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Advanced Healthcare Materials Jun 2024The Coronavirus Disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has a significant impact on global health and the economy. It has underscored the urgent need for a...
The Coronavirus Disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has a significant impact on global health and the economy. It has underscored the urgent need for a stable, easily produced and effective vaccine. This study presents a novel approach using SARS-CoV-2 spike (S) protein-conjugated nanoparticles (NPs) in combination with cyclic GMP-AMP (cGAMP) (S-NPs-cGAMP) as a subunit vaccine. When mice are immunized, the antiserum of S-NPs-cGAMP group exhibits a 16-fold increase in neutralizing activity against a pseudovirus, compared to S protein group. Additionally, S-NPs-cGAMP induces even higher levels of neutralizing antibodies. Remarkably, the vaccine also triggers a robust humoral immune response, as evidenced by a notable elevation in virus-specific IgG and IgM antibodies. Furthermore, after 42 days of immunization, there is an observed increase in specific immune cell populations in the spleen. CD3CD4 and CD3CD8T lymphocytes, as well as B220CD19 and CD3CD49b NK lymphocytes, show an upward trend, indicating a positive cellular immune response. Moreover, the S-NPs-cGAMP demonstrates promising results against the Delta strain and exhibits good cross-neutralization potential against other variants. These findings suggest that pDMDAAC NPs is potential adjuvant and could serve as a versatile platform for future vaccine development.
Topics: Animals; Nanoparticles; COVID-19 Vaccines; Mice; SARS-CoV-2; Vaccines, Subunit; Spike Glycoprotein, Coronavirus; COVID-19; Female; Antibodies, Neutralizing; Mice, Inbred BALB C; Antibodies, Viral; Adjuvants, Immunologic; Humans; Immunity, Humoral; Adjuvants, Vaccine; Quaternary Ammonium Compounds; Polymers
PubMed: 38436662
DOI: 10.1002/adhm.202304575 -
Microbiology and Immunology May 2024BK polyomavirus (BKPyV) was the first human polyomavirus to be isolated from an immunosuppressed kidney transplant recipient in 1971. BKPyV reactivation causes...
BK polyomavirus (BKPyV) was the first human polyomavirus to be isolated from an immunosuppressed kidney transplant recipient in 1971. BKPyV reactivation causes BKPyV-associated nephropathy and hemorrhagic cystitis. However, the mechanisms underlying BKPyV replication remain unclear. In the present study, we performed the long-term cultivation of COS-7 cells transfected with archetype KOM-5 DNA, which were designated as COS-BK cells. BKPyV derived from COS-BK cells was characterized by analyzing the amount of the virus based on hemagglutination, viral replication, and the production of viral protein 1 (VP1). Immunostaining showed that VP1-positive cells accounted for a small percentage of COS-BK cells. The nucleotide sequences encompassing the origin of the DNA replication of BKPyV derived from COS-BK cells were generated from KOM-5 by the deletion of an 8-bp sequence, which did not involve T antigen binding sites. BKPyV replicated most efficiently in COS-BK cells in DMEM containing 2% fetal bovine serum. These results indicate that COS-BK cells are a suitable culture system for studying the persistent infection of archetype BKPyV.
Topics: BK Virus; Animals; Chlorocebus aethiops; Virus Replication; COS Cells; Polyomavirus Infections; Humans; Capsid Proteins; DNA, Viral; Persistent Infection; Antigens, Viral, Tumor; Tumor Virus Infections
PubMed: 38433377
DOI: 10.1111/1348-0421.13124 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Oct 2023Currently, patients with pre-exsiting donor-specific antibody (DSA) are prone to antibody-mediated rejection (AMR) after surgery and are at a relatively high risk of...
OBJECTIVES
Currently, patients with pre-exsiting donor-specific antibody (DSA) are prone to antibody-mediated rejection (AMR) after surgery and are at a relatively high risk of postoperative complications and graft failure. The risk of postoperative complications and graft failure is relatively high. This study aims to discuss the clinical outcome of DSA-positive kidney transplantation and analyze the role and safety of preoperative pretreatment in DSA-positive kidney transplantation, providing single-center treatment experience for DSA-positive kidney transplantation.
METHODS
We retrospectively analyzed the clinical data of 15 DSA-positive kidney transplants in the Department of Renal Transplantation of First Affiliated Hospital of Zhengzhou University from August 2017 to July 2022. Eight cases were organ donation after citizen's death (DCD) kidney transplant recipients, of which 3 cases in the early stage were not treated with preoperative desensitisation therapy (DCD untreated group, =3), and 5 recipients were treated with preoperative rituximab desensitisation (DCD preprocessing group, =5). The remaining 7 cases were living related donors recipients (LRD) who received preoperative desensitisation treatment with rituximab and plasma exchange (LRD preprocessing group, =7). We observed and recorded the incidence of complications with changes in renal function and DSA levels in the recipients and the survival of the recipients and transplanted kidneys at 1, 3 and 5 years, and to compare the differences in recovery and postoperative complications between 3 groups.
RESULTS
All 15 recipients were positive for preoperative panel reactive antibody (PRA) and DSA and were treated with methylprednisolone+rabbit anti-human thymocyte immunoglobulin induction before kidney transplantation. DCD untreated group all suffered from DSA level rebound, delayed renal graft function (DGF) and rejection reaction after surgery. After the combined treatment, DSA level was reduced and the graft renal function returned to normal. The DCD preprocessing group were all without antibody rebound, 1 recipient developed DGF and the renal function returned to normal after plasmapheresis, and the remaining 4 recipients recovered their renal function to normal within 2 weeks after the operation. In the LRD preprocessing group, 2 cases had antibody rebound and 1 case had rejection, but all of them recovered to normal after treatment, and DSA was maintained at a low level or even disappeared. The incidence of DGF and rejection in the DCD untreated group were significantly higher than that in the DCD preprocessing group and the LRD preprocessing group; and there were no significant difference in the incidence of postoperative haematuria, proteinuria, bacterial and fungal infections, and BK virus infection between the 3 groups (all >0.05). A total of 11 of the 15 recipients were followed up for more than 1 year, 6 for more than 3 years, and 1 for more than 5 years, and the survival rates of both the recipients and the transplanted kidneys were 100%.
CONCLUSIONS
Effective preoperative pretreatment with desensitization therapy can effectively prevent antibody rebound in DSA-positive kidney transplantation and reduce perioperative complications.
Topics: Animals; Rabbits; Humans; Kidney Transplantation; Retrospective Studies; Rituximab; Tissue Donors; Antibodies; Postoperative Complications
PubMed: 38432887
DOI: 10.11817/j.issn.1672-7347.2023.230144 -
Journal of Water and Health Feb 2024The objective of this study was to assess the occurrence and seasonal frequency of human adenovirus (HAdV), human polyomavirus (HPyV), and human papillomavirus (HPV) in...
The objective of this study was to assess the occurrence and seasonal frequency of human adenovirus (HAdV), human polyomavirus (HPyV), and human papillomavirus (HPV) in urban sewage. The detection of these viruses was carried out by polymerase chain reaction (PCR), and then the viral concentrations in the positive samples were quantified by quantitative PCR (qPCR). Additionally, HAdV and HPyV genotyping was also performed by PCR. A total of 38/60 (63.3%) positive samples were found. HAdV was the most prevalent virus (26/60; 43.3%), followed by HPyV (21/60; 35%) and HPV (21/60; 35%). The viral concentrations ranged from 3.56 × 10 to 7.55 × 10 genome copies/L. The most common dual viral agents was found between HAdV and HPyV, in eight samples (8/38, 21%). HAdV types 40 and 41 as well as HPyV types JC and BK were identified, with HAdV-40 and HPyV JC being the most prevalent types. Furthermore, the detection rates of HAdV, HPyV, and HPV were higher during the winter season than the other seasons. The high prevalence of HAdV and HPyV supports their suitability as viral indicators of sewage contamination. Furthermore, this study demonstrates the advantages of environmental surveillance as a tool to elucidate the community-circulating viruses.
Topics: Humans; Adenoviridae; Sewage; Polyomavirus; Papillomavirus Infections; Adenoviruses, Human
PubMed: 38421633
DOI: 10.2166/wh.2024.322 -
CNS Neuroscience & Therapeutics Feb 2024Glucocorticoids (GCs) are steroidal hormones produced by the adrenal cortex. A physiological-level GCs have a crucial function in maintaining many cognitive processes,...
BACKGROUND
Glucocorticoids (GCs) are steroidal hormones produced by the adrenal cortex. A physiological-level GCs have a crucial function in maintaining many cognitive processes, like cognition, memory, and mood, however, both insufficient and excessive GCs impair these functions. Although this phenomenon could be explained by the U-shape of GC effects, the underlying mechanisms are still not clear. Therefore, understanding the underlying mechanisms of GCs may provide insight into the treatments for cognitive and mood-related disorders.
METHODS
Consecutive administration of corticosterone (CORT, 10 mg/kg, i.g.) proceeded for 28 days to mimic excessive GCs condition. Adrenalectomy (ADX) surgery was performed to ablate endogenous GCs in mice. Microinjection of 1 μL of Ad-mTERT-GFP virus into mouse hippocampus dentate gyrus (DG) and behavioral alterations in mice were observed 4 weeks later.
RESULTS
Different concentrations of GCs were shown to affect the cell growth and development of neural stem cells (NSCs) in a U-shaped manner. The physiological level of GCs (0.01 μM) promoted NSC proliferation in vitro, while the stress level of GCs (10 μM) inhibited it. The glucocorticoid synthesis blocker metyrapone (100 mg/kg, i.p.) and ADX surgery both decreased the quantity and morphological development of doublecortin (DCX)-positive immature cells in the DG. The physiological level of GCs activated mineralocorticoid receptor and then promoted the production of telomerase reverse transcriptase (TERT); in contrast, the stress level of GCs activated glucocorticoid receptor and then reduced the expression of TERT. Overexpression of TERT by AD-mTERT-GFP reversed both chronic stresses- and ADX-induced deficiency of TERT and the proliferation and development of NSCs, chronic stresses-associated depressive symptoms, and ADX-associated learning and memory impairment.
CONCLUSION
The bidirectional regulation of TERT by different GCs concentrations is a key mechanism mediating the U-shape of GC effects in modulation of hippocampal NSCs and associated brain function. Replenishment of TERT could be a common treatment strategy for GC dysfunction-associated diseases.
Topics: Mice; Animals; Glucocorticoids; Hippocampus; Corticosterone; Neural Stem Cells; Memory Disorders
PubMed: 38421107
DOI: 10.1111/cns.14577 -
Journal of Clinical Virology : the... Apr 2024BK Polyomavirus is of particular concern for kidney transplant recipients, due to their immunosuppression. This problem is exacerbated by the high effectiveness of... (Review)
Review
BK Polyomavirus is of particular concern for kidney transplant recipients, due to their immunosuppression. This problem is exacerbated by the high effectiveness of antirejection therapies, which also compromise the organism's ability to fight viral infections. The long-term risk is loss of graft function through BKPyV-associated nephropathy (BKPyVAN). The assessment of host immunity and its link to the control of viral infections is a major challenge. In terms of humoral immunity, researchers have highlighted the prognostic value of the pre-transplantation anti-BKPyV immunoglobulin G titer. However, humoral immunity alone does not guarantee viral clearance, and the correlation between the humoral response and the time course of the infection remains weak. In contrast, cellular immunity variables appear to be more closely associated with viral clearance, given that the cellular immune response to the kidney transplant is the main target of immunosuppressive treatments in recipients. However, the assessment of the cellular immune response to BK Polyomavirus is complex, and many details still need to be characterized. Here, we review the current state of knowledge about BKPyV cellular immunity, as well as the difficulties that may be encountered in studying it in kidney transplant recipient. This is an essential area of research for optimizing the management of transplant recipients and minimizing the risks associated with insidious BKPyV disease.
Topics: Humans; Kidney Transplantation; BK Virus; Transplant Recipients; Polyomavirus Infections; Kidney Diseases; Tumor Virus Infections
PubMed: 38412681
DOI: 10.1016/j.jcv.2024.105656 -
Future Microbiology Mar 2024A large proportion of the world's population is infected with HSV-1. Antiviral CD8 T cells and CD8α dendritic cells are closely related to HSV-1 infection and latency.... (Review)
Review
A large proportion of the world's population is infected with HSV-1. Antiviral CD8 T cells and CD8α dendritic cells are closely related to HSV-1 infection and latency. Latency-associated transcript of HSV-1 and PD-1 are involved in the regulation of latency and reactivation of HSV-1. Here, the role of latency-associated transcript, PD-1, CD8 T cells and CD8α dendritic cells in HSV-1 infection, the inter-relationships between them and how these interactions lead to latency are discussed, possibly providing new ideas for the treatment of HSV-1 infection.
Topics: Humans; CD8-Positive T-Lymphocytes; Programmed Cell Death 1 Receptor; Virus Latency; Herpes Simplex; Herpesvirus 1, Human
PubMed: 38411117
DOI: 10.2217/fmb-2023-0151 -
Future Microbiology 2024Ferroptosis, known as a type of programmed cell death that is iron dependent, is characterized by intracellular iron accumulation, glutathione depletion, glutathione... (Review)
Review
Ferroptosis, known as a type of programmed cell death that is iron dependent, is characterized by intracellular iron accumulation, glutathione depletion, glutathione peroxidase inactivation and lipid peroxidation. More and more research in recent years has demonstrated the tight connection between viral infections and ferroptosis. This article reviews the potential role and mechanism of ferroptosis in viral infection, and these findings will help in the prevention and treatment of the virus.
Topics: Ferroptosis; Humans; Virus Diseases; Iron; Lipid Peroxidation; Animals; Glutathione; Glutathione Peroxidase; Antiviral Agents
PubMed: 38411103
DOI: 10.2217/fmb-2023-0186 -
JAMA Network Open Feb 2024Sepsis is a leading cause of pediatric mortality. Little attention has been paid to the association between viral DNA and mortality in children and adolescents with...
IMPORTANCE
Sepsis is a leading cause of pediatric mortality. Little attention has been paid to the association between viral DNA and mortality in children and adolescents with sepsis.
OBJECTIVE
To assess the association of the presence of viral DNA with sepsis-related mortality in a large multicenter study.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study compares pediatric patients with and without plasma cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), human herpesvirus 6 (HHV-6), parvovirus B19 (B19V), BK polyomavirus (BKPyV), human adenovirus (HAdV), and torque teno virus (TTV) DNAemia detected by quantitative real-time polymerase chain reaction or plasma IgG antibodies to CMV, EBV, HSV-1, or HHV-6. A total of 401 patients younger than 18 years with severe sepsis were enrolled from 9 pediatric intensive care units (PICUs) in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Data were collected from 2015 to 2018. Samples were assayed from 2019 to 2022. Data were analyzed from 2022 to 2023.
MAIN OUTCOMES AND MEASURES
Death while in the PICU.
RESULTS
Among the 401 patients included in the analysis, the median age was 6 (IQR, 1-12) years, and 222 (55.4%) were male. One hundred fifty-four patients (38.4%) were previously healthy, 108 (26.9%) were immunocompromised, and 225 (56.1%) had documented infection(s) at enrollment. Forty-four patients (11.0%) died in the PICU. Viral DNAemia with at least 1 virus (excluding TTV) was detected in 191 patients (47.6%) overall, 63 of 108 patients (58.3%) who were immunocompromised, and 128 of 293 (43.7%) who were not immunocompromised at sepsis onset. After adjustment for age, Pediatric Risk of Mortality score, previously healthy status, and immunocompromised status at sepsis onset, CMV (adjusted odds ratio [AOR], 3.01 [95% CI, 1.36-6.45]; P = .007), HAdV (AOR, 3.50 [95% CI, 1.46-8.09]; P = .006), BKPyV (AOR. 3.02 [95% CI, 1.17-7.34]; P = .02), and HHV-6 (AOR, 2.62 [95% CI, 1.31-5.20]; P = .007) DNAemia were each associated with increased mortality. Two or more viruses were detected in 78 patients (19.5%), with mortality among 12 of 32 (37.5%) who were immunocompromised and 9 of 46 (19.6%) who were not immunocompromised at sepsis onset. Herpesvirus seropositivity was common (HSV-1, 82 of 246 [33.3%]; CMV, 107 of 254 [42.1%]; EBV, 152 of 251 [60.6%]; HHV-6, 253 if 257 [98.4%]). After additional adjustment for receipt of blood products in the PICU, EBV seropositivity was associated with increased mortality (AOR, 6.10 [95% CI, 1.00-118.61]; P = .049).
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that DNAemia for CMV, HAdV, BKPyV, and HHV-6 and EBV seropositivity were independently associated with increased sepsis mortality. Further investigation of the underlying biology of these viral DNA infections in children with sepsis is warranted to determine whether they only reflect mortality risk or contribute to mortality.
Topics: Adolescent; Humans; Male; Child; Infant; Child, Preschool; Female; DNA, Viral; Cohort Studies; Epstein-Barr Virus Infections; Herpesvirus 4, Human; DNA Viruses; Sepsis; Herpesvirus 1, Human; Cytomegalovirus Infections
PubMed: 38407904
DOI: 10.1001/jamanetworkopen.2024.0383 -
Frontiers in Pediatrics 2023BK virus-associated hemorrhagic cystitis (BK-HC) is a debilitating and poorly understood complication of hematopoietic stem cell transplantation (SCT). Hematuria,...
INTRODUCTION
BK virus-associated hemorrhagic cystitis (BK-HC) is a debilitating and poorly understood complication of hematopoietic stem cell transplantation (SCT). Hematuria, dysuria, and other symptoms associated with BK-HC are common in the immediate post-SCT period, making BK-HC difficult to distinguish from other conditions presenting with these symptoms. Despite published criteria for diagnosis, the degree to which these criteria are consistently applied to either clinical diagnosis or to studies informing BK-HC management is unclear. We present a case of BK-HC in a pediatric SCT recipient, and discuss the challenges associated with treatment in the absence of rigorous data to inform clinical management.
METHODS
We reviewed all cases of BK viruria at our center in patients undergoing SCT between January 2015 and December 2019. We then performed a scoping review of publications in PubMed addressing BK-HC, specifically focusing on how BK-HC was defined. Publications using the keywords "BK polyomavirus" and "hemorrhagic cystitis" were included if they involved a clinical study of SCT recipients and a full-text article was available in English. Case reports were excluded. Analysis focused on whether BK-HC was explicitly defined and whether the definition incorporated elements of diagnostic criteria published by European Conference on Infections in Leukemia (ECIL).
RESULTS
A total of 30 studies published between January 2018 and 30 June 2021 met criteria for review, including 4 clinical trials, 7 prospective observational studies, and 19 retrospective observational studies. Fifteen of these studies included pediatric patients (7 pediatric only, 8 combined adult and pediatric). Of the 30 publications, 19 included a definition of either BK-HC or BK cystitis, with only five using ECIL criteria, all of which were observational studies. Multiple interventions are described for treatment of BK-HC, including cidofovir, leflunomide, quinolones, hyperbaric oxygen, keratinocyte growth factor, and BK-specific cytotoxic T lymphocytes. However, evidence to support efficacy for any of these interventions is lacking.
DISCUSSION
Although BK-HC is a well-known complication of SCT, evidence to support available treatment options is limited. Well-controlled studies that incorporate clear diagnostic criteria are needed to better define the risk factors, natural history, and ideal interventions.
PubMed: 38406625
DOI: 10.3389/fped.2023.1267678