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Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in young children and elderly, worldwide and poses significant risks to immunocompromised individuals. To elucidate host-virus interactions at the transcriptional level, we analyzed differential gene expression in HEp-2 cells infected with RSV using cDNA microarray analysis complemented by quantitative PCR (qPCR). HEp-2 cells were infected with RSV at a multiplicity of infection of 1, and total RNA was isolated 24 hours post-infection for gene expression profiling. Radiolabeled cDNA probes from RSV-infected and mock-infected cells were hybridized to Atlas ® Human Cancer cDNA arrays, and differential gene expression was quantified by densitometry. We identified 12 host genes that were significantly upregulated in RSV-infected cells from the cDNA microarray (≥2-fold increase, P <0.01), confirmed by qPCR, encompassing functional categories including cell cycle regulation, cytoskeletal organization, apoptosis modulation, immune evasion, and inflammation. Notably, the cyclin-dependent kinase inhibitor CDKN1A was induced ~14-fold, suggesting RSV triggers a host cell cycle arrest. The intermediate filament protein, vimentin was up ~6-fold, consistent with cytoskeletal rearrangements observed during viral syncytium formation. Anti-apoptotic MCL1 increased ~11-fold, while pro-apoptotic caspase-4 showed a more modest 1.6-fold rise, indicating a complex regulation of cell death pathways. We also observed marked upregulation of a fibronectin receptor subunit (~24-fold) and complement regulatory protein CD59 (~2-fold), highlighting potential mechanisms of enhanced cell-cell fusion and viral immune evasion. The proinflammatory cytokine interleukin-6 was elevated ~7-fold, underscoring the inflammatory response to RSV. These findings provide a global snapshot of the host transcriptomic response to RSV infection and yield insights into how RSV modulates host cellular machinery to favor viral replication and spread. Understanding these host-virus interactions may unveil novel targets for antiviral therapy and inform strategies to mitigate RSV disease pathogenesis.

Abstract The emergence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) reawakened the need to rapidly understand the molecular etiologies, pandemic potential, and prospective treatments of infectious agents. The lack of existing data on SARS-CoV-2 hampered early attempts to treat severe forms of coronavirus disease-2019 (COVID-19) during the pandemic. This study coupled existing transcriptomic data from severe acute respiratory syndrome-related coronavirus 1 (SARS-CoV-1) lung infection animal studies with crowdsourcing statistical approaches to derive temporal meta-signatures of host responses during early viral accumulation and subsequent clearance stages. Unsupervised and supervised machine learning approaches identified top dysregulated genes and potential biomarkers (e.g. CXCL10, BEX2, and ADM). Temporal meta-signatures revealed distinct gene expression programs with biological implications to a series of host responses underlying sustained Cxcl10 expression and Stat signaling. Cell cycle switched from G1/G0 phase genes, early in infection, to a G2/M gene signature during late infection that correlated with the enrichment of DNA damage response and repair genes. The SARS-CoV-1 meta-signatures were shown to closely emulate human SARS-CoV-2 host responses from emerging RNAseq, single cell, and proteomics data with early monocyte-macrophage activation followed by lymphocyte proliferation. The circulatory hormone adrenomedullin was observed as maximally elevated in elderly patients who died from COVID-19. Stage-specific correlations to compounds with potential to treat COVID-19 and future coronavirus infections were in part validated by a subset of twenty-four that are in clinical trials to treat COVID-19. This study represents a roadmap to leverage existing data in the public domain to derive novel molecular and biological insights and potential treatments to emerging human pathogens.

In the last decade, important discoveries have shown that resistance to reinfection can be achieved without a functional adaptive immune system, introducing the concept of innate immune memory in invertebrates. However, this field has been constrained by the limited number of molecular mechanisms evidenced to support these phenomena. Taking advantage of an invertebrate species, the Pacific oyster ( Crassostrea gigas ), in which we evidenced one of the longest and most effective periods of protection against viral infection observed in an invertebrate, we provide the first comprehensive transcriptomic analysis of antiviral innate immune priming. We show that priming with poly(I·C) induced a massive upregulation of immune-related genes, which control subsequent viral infection, and it was maintained for over 4 months after priming. This acquired resistant mechanism reinforces the molecular foundations of the sustained response model of immune priming. It opens the way to pseudovaccination to prevent the recurrent diseases that currently afflict economically or ecologically important invertebrates. Over the last decade, innate immune priming has been evidenced in many invertebrate phyla. If mechanistic models have been proposed, molecular studies aiming to substantiate these models have remained scarce. We reveal here the transcriptional signature associated with immune priming in the oyster Crassostrea gigas . Oysters were fully protected against Ostreid herpesvirus 1 (OsHV-1), a major oyster pathogen, after priming with poly(I·C), which mimics viral double-stranded RNA. Global analysis through RNA sequencing of oyster and viral genes after immune priming and viral infection revealed that poly(I·C) induces a strong antiviral response that impairs OsHV-1 replication. Protection is based on a sustained upregulation of immune genes, notably genes involved in the interferon pathway and apoptosis, which control subsequent viral infection. This persistent antiviral alert state remains active over 4 months and supports antiviral protection in the long term. This acquired resistance mechanism reinforces the molecular foundations of the sustained response model of immune priming. It further opens the way to applications (pseudovaccination) to cope with a recurrent disease that causes dramatic economic losses in the shellfish farming industry worldwide. IMPORTANCE In the last decade, important discoveries have shown that resistance to reinfection can be achieved without a functional adaptive immune system, introducing the concept of innate immune memory in invertebrates. However, this field has been constrained by the limited number of molecular mechanisms evidenced to support these phenomena. Taking advantage of an invertebrate species, the Pacific oyster ( Crassostrea gigas ), in which we evidenced one of the longest and most effective periods of protection against viral infection observed in an invertebrate, we provide the first comprehensive transcriptomic analysis of antiviral innate immune priming. We show that priming with poly(I·C) induced a massive upregulation of immune-related genes, which control subsequent viral infection, and it was maintained for over 4 months after priming. This acquired resistant mechanism reinforces the molecular foundations of the sustained response model of immune priming. It opens the way to pseudovaccination to prevent the recurrent diseases that currently afflict economically or ecologically important invertebrates.

Arbuscular mycorrhizal fungi (AMF) serve as both plant symbionts and allies in resisting pathogens and environmental stresses. Mycorrhizal colonization of plant roots can influence the outcomes of plant-pathogen interactions by enhancing specific host defense mechanisms. The transcriptional responses induced by AMF in virus-infected plants remain largely unexplored. In the presented study, we employed a comprehensive transcriptomic approach and qPCR to investigate the molecular determinants underlying the interaction between AMF and potato virus Y (PVY) in Solanum tuberosum L. Our primary goal was to identify the symbiosis- and defense-related determinants activated in mycorrhizal potatoes facing PVY. Through a comparative analysis of mRNA transcriptomes in experimental treatments comprising healthy and PVY-infected potatoes colonized by two AMF species, Rhizophagus regularis or Funneliformis mosseae, we unveiled the overexpression of genes associated with mycorrhiza, including nutrient exchange, lipid transfer, and cell wall remodeling. Furthermore, we identified several differentially expressed genes upregulated in all mycorrhizal treatments that encoded pathogenesis-related proteins involved in plant immune responses, thus verifying the bioprotective role of AMF. We investigated the relationship between mycorrhiza levels and PVY levels in potato leaves and roots. We found accumulation of the virus in the leaves of mycorrhizal plants, but our studies additionally showed a reduced PVY content in potato roots colonized by AMF, which has not been previously demonstrated. Furthermore, we observed that a virus-dependent reduction in nutrient exchange could occur in mycorrhizal roots in the presence of PVY. These findings provide an insights into the interplay between virus and AMF.Key messageThe article, based on the results of transcriptomic analysis, identifies the symbiosis-related and defense-related determinants activated in mycorrhizal potatoes infected by potato virus Y (PVY).

Background The major pathogenesis associated with Fasciola hepatica infection results from the extensive tissue damage caused by the tunnelling and feeding activity of immature flukes during their migration, growth and development in the liver. This is compounded by the pathology caused by host innate and adaptive immune responses that struggle to simultaneously counter infection and repair tissue damage. Results Complementary transcriptomic and proteomic approaches defined the F. hepatica factors associated with their migration in the liver, and the resulting immune-pathogenesis. Immature liver-stage flukes express ~ 8000 transcripts that are enriched for transcription and translation processes reflective of intensive protein production and signal transduction pathways. Key pathways that regulate neoblast/pluripotent cells, including the PI3K-Akt signalling pathway, are particularly dominant and emphasise the importance of neoblast-like cells for the parasite’s rapid development. The liver-stage parasites display different secretome profiles, reflecting their distinct niche within the host, and supports the view that cathepsin peptidases, cathepsin peptidase inhibitors, saposins and leucine aminopeptidases play a central role in the parasite’s destructive migration, and digestion of host tissue and blood. Immature flukes are also primed for countering immune attack by secreting immunomodulating fatty acid binding proteins (FABP) and helminth defence molecules (FhHDM). Combined with published host microarray data, our results suggest that considerable immune cell infiltration and subsequent fibrosis of the liver tissue exacerbates oxidative stress within parenchyma that compels the expression of a range of antioxidant molecules within both host and parasite. Conclusions The migration of immature F. hepatica parasites within the liver is associated with an increase in protein production, expression of signalling pathways and neoblast proliferation that drive their rapid growth and development. The secretion of a defined set of molecules, particularly cathepsin L peptidases, peptidase-inhibitors, saponins, immune-regulators and antioxidants allow the parasite to negotiate the liver micro-environment, immune attack and increasing levels of oxidative stress. This data contributes to the growing F. hepatica -omics information that can be exploited to understand parasite development more fully and for the design of novel control strategies to prevent host liver tissue destruction and pathology.

Background Fowl adenovirus serotype 8b (FAdV-8b) is the etiological agent of inclusion body hepatitis’ outbreaks in chicken farms worldwide and a threat to the poultry industry. The isolation and identification of isolates of this pathogen are abundant, yet the pathogenesis and subsequent molecular mechanism are significantly understudied. Hence, this study aims to identify the differential gene expression profile of specific pathogen-free chicken livers infected with FAdV-8b strain UPMT1901 isolate. Results The harvested chicken livers were subjected to biological pooling and transcriptomic profiling via RNA-sequencing, according to the days of post-infections (dpi). A total of 21,662 genes were identified in both control and infected groups, enriched in various biological processes and pathways, displaying patterns of disease progressions. The transcriptome analysis results revealed a three-fold reduced pattern of gene regulation with 9146, 7335, and 3800 significant differential expressed genes (DEGs) at 2-, 5-, and 7-dpi (dpi), respectively. Conclusion These findings elucidate insights on the holistic disease progression of FAdV-8b in liver, from viral incubation and replication at 0–2-dpi, major metabolite hijacking at 3–5-dpi, followed by constant regulation of immune response at 6- and 7-dpi. Based on intensive literature review conducted prior to this study, this study is considered as the first study of the serotype 8b infection pathogenesis at the target organ, providing a better understanding and wide basis of pathogen-host interaction in FAdV-8b in chickens and its progression.

Immunity to cholera is largely mediated by antibodies targeting the O-specific polysaccharide (OSP) of Vibrio cholerae, including through agglutination as well as inhibition of bacterial motility. Here, we used bacterial transcriptomic, biochemical, and cellular analyses to evaluate additional effects of OSP-specific antibodies on V. cholerae in complex media containing mucin and in a human enteroid-derived monolayer colonization model. We found that anti-OSP antibody in mucin impacts bacterial motility, growth, metabolic activity, extracellular matrix production, and levels of cyclic di-GMP. We did not observe a direct effect on bacterial viability, sodium motive force gradient, membrane integrity for large molecules, or virulence gene or regulon expression in bacterial cultures, although cholera toxin detection was significantly decreased in the enteroid model. Our results uncover the broad impact of anti-OSP antibodies in the presence of mucin on V. cholerae physiology and suggest several ways OSP-specific antibodies mediate protection against cholera in humans.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly recombinogenic pathogen that threatens global swine production. Multiple PRRSV lineages co-circulate in China, with lineage 1.8 being the predominant epidemic strain. However, the pathogenic characteristics and differences among strains from distinct lineages remain insufficiently studied. In this study, three novel recombinant PRRSV strains (GX-2428, GX-3264, and GX-5430) were isolated in Guangxi, China. Phylogenetic analysis of the ORF5 gene classified the three strains into lineage 3 (QYYZ-like), lineage 1.8 (NADC30-like), and lineage 1.5 (NADC34-like), respectively. Pathogenicity tests in piglets demonstrated that, compared with the control group, both GX-2428 and GX-3264 induced significant fever, whereas GX-5430 caused only a transient and milder febrile response. Infected piglets exhibited elevated levels of pro-inflammatory (IL-1β and TNF-α) and immunomodulatory cytokines (IL-4 and IL-10) compared to the control group. Postmortem analysis revealed that although viral shedding had ceased, high viral loads persisted in the lungs, tonsils, and lymph nodes of the infected piglets. Transcriptomic analysis of piglet lung tissues revealed that GX-5430 infection predominantly enriched pathways related to cellular transformation, signal transduction, and metabolic reprogramming. However, infections with GX-2428 or GX-3264 were significantly enriched in immune-related pathways, thereby inducing stronger immune activation and inflammatory responses. In conclusion, these findings highlight the recombination characteristics and lineage-specific pathogenic mechanisms of PRRSV, providing novel insights for the development of future prevention and control strategies.

Melanin is an Aspergillus flavus cell wall component that provides chemical and physical protection to the organism. However, the molecular and biological mechanisms modulating melanin-mediated host–pathogen interaction in A. flavus keratitis are not well understood. This work aimed to compare the morphology, surface proteome profile, and virulence of melanized conidia (MC) and non-melanized conidia (NMC) of A. flavus . Kojic acid treatment inhibited melanin synthesis in A. flavus , and the conidial surface protein profile was significantly different in kojic acid-treated non-melanized conidia. Several cell wall-associated proteins and proteins responsible for oxidative stress, carbohydrate, and chitin metabolic pathways were found only in the formic acid extracts of NMC. Scanning electron microscopy (SEM) analysis showed the conidial surface morphology difference between the NMC and MC, indicating the role of melanin in the structural integrity of the conidial cell wall. The levels of calcofluor white staining efficiency were different, but there was no microscopic morphology difference in lactophenol cotton blue staining between MC and NMC. Evaluation of the virulence of MC and NMC in the Galleria mellonella model showed NMC was less virulent compared to MC. Our findings showed that the integrity of the conidial surface is controlled by the melanin layer. The alteration in the surface protein profile indicated that many surface proteins are masked by the melanin layer, and hence, melanin can modulate the host response by preventing the exposure of fungal proteins to the host immune defense system. The G. mellonella virulence assay also confirmed that the NMC were susceptible to host defense as in other Aspergillus pathogens. Key points • l-DOPA melanin production was inhibited in A. flavus isolates by kojic acid, and for the first time, scanning electron microscopy (SEM) analysis revealed morphological differences between MC and NMC of A. flavus strains • Proteome profile of non-melanized conidia showed more conidial surface proteins and these proteins were mainly involved in the virulence, oxidative stress, and metabolism pathways • Non-melanized conidia of A. flavus strains were shown to be less virulent than melanised conidia in an in vivo virulence experiment with the G. melonella model

Despite the plant health-promoting effects of plant microbiota, these assemblages also comprise potentially detrimental microbes. How plant immunity controls its microbiota to promote plant health under these conditions remains largely unknown. We find that commensal bacteria isolated from healthy Arabidopsis plants trigger diverse patterns of reactive oxygen species (ROS) production dependent on the immune receptors and completely on the NADPH oxidase RBOHD that selectively inhibited specific commensals, notably Xanthomonas L148. Through random mutagenesis, we find that L148 gspE , encoding a type II secretion system (T2SS) component, is required for the damaging effects of Xanthomonas L148 on rbohD mutant plants. In planta bacterial transcriptomics reveals that RBOHD suppresses most T2SS gene expression including gspE . L148 colonization protected plants against a bacterial pathogen, when gspE was inhibited by ROS or mutation. Thus, a negative feedback loop between Arabidopsis ROS and the bacterial T2SS tames a potentially detrimental leaf commensal and turns it into a microbe beneficial to the host. The plant immune output reactive oxygen species tames a detrimental bacterial commensal from native microbiota by suppressing a bacterial secretion system, allowing the co-existence and turning it into a beneficial bacterium to the host.