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Viruses Aug 2022Senecavirus A (SVA) is a member of the family and enzootic in domestic swine. SVA can induce vesicular lesions that are clinically indistinguishable from Foot-and-mouth...
Senecavirus A (SVA) is a member of the family and enzootic in domestic swine. SVA can induce vesicular lesions that are clinically indistinguishable from Foot-and-mouth disease, a major cause of global trade barriers and agricultural productivity losses worldwide. The LF-BK αβ cell line is a porcine-derived cell line transformed to stably express an αβ bovine integrin and primarily used for enhanced propagation of Foot-and-mouth disease virus (FMDV). Due to the high biosecurity requirements for working with FMDV, SVA has been considered as a surrogate virus to test and evaluate new technologies and countermeasures. Herein we conducted a series of comparative evaluation in vitro studies between SVA and FMDV using the LF-BK αβ cell line. These include utilization of LF-BK αβ cells for field virus isolation, production of high virus titers, and evaluating serological reactivity and virus susceptibility to porcine type I interferons. These four methodologies utilizing LF-BK αβ cells were applicable to research with SVA and results support the current use of SVA as a surrogate for FMDV.
Topics: Animals; Cattle; Cell Line; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Integrins; Interferon Type I; Picornaviridae; Swine; Swine Diseases
PubMed: 36146682
DOI: 10.3390/v14091875 -
Viruses Mar 2021BK polyomavirus nephropathy (BKVN) and allograft rejection are two closely-associated diseases on opposite ends of the immune scale in kidney transplant recipients. The... (Review)
Review
BK polyomavirus nephropathy (BKVN) and allograft rejection are two closely-associated diseases on opposite ends of the immune scale in kidney transplant recipients. The principle of balancing the immune system remains the mainstay of therapeutic strategy. While patient outcomes can be improved through screening, risk factors identification, and rapid reduction of immunosuppressants, a lack of standard curative therapy is the primary concern during clinical practice. Additionally, difficulty in pathological differential diagnosis and clinicopathology's dissociation pose problems for a definite diagnosis. This article discusses the delicate evaluation needed to optimize immunosuppression and reviews recent advances in molecular diagnosis and immunological therapy for BKVN patients. New biomarkers for BKVN diagnosis are under development. For example, measurement of virus-specific T cell level may play a role in steering immunosuppressants. The development of cellular therapy may provide prevention, even a cure, for BKVN, a complex post-transplant complication.
Topics: BK Virus; Graft Rejection; Humans; Immunosuppression Therapy; Kidney Diseases; Kidney Transplantation; Polyomavirus Infections; Transplant Recipients; Tumor Virus Infections
PubMed: 33809472
DOI: 10.3390/v13030487 -
Frontiers in Nephrology 2022Kidney transplantation in HIV-infected individuals with end-stage kidney disease is associated with improved survival compared to dialysis. Rabbit anti-thymocyte...
BACKGROUND
Kidney transplantation in HIV-infected individuals with end-stage kidney disease is associated with improved survival compared to dialysis. Rabbit anti-thymocyte globulin (rATG) induction in HIV-infected kidney transplant recipients has been associated with a lower risk of acute rejection, but data on the rates of malignancy and BK viremia in these patients is lacking.
METHODS
We performed a single-center retrospective cohort study of adult HIV-infected individuals who underwent kidney transplantation with rATG induction between January 2006 and December 2016. The primary outcome was the development of malignancy. Secondary outcomes included the development of BK viremia, infections requiring hospitalization, HIV progression, biopsy-proven acute rejection, and patient and allograft survival.
RESULTS
Twenty-seven HIV-infected individuals with end-stage kidney disease received deceased (n=23) or living (n=4) donor kidney transplants. The cumulative rate of malignancy at five years was 29%, of whom 29% died because of advanced malignancy. BK viremia was detected in six participants (22%), of whom one had biopsy-proven BK virus-associated nephropathy and all of whom cleared the BK viremia. Five-year acute rejection rates, patient survival and death-censored allograft survival were 17%, 85% and 80% respectively.
CONCLUSION
rATG induction in HIV-infected kidney transplant recipients was associated with a low risk of acute rejection, but a potentially higher risk of malignancies and BK viremia in this cohort. Screening strategies to closely monitor for BK virus infection and malignancy post-transplantation may improve outcomes in HIV-infected kidney transplant recipients receiving rATG induction.
PubMed: 37675034
DOI: 10.3389/fneph.2022.1047170 -
Viruses Oct 2020Polyomaviruses are small, non-enveloped DNA tumor viruses that cause serious disease in immunosuppressed people, including progressive multifocal leukoencephalopathy...
Polyomaviruses are small, non-enveloped DNA tumor viruses that cause serious disease in immunosuppressed people, including progressive multifocal leukoencephalopathy (PML) in patients infected with JC polyomavirus, but the molecular events mediating polyomavirus entry are poorly understood. Through genetic knockdown approaches, we identified phosphoinositide 3'-kinase γ (PI3Kγ) and its regulatory subunit PIK3R5 as cellular proteins that facilitate infection of human SVG-A glial cells by JCPyV. PI3Kα appears less important for polyomavirus infection than PI3Kγ. CRISPR/Cas9-mediated knockout of PIK3R5 or PI3Kγ inhibited infection by authentic JCPyV and by JC pseudovirus. PI3Kγ knockout also inhibited infection by BK and Merkel Cell pseudoviruses, other pathogenic human polyomaviruses, and SV40, an important model polyomavirus. Reintroduction of the wild-type gene into the PI3Kγ knock-out SVG-A cells rescued the JCPyV infection defect. Disruption of the PI3Kγ pathway did not block binding of JCPyV to cells or virus internalization, implying that PI3Kγ facilitates some intracellular step(s) of infection. These results imply that agents that inhibit PI3Kγ signaling may have a role in managing polyomavirus infections.
Topics: Cell Line; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Neuroglia; Phosphatidylinositol 3-Kinases; Phosphatidylinositols; Polyomavirus; Polyomavirus Infections; Virus Internalization
PubMed: 33092168
DOI: 10.3390/v12101190 -
Frontiers in Cellular and Infection... 2022BK polyomavirus infection results in renal allograft dysfunction, and it is important to find methods of prediction and treatment. As a regulator of host immunity,...
BACKGROUND
BK polyomavirus infection results in renal allograft dysfunction, and it is important to find methods of prediction and treatment. As a regulator of host immunity, changes in the gut microbiota are associated with a variety of infections. However, the correlation between microbiota dysbiosis and posttransplant BK polyomavirus infection was rarely studied. Thus, this study aimed to characterize the gut microbiota in BK polyomavirus-infected renal transplant recipients in order to explore the biomarkers that might be potential therapeutic targets and establish a prediction model for posttransplant BK polyomavirus infection based on the gut microbiota.
METHODS
We compared the gut microbial communities of 25 BK polyomavirus-infected renal transplant recipients with 23 characteristic-matched controls, applying the 16S ribosomal RNA gene amplicon sequencing technique.
RESULTS
At the phylum level, / ratio significantly increased in the BK polyomavirus group. was positively correlated with CD4/CD8 ratio. In the top 20 dominant genera, and exhibited a significant difference between the two groups. No significant difference was observed in microbial alpha diversity. Beta diversity revealed a significant difference between the two groups. Nine distinguishing bacterial taxa were discovered between the two groups. We established a random forest model using genus taxa to predict BK polyomavirus infectious status, which achieved the best accuracy (80.71%) with an area under the curve of 0.82. Two genera were included in the best model, which were and .
CONCLUSIONS
BK polyomavirus-infected patients had gut microbiota dysbiosis in which the / ratio increased in the course of the viral infection. Nine distinguishing bacterial taxa might be potential biomarkers of BK polyomavirus infection. The random forest model achieved an accuracy of 80.71% in predicting the BKV infectious status, with and included.
Topics: BK Virus; Biomarkers; Case-Control Studies; Dysbiosis; Gastrointestinal Microbiome; Humans; Kidney Transplantation; Polyomavirus Infections
PubMed: 35694540
DOI: 10.3389/fcimb.2022.860201 -
American Journal of Blood Research 2020Hematopoietic stem cell transplantation (HSCT) represents a vital curative choice for many disease. However its outcome can be hampered by a variety of transplant... (Review)
Review
Hematopoietic stem cell transplantation (HSCT) represents a vital curative choice for many disease. However its outcome can be hampered by a variety of transplant associated complications. Hemorrhagic cystitis (HC) considered as one of the major difficulties after HSCT. HC symptoms comprise hematuria, dysuria, burning during urination, urinary frequency, urgency and incontinency, abdominal or suprapubic pain, urinary obstruction, and renal or bladder damage. There are a lot of causes for HC development. BK virus reactivation is one of the major causes of HC after HSCT. There is still no standard and approved treatment protocol for BK virus associated HC (BKV-HC). Treatment of HC is according to the local standard operating procedures, depending on the cause and severity. In this study we will review the current treatments available for this disease. We have divided the therapeutic procedures into 5 categories including conservative therapy, complimentary options, surgical procedures, pharmacological treatments and adoptive cell therapy. We believe that comparing the advantages and disadvantages of different therapies make it easier to choose the best treatment protocol. In addition, we had a greater focus on adoptive cell therapy, because it is a relatively new introduced method and might be a logical alternative to conventional treatments for refractory patients. In total, no definitive recommendation is possible for current available treatments because these procedures have only been utilized sporadically in a limit number of patients. Furthermore, a number of treatment options are only experimental and definitely need more effort.
PubMed: 33224566
DOI: No ID Found -
Blood Advances May 2020Clinical disease caused by BK virus reactivation is a frequent complication of allogeneic hematopoietic cell transplantation (HCT). Because of the lack of effective...
Clinical disease caused by BK virus reactivation is a frequent complication of allogeneic hematopoietic cell transplantation (HCT). Because of the lack of effective antiviral agents, BK virus-specific T cells are emerging as a potential therapy for BK virus disease, but the immune response to BK virus after allogeneic HCT has not been well characterized. Our study describes reconstitution of BK virus-specific T-cell immunity in 77 adult patients after HCT. All patients had urinary symptoms, and urine was tested for BK virus replication; 33 patients were positive for BK virus (cases), and 44 were negative (controls). In BK virus cases, the median time to first positive test was 75 days (range, 2-511). BK virus cases had lower CD4 T-cell counts 3 to 9 months after transplant, but CD8 T-cell counts were similar in cases and controls. BK virus-specific T cells were identified by cytokine flow cytometry in cryopreserved samples collected prospectively. BK virus-specific CD4 T cells producing T helper 1 (Th1) cytokines recovered quickly after HCT. BK virus-specific T cells were detected more frequently in patients with BK virus reactivation at most time points, and CD4 T cells producing Th1 cytokines were more frequent than BK virus-specific cytolytic CD8 T cells. Early detection of interferon-γ+ and cytolytic BK virus-specific CD4 T cells was associated with lower rates of hematuria among cases. Overall, our study describes recovery of BK virus-specific T cells after HCT and the distinct roles for BK virus-specific T cells in the development and resolution of clinical symptoms.
Topics: Adult; BK Virus; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Hematopoietic Stem Cell Transplantation; Humans; Immune Reconstitution
PubMed: 32374880
DOI: 10.1182/bloodadvances.2019001120 -
Scientific Reports Aug 2023BK polyomavirus (BKPyV) is a human DNA virus that resides latent in the host's renal tissue. Reactivation occurs occasionally and in case of kidney transplantation, it...
BK polyomavirus (BKPyV) is a human DNA virus that resides latent in the host's renal tissue. Reactivation occurs occasionally and in case of kidney transplantation, it can lead to polyomavirus-associated nephropathy (PVAN). Due to the lack of specific antivirals for BKPyV and despite the risk of allograft rejection, reduction of immunosuppression remains the main approach for treating PVAN. Current data suggests that mutations can accumulate over time in the major capsid protein VP1 and can lead to neutralization escape in kidney transplant recipients. Herein, we show that mutations occur throughout the entire BKPyV genome, including in VP1. Changes were identified by per-patient comparison of viral genome sequences obtained in samples from 32 kidney recipients with persistent viremia collected at different post-transplant time-points. Amino acid changes were observed in both earlier and later post-transplant samples, although some of them were only found in later samples. Changes in VP1 mainly consisted in the introduction of a new amino acid. A switch back to the conservative amino acid was also observed. This should be considered in future approaches for treating BKPyV infection in kidney transplant recipients.
Topics: Humans; BK Virus; Viremia; Kidney Transplantation; Polyomavirus; Amino Acids
PubMed: 37598256
DOI: 10.1038/s41598-023-40714-4 -
Indian Journal of Pathology &... Nov 2023The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate...
BACKGROUND
The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate the bacterial and viral etiological diagnosis of ME in children less than 5 years of age.
MATERIAL AND METHODS
The present study was conducted in Virus Research and Diagnostic Laboratory (VRDL), Department of Microbiology, King George's Medical University, Lucknow, from July 2020 to June 2022. Serum, cerebrospinal fluid (CSF), and nose/throat swabs were collected from all the enrolled cases of meningoencephalitis in children below 5 years of age and tested for various etiological agents by ELISA and/or real-time PCR.
RESULTS
Of 130 enrolled cases, 50 (38.5%) cases tested positive for one or more etiological agents. Etiological agents of ME detected were Japanese encephalitis virus (JEV) (8.46%), adenovirus (6.92%), influenza virus (5.38%), dengue virus (3.85%), Parvo B-19 virus (3.08%), Orientia tsutsugamushi (3.08%), Herpes Simplex Virus-1 (HSV-1) (1.54%), measles virus (1.54%), and Varicella-Zoster Virus (VZV) (1.54%). Rubella virus, Chikungunya virus (CHKV), Mumps virus, Enteroviruses, Parecho virus, John Cunningham virus (JC), BK virus, Nipah virus, Kyasanur Forest Disease virus (KFD), Chandipura virus, Herpes Simplex Virus (HSV-2), SARS CoV-2, N. Meningitides, and H. Influenzae were tested but not detected in any of the cases.
CONCLUSION
We identified the etiological agents in 50/130 (38.5%) suspected ME cases in children less than 5 years of age, using molecular and ELISA-based diagnostic methods. The four most common pathogens detected were JEV, adenovirus, influenza virus, and dengue virus.
PubMed: 38394398
DOI: 10.4103/ijpm.ijpm_60_23 -
Experimental and Clinical... Feb 2021BK polyomavirus can infect healthy individuals; however, in renal transplant recipients, it can cause nephropathy, which can lead to renal allograftfailure. There are... (Comparative Study)
Comparative Study
OBJECTIVES
BK polyomavirus can infect healthy individuals; however, in renal transplant recipients, it can cause nephropathy, which can lead to renal allograftfailure. There are currently no effective antiviral agents against BK polyomavirus. Surveillance after kidney transplant for BK polyomavirus is the only means to prevent allograft failure. Transplant centers routinely screen for BK polyomavirus in either urine or blood. If BK polyomavirus replication occurs, itis usually detected first in urine, which is followed by detection in blood in a subset of cases. Screening for BK polyomavirus in urine has the potential for earlier detection of viralreactivation.However, not all patients with BK polyomavirus in urine will progress to BK viremia. Therefore, adding urine screening could increase the cost oftests without a clear clinical benefit.
MATERIALS AND METHODS
We conducted an analysis of BK polyomavirus screening methods at 2 different centers and compared their clinical outcomes and efficiency of testing.
RESULTS
We analyzed 209 patientswith BK polyomavirus reactivation after kidney transplant at 2 different institutions from 2008 to 2018. BK polyomavirus reactivation in blood was detected earlierifthe patient was screened by urine screening protocol. However, measurable clinical outcomes were similarin all groups with different screening methods.
CONCLUSIONS
Although screening for BK polyomavirus in urine did detect viralreactivation earlier,there were no differences in graft or clinical outcomes when either the urine or blood screening method was used.
Topics: BK Virus; Humans; Kidney; Kidney Transplantation; Polyomavirus Infections; Viremia; Virus Activation
PubMed: 31801449
DOI: 10.6002/ect.2019.0295