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Virulence Dec 2024O'nyong-nyong virus (ONNV) is a neglected mosquito-borne alphavirus belonging to the family. ONNV is known to be responsible for sporadic outbreaks of acute febrile... (Review)
Review
O'nyong-nyong virus (ONNV) is a neglected mosquito-borne alphavirus belonging to the family. ONNV is known to be responsible for sporadic outbreaks of acute febrile disease and polyarthralgia in Africa. As climate change increases the geographical range of known and potential new vectors, recent data indicate a possibility for ONNV to spread outside of the African continent and grow into a greater public health concern. In this review, we summarise the current knowledge on ONNV epidemiology, host-pathogen interactions, vector-virus responses, and insights into possible avenues to control risk of further epidemics. In this review, the limited ONNV literature is compared and correlated to other findings on mainly Old World alphaviruses. We highlight and discuss studies that investigate viral and host factors that determine viral-vector specificity, along with important mechanisms that determine severity and disease outcome of ONNV infection.
Topics: Humans; Animals; Virulence; Host-Pathogen Interactions; O'nyong-nyong Virus; Alphavirus Infections; Mosquito Vectors; Africa; Pandemics
PubMed: 38797948
DOI: 10.1080/21505594.2024.2355201 -
Microbiology Spectrum May 2024Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the swine industry. Frequent mutations and recombinations account for...
Isolation and pathogenicity comparison of two novel natural recombinant porcine reproductive and respiratory syndrome viruses with different recombination patterns in Southwest China.
Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the swine industry. Frequent mutations and recombinations account for PRRSV immune evasion and the emergence of novel strains. In this study, we isolated and characterized two novel PRRSV-2 strains from Southwest China exhibiting distinct recombination patterns. They were designated SCABTC-202305 and SCABTC-202309. Phylogenetic results indicated that SCABTC-202305 was classified as lineage 8, and SCABTC-202309 was classified as lineage 1.8. Amino acid mutation analysis identified unique amino acid substitutions and deletions in ORF5 and Nsp2 genes. The results of the recombination analysis revealed that SCABTC-202305 is a recombinant with JXA1 as the major parental strain and NADC30 as the minor parental strain. At the same time, SCABTC-202309 is identified as a recombinant with NADC30 as the major parental strain and JXA1 as the minor parental strain. In this study, we infected piglets with SCABTC-202305, SCABTC-202309, or mock inoculum (control) to study the pathogenicity of these isolates. Although both isolated strains were pathogenic, SCABTC-202305-infected piglets exhibited more severe clinical signs and higher mortality, viral load, and antibody response than SCABTC-202309-infected piglets. SCABTC-202305 also caused more extensive lung lesions based on histopathology. Our findings suggest that the divergent pathogenicity observed between the two novel PRRSV isolates may be attributed to variations in the genetic information encoded by specific genomic regions. Elucidating the genetic determinants governing PRRSV virulence and transmissibility will inform efforts to control this devastating swine pathogen.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) is one of the most critical pathogens impacting the global swine industry. Frequent mutations and recombinations have made the control of PRRSV increasingly difficult. Following the NADC30-like PRRSV pandemic, recombination events involving PRRSV strains have further increased. We isolated two novel field PRRSV recombinant strains, SCABTC-202305 and SCABTC-202309, exhibiting different recombination patterns and compared their pathogenicity in animal experiments. The isolates caused higher viral loads, persistent fever, marked weight loss, moderate respiratory clinical signs, and severe histopathologic lung lesions in piglets. Elucidating correlations between recombinant regions and pathogenicity in these isolates can inform epidemiologic tracking of emerging strains and investigations into viral adaptive mechanisms underlying PRRSV immunity evasion. Our findings underscore the importance of continued genomic surveillance to curb this economically damaging pathogen.
Topics: Porcine respiratory and reproductive syndrome virus; Animals; Swine; Porcine Reproductive and Respiratory Syndrome; China; Recombination, Genetic; Phylogeny; Virulence; Mutation; Genome, Viral
PubMed: 38511956
DOI: 10.1128/spectrum.04071-23 -
PLoS Genetics Aug 2023Escherichia coli is both a highly prevalent commensal and a major opportunistic pathogen causing bloodstream infections (BSI). A systematic analysis characterizing the...
Escherichia coli is both a highly prevalent commensal and a major opportunistic pathogen causing bloodstream infections (BSI). A systematic analysis characterizing the genomic determinants of extra-intestinal pathogenic vs. commensal isolates in human populations, which could inform mechanisms of pathogenesis, diagnostic, prevention and treatment is still lacking. We used a collection of 912 BSI and 370 commensal E. coli isolates collected in France over a 17-year period (2000-2017). We compared their pangenomes, genetic backgrounds (phylogroups, STs, O groups), presence of virulence-associated genes (VAGs) and antimicrobial resistance genes, finding significant differences in all comparisons between commensal and BSI isolates. A machine learning linear model trained on all the genetic variants derived from the pangenome and controlling for population structure reveals similar differences in VAGs, discovers new variants associated with pathogenicity (capacity to cause BSI), and accurately classifies BSI vs. commensal strains. Pathogenicity is a highly heritable trait, with up to 69% of the variance explained by bacterial genetic variants. Lastly, complementing our commensal collection with an older collection from 1980, we predict that pathogenicity continuously increased through 1980, 2000, to 2010. Together our findings imply that E. coli exhibit substantial genetic variation contributing to the transition between commensalism and pathogenicity and that this species evolved towards higher pathogenicity.
Topics: Humans; Escherichia coli; Escherichia coli Infections; Genes, Bacterial; Virulence; Sepsis; Phylogeny
PubMed: 37531401
DOI: 10.1371/journal.pgen.1010842 -
Virulence Dec 2024Enterohemorrhagic (EHEC) is an important zoonotic pathogen that is a major cause of foodborne diseases in most developed and developing countries and can cause... (Review)
Review
Enterohemorrhagic (EHEC) is an important zoonotic pathogen that is a major cause of foodborne diseases in most developed and developing countries and can cause uncomplicated diarrhoea, haemorrhagic colitis, and haemolytic uraemic syndrome. O islands (OIs), which are unique genomic islands in EHEC O157:H7, are composed of 177 isolated genomic features and harbour 26% of the total genes that are absent in the non-pathogenic K-12 genome. In the last twenty years, many OI-encoded proteins have been characterized, including proteins regulating virulence, motility, and acid resistance. Given the critical role of regulatory proteins in the systematic and hierarchical regulation of bacterial biological processes, this review summarizes the OI-encoded regulatory proteins in EHEC O157:H7 characterized to date, emphasizing OI-encoded regulatory proteins for bacterial virulence, motility, and acid resistance. This summary will be significant for further exploration and understanding of the virulence and pathogenesis of EHEC O157:H7.
Topics: Humans; Genomic Islands; Escherichia coli O157; Transcription Factors; Enterohemorrhagic Escherichia coli; Virulence; Escherichia coli Infections; Escherichia coli Proteins
PubMed: 38357901
DOI: 10.1080/21505594.2024.2313407 -
PLoS Neglected Tropical Diseases Jan 2024Dengue is a mosquito-borne disease that has spread to over 100 countries. Its symptoms vary from the relatively mild acute febrile illness called dengue fever to the...
Dengue is a mosquito-borne disease that has spread to over 100 countries. Its symptoms vary from the relatively mild acute febrile illness called dengue fever to the much more severe dengue shock syndrome. Dengue is caused by dengue virus (DENV), which belongs to the Flavivirus genus of the family Flaviviridae. There are four serotypes of DENV, i.e., DENV1 to DENV4, and each serotype is divided into distinct genotypes. Thailand is an endemic area where all four serotypes of DENV co-circulate. Genome sequencing of the DENV2 that was isolated in Thailand in 2016 and 2017 revealed the emergence of the Cosmopolitan genotype and its co-circulation with the Asian-I genotype. However, it was unclear whether different genotypes have different levels of viral replication and pathogenicity. Focus-forming assay (FFA) results showed that clinical isolates of these genotypes differed in focus size and proliferative capacity. Using circular polymerase extension reaction, we generated parental and chimeric viruses with swapped genes between these two DENV2 genotypes, and compared their focus sizes and infectivity titers using FFA. The results showed that the focus size was larger when the structural proteins and/or non-structural NS1-NS2B proteins were derived from the Cosmopolitan virus. The infectious titers were consistent with the focus sizes. Single-round infectious particle assay results confirmed that chimeric viruses with Cosmopolitan type structural proteins, particularly prM/E, had significantly increased luciferase activity. Replicon assay results showed that Cosmopolitan NS1-NS2B proteins had increased reporter gene expression levels. Furthermore, in interferon-receptor knock-out mice, viruses with Cosmopolitan structural and NS1-NS2B proteins had higher titers in the blood, and caused critical disease courses. These results suggested that differences in the sequences within the structural and NS1-NS2B proteins may be responsible for the differences in replication, pathogenicity, and infectivity between the Asian-I and Cosmopolitan viruses.
Topics: Animals; Mice; Dengue Virus; Dengue; Virulence; Serogroup; Genotype; Virus Replication
PubMed: 38190404
DOI: 10.1371/journal.pntd.0011885 -
Disease Models & Mechanisms Oct 2023Invasive fungal infections represent a significant global health problem, and present several clinical challenges, including limited treatment options, increasing rates... (Review)
Review
Invasive fungal infections represent a significant global health problem, and present several clinical challenges, including limited treatment options, increasing rates of antifungal drug resistance and compounding comorbidities in affected patients. Metals, such as copper, iron and zinc, are critical for various biological and cellular processes across phyla. In mammals, these metals are important determinants of immune responses, but pathogenic microbes, including fungi, also require access to these metals to fuel their own growth and drive expression of major virulence traits. Therefore, host immune cells have developed strategies to either restrict access to metals to induce starvation of invading pathogens or deploy toxic concentrations within phagosomes to cause metal poisoning. In this Review, we describe the mechanisms regulating fungal scavenging and detoxification of copper, iron and zinc and the importance of these mechanisms for virulence and infection. We also outline how these metals are involved in host immune responses and the consequences of metal deficiencies or overloads on how the host controls invasive fungal infections.
Topics: Animals; Humans; Copper; Virulence; Metals; Iron; Zinc; Invasive Fungal Infections; Mammals
PubMed: 37905492
DOI: 10.1242/dmm.050393 -
Virology Journal Aug 2023Porcine circovirus type 2 (PCV2), a member of the genus Circovirus and family Circoviridae, is a closed, small, circular, and single-stranded DNA virus, and it is a...
BACKGROUND
Porcine circovirus type 2 (PCV2), a member of the genus Circovirus and family Circoviridae, is a closed, small, circular, and single-stranded DNA virus, and it is a crucial swine pathogen of porcine circovirus-associated diseases (PCVADs). PCV2 was first detected in PK-15(ATCC-CCL) cells in 1974, which has caused significant economic loss to the swine industry throughout the world. And the first case of PCV2 was reported in China in 2000. At present, PCV2d is the main genotype circulating widely in China.
METHODS
Lymph samples were obtained from piglets with emaciation and respiratory disease in Guangxi province, China. The main pathogens were detected via PCR from lymph samples, and then PCV2-single positive samples were used to inoculate with PK-15 cells. After successive generations, the isolate was subsequently identified by polymerase chain reaction (PCR), immunofluorescence assay (IFA), Western blot (WB), and transmission electron microscopic (TEM). The full-length genome and genetic characterization of isolates were analyzed by Sanger sequencing. The TCID of the PCV2-GX-6 was determined by IFA, and the pathogenicity of PCV2 in BALB/c mice was analyzed via the mouse model.
RESULTS
The isolates were successfully isolated from clinical samples. The complete genome of PCV2-GX-4, PCV2-GX-6, PCV2-GX-7, PCV2-GX-11 and PCV2-GX-16 have been amplified, sequenced, and deposited in GenBank (accession no.: OR133747, OQ803314, OR133748, OR133749, OR133750). Homology and phylogenetic analysis with reference strains showed that the isolates belonged to the PCV2d genotype. The PCV2-GX-6 could be stably passaged more than 30 times in PK-15 cells. PCV2-GX-6 was identified by PCR, IFA, WB and TEM. The results of homology showed that PCV2-GX-6 was closely related to the reference strains PCV2-JS17-8 (GenBank accession no.: MH211363). Pathogenicity studies in mice have shown that PCV2-GX-6 can lead to growth inhibition of mice. Meanwhile PCV2-GX-6 caused the typical lesions of spleen, lung and kidney. The results of qPCR showed that PCV2 can effectively proliferate in the liver, spleen, lung, and kidney.
CONCLUSION
PCV2-GX-6 can successfully infect BLAB/c mice, effectively proliferate in major organs, and possessed high pathogenicity. In conclusion, combined with the genotype and pathogenicity of PCV2d currently prevalent, PCV2-GX-6 can be used as a candidate vaccine strain.
Topics: Animals; Mice; Swine; Circovirus; China; Phylogeny; Virulence; Mice, Inbred BALB C
PubMed: 37644571
DOI: 10.1186/s12985-023-02161-5 -
Virulence Dec 2024The pervasive presence of and other coagulase-negative staphylococci on the skin and mucous membranes has long underpinned a casual disregard for the infection risk... (Review)
Review
The pervasive presence of and other coagulase-negative staphylococci on the skin and mucous membranes has long underpinned a casual disregard for the infection risk that these organisms pose to vulnerable patients in healthcare settings. Prior to the recognition of biofilm as an important virulence determinant in , isolation of this microorganism in diagnostic specimens was often overlooked as clinically insignificant with potential delays in diagnosis and onset of appropriate treatment, contributing to the establishment of chronic infection and increased morbidity or mortality. While impressive progress has been made in our understanding of biofilm mechanisms in this important opportunistic pathogen, research into other virulence determinants has lagged . In this review, the broader virulence potential of including biofilm, toxins, proteases, immune evasion strategies and antibiotic resistance mechanisms is surveyed, together with current and future approaches for improved therapeutic interventions.
Topics: Staphylococcus epidermidis; Humans; Staphylococcal Infections; Virulence; Biofilms; Virulence Factors; Animals; Opportunistic Infections; Immune Evasion; Anti-Bacterial Agents
PubMed: 38868991
DOI: 10.1080/21505594.2024.2359483 -
International Journal of Molecular... Aug 2023Intestinal diseases caused by protistan parasites of the genera (giardiasis), (amoebiasis), (cryptosporidiosis) and (blastocystosis) represent a major burden in... (Review)
Review
Intestinal diseases caused by protistan parasites of the genera (giardiasis), (amoebiasis), (cryptosporidiosis) and (blastocystosis) represent a major burden in human and animal populations worldwide due to the severity of diarrhea and/or inflammation in susceptible hosts. These pathogens interact with epithelial cells, promoting increased paracellular permeability and enterocyte cell death (mainly apoptosis), which precede physiological and immunological disorders. Some cell-surface-anchored and molecules secreted from these parasites function as virulence markers, of which peptide hydrolases, particularly cysteine proteases (CPs), are abundant and have versatile lytic activities. Upon secretion, CPs can affect host tissues and immune responses beyond the site of parasite colonization, thereby increasing the pathogens' virulence. The four intestinal protists considered here are known to secrete predominantly clan A (C1- and C2-type) CPs, some of which have been characterized. CPs of (e.g., Giardipain-1) and (EhCPs 1-6 and EhCP112) degrade mucin and villin, cause damage to intercellular junction proteins, induce apoptosis in epithelial cells and degrade immunoglobulins, cytokines and defensins. In , five Cryptopains are encoded in its genome, but only Cryptopains 4 and 5 are likely secreted. In sp., a legumain-activated CP, called Blastopain-1, and legumain itself have been detected in the extracellular medium, and the former has similar adverse effects on epithelial integrity and enterocyte survival. Due to their different functions, these enzymes could represent novel drug targets. Indeed, some promising results with CP inhibitors, such as vinyl sulfones (K11777 and WRR605), the garlic derivative, allicin, and purified amoebic CPs have been obtained in experimental models, suggesting that these enzymes might be useful drug targets.
Topics: Animals; Humans; Virulence; Virulence Factors; Cysteine Proteases; Cryptosporidiosis; Cryptosporidium
PubMed: 37629029
DOI: 10.3390/ijms241612850 -
Nature Communications Aug 2023Extracellular vesicles (EVs) are important for cell-to-cell communication in animals. EVs also play important roles in plant-microbe interactions, but the underlying...
Extracellular vesicles (EVs) are important for cell-to-cell communication in animals. EVs also play important roles in plant-microbe interactions, but the underlying mechanisms remain elusive. Here, proteomic analyses of EVs from the soybean (Glycine max) root rot pathogen Phytophthora sojae identify the tetraspanin family proteins PsTET1 and PsTET3, which are recognized by Nicotiana benthamiana to trigger plant immune responses. Both proteins are required for the full virulence of P. sojae. The large extracellular loop (EC2) of PsTET3 is the key region recognized by N. benthamiana and soybean cells in a plant receptor-like kinase NbSERK3a/b dependent manner. TET proteins from oomycete and fungal plant pathogens are recognized by N. benthamiana thus inducing immune responses, whereas plant-derived TET proteins are not due to the sequence divergence of sixteen amino acids at the C-terminal of EC2. This feature allows plants to distinguish self and non-self EVs to trigger active defense responses against pathogenic eukaryotes.
Topics: Proteomics; Phytophthora; Plant Proteins; Virulence; Extracellular Vesicles; Glycine max; Plant Diseases
PubMed: 37573360
DOI: 10.1038/s41467-023-40623-0