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Nature Communications May 2024Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are...
Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat. We show that inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide can cause enhanced respiratory disease during heterologous infection, while use of an alternative adjuvant does not drive disease and promotes heterologous viral clearance. In this work, we highlight the impact of adjuvant selection on inactivated vaccine safety and efficacy against heterologous coronavirus infection.
Topics: Animals; COVID-19 Vaccines; Female; COVID-19; Mice; Vaccines, Inactivated; SARS-CoV-2; Aluminum Hydroxide; Disease Models, Animal; Adjuvants, Immunologic; Adjuvants, Vaccine; Antibodies, Viral; Mice, Inbred BALB C; Humans; Severe acute respiratory syndrome-related coronavirus
PubMed: 38702297
DOI: 10.1038/s41467-024-47450-x -
Experimental and Clinical... Mar 2024Modern immunosuppressive regimens have reduced rejection episodes in renal allograft recipients but have increased the risk of opportunistic infections. Infections are... (Observational Study)
Observational Study
OBJECTIVES
Modern immunosuppressive regimens have reduced rejection episodes in renal allograft recipients but have increased the risk of opportunistic infections. Infections are considered to be the second leading cause of death after cardiovascular complications in renal allograft recipients. Data on opportunistic infections affecting the allograft itself are scarce. The present study describes the spectrum of renal opportunistic infections and their outcomes diagnosed on renal allograft biopsies and nephrectomy specimens.
MATERIALS AND METHODS
Our retrospective observational study was conducted from December 2011 to December 2021. We analyzed infectious episodes diagnosed on renal allograft biopsies or graft nephrectomy specimens. We obtained clinical, epidemiological, and laboratory details for analyses from hospital records.
RESULTS
BK virus nephropathy was the most common opportunistic infection affecting the allograft, accounting for 47% of cases, followed by bacterial graft pyelonephritis (25%). Mucormycosis was the most common fungal infection. The diagnosis of infection from day of transplant ranged from 14 days to 39 months. Follow-up periods ranged from 1 to 10 years. Mortality was highest among patients with opportunistic fungal infection (62%), followed by viral infections, and graft failure rate was highest in patients with graft pyelonephritis (50%). Among patients with BK polyomavirus nephropathy, 45% had stable graft function compared with just 33% of patients with bacterial graft pyelonephritis.
CONCLUSIONS
BK polyoma virus infection was the most common infection affecting the renal allograft in our study. Although fungal infections caused the highest mortality among our patients, bacterial graft pyelonephritis was responsible for maximum graft failure. Correctly identifying infections on histology is important so that graft and patient life can be prolonged.
Topics: Humans; Kidney Transplantation; Retrospective Studies; Male; Female; Nephrectomy; Middle Aged; Adult; Biopsy; Treatment Outcome; Time Factors; Risk Factors; Opportunistic Infections; Allografts; Living Donors; Graft Survival; Turkey; Aged; Pyelonephritis; Polyomavirus Infections
PubMed: 38695589
DOI: 10.6002/ect.2023.0200 -
Experimental and Clinical... Mar 2024Before the advent of direct-acting antiviral therapy for hepatitis C virus, a large proportion of kidneys from donors with hepatitis C viremia were discarded. Hepatitis... (Observational Study)
Observational Study
OBJECTIVES
Before the advent of direct-acting antiviral therapy for hepatitis C virus, a large proportion of kidneys from donors with hepatitis C viremia were discarded. Hepatitis C virus is now amenable to effective treatment with excellent seronegativity rates. In this study, we review the outcomes of hepatitis C viremic kidneys transplanted into hepatitis C-naive recipients.
MATERIALS AND METHODS
In this retrospective observational study, we examined 6 deceased donor kidneys with hepatitis C viremia that were transplanted into hepatitis C-naive recipients between March 2020 and April 2021 at a single center. Because of health insurance constraints, patients were treated for hepatitis C virus with glecaprevir/pibrentasvir for 8 weeks following seroconversion posttransplant. Primary outcome measured was viral seroconversion; secondary outcomes included graft function, posttransplant complications, and all-cause mortality.
RESULTS
On average, patients seroconverted 6 days (range, 4-10 d) after transplant and began treatment 26 days (range, 15-37 d) after seroconversion. An 8-week course of antiviral treatment was successful in preventing acute hepatitis C virus infection in all patients. Posttransplant median creatinine was 1.96 mg/dL (range, 1-4.55 mg/dL), whereas median estimated glomerular filtration rate was 41.33 mL/min/1.73 m2 (range, 17-85 mL/min/1.73 m2). Patient survival rate was 66.7%, and death-censored graft survival rate was 100%. Two patients died from unrelated reasons: 1 from acute respiratory failure secondary to SARS-CoV-2 infection and 1 from posttransplant lymphoproliferative disorder. Two patients developed allograft rejection posttransplant (1 developed antibody mediated rejection, 1 developed borderline T-cell-mediated cellular rejection). Other major complications included neutropenia, fungal rash, SARS-CoV-2 infection, cytomegalovirus, BK virus, and Epstein-Barr virus reactivation.
CONCLUSIONS
Use of hepatitis C-viremic donor kidneys for transplant is a safe option and has great potential to increase the kidney donor pool, as long as high index of suspicion is maintained for allograft rejection and opportunistic infections.
Topics: Humans; Kidney Transplantation; Retrospective Studies; Male; Female; Middle Aged; Antiviral Agents; Hepatitis C; Treatment Outcome; Viremia; Adult; Time Factors; Donor Selection; Risk Factors; Tissue Donors; Drug Combinations; Graft Survival; Aged; Rural Health Services; Seroconversion; Benzimidazoles; Pyrrolidines; Quinoxalines
PubMed: 38695587
DOI: 10.6002/ect.2024.0034 -
Viruses Apr 2024Southern Africa Territories 2 (SAT2) foot-and-mouth disease (FMD) has crossed long-standing regional boundaries in recent years and entered the Middle East. However, the...
Chimeric Porcine Parvovirus VP2 Virus-like Particles with Epitopes of South African Serotype 2 Foot-and-Mouth Disease Virus Elicits Specific Humoral and Cellular Responses in Mice.
Southern Africa Territories 2 (SAT2) foot-and-mouth disease (FMD) has crossed long-standing regional boundaries in recent years and entered the Middle East. However, the existing vaccines offer poor cross-protection against the circulating strains in the field. Therefore, there is an urgent need for an alternative design approach for vaccines in anticipation of a pandemic of SAT2 Foot-and-mouth disease virus (FMDV). The porcine parvovirus (PPV) VP2 protein can embed exogenous epitopes into the four loops on its surface, assemble into virus-like particles (VLPs), and induce antibodies and cytokines to PPV and the exogenous epitope. In this study, chimeric porcine parvovirus VP2 VLPs (chimeric PPV-SAT2-VLPs) expressing the T-and/or B-cell epitopes of the structural protein VP1 of FMDV SAT2 were produced using the recombinant pFastBac™ Dual vector of baculoviruses in Sf9 and HF cells We used the Bac-to-Bac system to construct the recombinant baculoviruses. The VP2-VLP--SAT2 chimeras displayed chimeric T-cell epitope (amino acids 21-40 of VP1) and/or the B-cell epitope (amino acids 135-174) of SAT FMDV VP1 by substitution of the corresponding regions at the N terminus (amino acids 2-23) and/or loop 2 and/or loop 4 of the PPV VP2 protein, respectively. In mice, the chimeric PPV-SAT2-VLPs induced specific antibodies against PPV and the VP1 protein of SAT2 FMDV. The VP2-VLP-SAT2 chimeras induced specific antibodies to PPV and the VP1 protein specific epitopes of FMDV SAT2. In this study, as a proof-of-concept, successfully generated chimeric PPV-VP2 VLPs expressing epitopes of the structural protein VP1 of FMDV SAT2 that has a potential to prevent FMDV SAT2 and PPV infection in pigs.
Topics: Animals; Foot-and-Mouth Disease Virus; Mice; Foot-and-Mouth Disease; Capsid Proteins; Parvovirus, Porcine; Antibodies, Viral; Viral Vaccines; Vaccines, Virus-Like Particle; Swine; Immunity, Humoral; Immunity, Cellular; Epitopes, T-Lymphocyte; Epitopes, B-Lymphocyte; Serogroup; Mice, Inbred BALB C; Female; Epitopes; Sf9 Cells; Antibodies, Neutralizing; Antigens, Viral
PubMed: 38675963
DOI: 10.3390/v16040621 -
International Journal of Molecular... Apr 2024Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to raise concerns worldwide. Numerous host factors involved in SARS-CoV-2 infection have...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to raise concerns worldwide. Numerous host factors involved in SARS-CoV-2 infection have been identified, but the regulatory mechanisms of these host factor remain unclear. Here, we report the role of G-quadruplexes (G4s) located in the host factor promoter region in SARS-CoV-2 infection. Using bioinformatics, biochemical, and biological assays, we provide evidence for the presence of G4 structures in the promoter regions of SARS-CoV-2 host factors NRP1. Specifically, we focus on two representative G4s in the promoter and highlight its importance in SARS-CoV-2 pathogenesis. The presence of the G4 structure greatly increases NRP1 expression, facilitating SARS-CoV-2 entry into cells. Utilizing published single-cell RNA sequencing data obtained from simulated SARS-CoV-2 infection in human bronchial epithelial cells (HBECs), we found that ciliated cells with high levels of are prominently targeted by the virus during infection. Furthermore, our study identifies E2F1 act as a transcription factor that binds to G4s. These findings uncover a previously unknown mechanism underlying SARS-CoV-2 infection and suggest that targeting G4 structures could be a potential strategy for COVID-19 prevention and treatment.
Topics: Humans; COVID-19; E2F1 Transcription Factor; Epithelial Cells; G-Quadruplexes; Neuropilin-1; Promoter Regions, Genetic; SARS-CoV-2; Virus Internalization
PubMed: 38674009
DOI: 10.3390/ijms25084422 -
International Journal of Molecular... Apr 2024Anthocyanins are ubiquitous pigments derived from the phenylpropanoid compound conferring red, purple and blue pigmentations to various organs of horticultural crops....
Anthocyanins are ubiquitous pigments derived from the phenylpropanoid compound conferring red, purple and blue pigmentations to various organs of horticultural crops. The metabolism of flavonoids in the cytoplasm leads to the biosynthesis of anthocyanin, which is then conveyed to the vacuoles for storage by plant (). Although is important for transporting anthocyanin in plants, its identification and characterization in eggplant ( L.) remains obscure. In this study, a total of 40 genes were obtained in the eggplant genome and classified into seven distinct chief groups based on the evolutionary relationship with GST genes. The seven subgroups of eggplant GST genes () comprise: dehydroascorbate reductase (DHAR), elongation factor 1Bγ (EF1Bγ), Zeta (Z), Theta(T), Phi(F), Tau(U) and tetra-chlorohydroquinone dehalogenase TCHQD. The 40 genes were unevenly distributed throughout the 10 eggplant chromosomes and were predominantly located in the cytoplasm. Structural gene analysis showed similarity in exons and introns within a subgroup. Six pairs of both tandem and segmental duplications have been identified, making them the primary factors contributing to the evolution of the . Light-related cis-regulatory elements were dominant, followed by stress-related and hormone-responsive elements. The syntenic analysis of orthologous genes indicated that eggplant, Arabidopsis and tomato ( L.) counterpart genes seemed to be derived from a common ancestry. RNA-seq data analyses showed high expression of 13 SmGST genes with being glaringly upregulated on the peel of purple eggplant but showed no or low expression on eggplant varieties with green or white peel. Subsequently, had a strong positive correlation with anthocyanin content and with anthocyanin structural genes like ( = 0.9), ( = 0.85), ( = 0.82) and ( = 0.7). The suppression of through virus-induced gene silencing (VIGs) resulted in a decrease in anthocyanin on the infiltrated fruit surface. In a nutshell, results from this study established that has the potential of anthocyanin accumulation in eggplant peel and offers viable candidate genes for the improvement of purple eggplant. The comprehensive studies of the family genes provide the foundation for deciphering molecular investigations into the functional analysis of genes in eggplant.
Topics: Anthocyanins; Arabidopsis; Chromosomes, Plant; Fruit; Gene Expression Regulation, Plant; Genome, Plant; Glutathione Transferase; Phylogeny; Plant Proteins; Solanum melongena
PubMed: 38673847
DOI: 10.3390/ijms25084260 -
Journal of Clinical Medicine Apr 2024The John Cunningham virus (JCV) is a polyomavirus that usually infects people at a young age and does not cause any symptoms in immunocompetent individuals. However, in... (Review)
Review
The John Cunningham virus (JCV) is a polyomavirus that usually infects people at a young age and does not cause any symptoms in immunocompetent individuals. However, in immunocompromised individuals, such as kidney transplant recipients, JCV can cause severe and potentially fatal disease. Unfortunately, JCV has not been researched as extensively as the BK virus and is not mentioned in relevant kidney transplant guidelines. This lack of attention to JCV can lead to less consideration in kidney transplant patients' care. Surveillance using locally available diagnostic methods is of the utmost importance. The presence of JCV can be diagnosed with urine decoy cells, viruria, or viremia verified by the PCR method. A low threshold for considering JCV as a possible cause of any neurological or renal dysfunction in kidney transplant recipients must be maintained. In such cases, kidney and brain biopsy are indicated. Maintaining the appropriate immunosuppression while avoiding over-immunosuppression to prevent JCV disease is crucial, and the approach should be individual, according to overall immunological risk. We hypothesize that the presence of the JCV can indicate overt immunosuppression and identify kidney transplant recipients more prone to opportunistic infections and diseases, including some malignancies. To explore that, future observational studies are needed.
PubMed: 38673491
DOI: 10.3390/jcm13082217 -
Pathogens (Basel, Switzerland) Apr 2024In the absence of an effective antiviral treatment for BK polyomavirus (BKPyV), a better understanding of the epidemiology and time course of BKPyV replication after...
BACKGROUND/OBJECTIVES
In the absence of an effective antiviral treatment for BK polyomavirus (BKPyV), a better understanding of the epidemiology and time course of BKPyV replication after kidney transplantation is needed to limit the virus's impact on the graft outcome.
METHODS
In a 7-year study, we screened more than 430 kidney transplant recipients and analyzed the time course and virological characteristics of BKPyV replication.
RESULTS
Urinary viral replication was observed in 116 (27%) of the 430 patients, and 90 of the 116 (78%) had viral DNAemia. Thirty-eight patients (8.8%) were presumed to have nephropathy (DNAemia > 4 log10 copies/mL). Of the patients with BKPyV replication, 48%, 60%, 71%, and 80% were first found to be positive one, two, three, and four months post-transplantation. The initial viral load in the urine was below 7 log10 copies/mL in 100% of the patients with viral replication first detected before the first month, and this proportion was 57% when viral replication was first detected after the first month. When the BKPyV replication was first detected in a urine sample at month 3 or later, 81.5% of patients had concomitant BKPyV DNAemia. The predominant viral subtype was Ib2 (60%), and there was no apparent relationship between the subtype and the time course of BKPyV replication.
CONCLUSIONS
Urinary BKPyV replication occurs early after renal transplantation and in most patients will increase to a level requiring therapeutic intervention. Close monitoring for BKPyV in the early post-transplantation period would enable the pre-emptive adjustment of the immunosuppression regimen.
PubMed: 38668270
DOI: 10.3390/pathogens13040315 -
Health Science Reports Apr 2024Gastric cancer is a significant global issue with a high death rate. This malignancy could be associated with several viral agents such as EBV, CMV, HHV-6, JCV, and BKV.
Investigation of Epstein-Barr virus, Cytomegalovirus, Human herpesvirus 6, and Polyoma viruses (JC virus, BK virus) among Gastric cancer patients: A cross sectional study.
BACKGROUND AND AIMS
Gastric cancer is a significant global issue with a high death rate. This malignancy could be associated with several viral agents such as EBV, CMV, HHV-6, JCV, and BKV.
OBJECTIVE
Evaluation of EBV, CMV, HHV-6 ,and JCV, BKV frequency among gastric cancer patients.
METHODS
In this cross-sectional study, a total number of 60 gastric cancer specimens (32 male, 28 female) were retrieved from the pathology lab. Formalin-fixed paraffin-embedded tissue was used for molecular testing. DNA was extracted from samples, according to protocol, and used for PCR reaction. Polymerase chain reactions were used to assess CMV, EBV, HHV-6, JCV, and BKV frequency.
RESULTS AND CONCLUSION
The mean age of the participants was 61 years and 53.3% (32) of the participants were Male. A total number of 5 samples (8.34%) were infected with viral agents. Four male gastric samples were infected with EBV (6.67%) and only one female sample contained the BKV genome (1.67%). Totally 8.34% of the samples were infected with EBV and BKV. The CMV, HHV-6, and JCV genome was not detected in the samples. In conclusion, the presence of two viral agents including EBV and BKV among male and female samples respectively, and the genome of other viruses were not detected.
PubMed: 38650724
DOI: 10.1002/hsr2.2043 -
Proceedings of the National Academy of... Apr 2024Organic carbon availability in soil is crucial for shaping microbial communities, yet, uncertainties persist concerning microbial adaptations to carbon levels and the...
Organic carbon availability in soil is crucial for shaping microbial communities, yet, uncertainties persist concerning microbial adaptations to carbon levels and the ensuing ecological and evolutionary consequences. We investigated organic carbon metabolism, antibiotic resistance, and virus-host interactions in soils subjected to 40 y of chemical and organic fertilization that led to contrasting carbon availability: carbon-poor and carbon-rich soils, respectively. Carbon-poor soils drove the enrichment of putative genes involved in organic matter decomposition and exhibited specialization in utilizing complex organic compounds, reflecting scramble competition. This specialization confers a competitive advantage of microbial communities in carbon-poor soils but reduces their buffering capacity in terms of organic carbon metabolisms, making them more vulnerable to environmental fluctuations. Additionally, in carbon-poor soils, viral auxiliary metabolic genes linked to organic carbon metabolism increased host competitiveness and environmental adaptability through a strategy akin to "piggyback the winner." Furthermore, putative antibiotic resistance genes, particularly in low-abundance drug categories, were enriched in carbon-poor soils as an evolutionary consequence of chemical warfare (i.e., interference competition). This raises concerns about the potential dissemination of antibiotic resistance from conventional agriculture that relies on chemical-only fertilization. Consequently, carbon starvation resulting from long-term chemical-only fertilization increases microbial adaptations to competition, underscoring the importance of implementing sustainable agricultural practices to mitigate the emergence and spread of antimicrobial resistance and to increase soil carbon storage.
Topics: Soil; Carbon; Agriculture; Anti-Bacterial Agents; Drug Resistance, Bacterial; Soil Microbiology
PubMed: 38598339
DOI: 10.1073/pnas.2318160121