous globally developed aptasensors for the sensing of different types of viruses have been illustrated and explained in tabulated form.