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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 -
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 -
BMC Urology Apr 2024JC polyomavirus (JCPyV) is a human polyomavirus that can establish lifelong persistent infection in the majority of adults. It is typically asymptomatic in...
JC polyomavirus (JCPyV) is a human polyomavirus that can establish lifelong persistent infection in the majority of adults. It is typically asymptomatic in immunocompetent individuals. However, there is a risk of developing progressive multifocal leukoencephalopathy (PML) in immunocompromised or immunosuppressed patients. Though JCPyV commonly resides in the kidney-urinary tract, its involvement in urinary system diseases is extremely rare. Here, we reported a case of a 60-year-old male patient with coronavirus disease 2019 (COVID-19) infection who developed hemorrhagic cystitis after receiving treatment with nirmatrelvir 300 mg/ritonavir 100 mg quaque die (QD). Subsequent metagenomic next-generation sequencing (mNGS) confirmed the infection to be caused by JCPyV type 2. Then, human immunoglobulin (PH4) for intravenous injection at a dose of 25 g QD was administered to the patient. Three days later, the hematuria resolved. This case illustrates that in the setting of compromised host immune function, JCPyV is not limited to causing central nervous system diseases but can also exhibit pathogenicity in the urinary system. Moreover, mNGS technology facilitates rapid diagnosis of infectious etiology by clinical practitioners, contributing to precise treatment for patients.
Topics: Humans; Male; Middle Aged; COVID-19; Cystitis, Hemorrhagic; JC Virus; Leukoencephalopathy, Progressive Multifocal; Polyomavirus Infections
PubMed: 38627797
DOI: 10.1186/s12894-024-01464-1 -
BioRxiv : the Preprint Server For... Apr 2024Ebola virus (EBOV) is a high-consequence filovirus that gives rise to frequent epidemics with high case fatality rates and few therapeutic options. Here, we applied...
Ebola virus (EBOV) is a high-consequence filovirus that gives rise to frequent epidemics with high case fatality rates and few therapeutic options. Here, we applied image-based screening of a genome-wide CRISPR library to systematically identify host cell regulators of Ebola virus infection in 39,085,093 million single cells. Measuring viral RNA and protein levels together with their localization in cells identified over 998 related host factors and provided detailed information about the role of each gene across the virus replication cycle. We trained a deep learning model on single-cell images to associate each host factor with predicted replication steps, and confirmed the predicted relationship for select host factors. Among the findings, we showed that the mitochondrial complex III subunit UQCRB is a post-entry regulator of Ebola virus RNA replication, and demonstrated that UQCRB inhibition with a small molecule reduced overall Ebola virus infection with an IC50 of 5 μM. Using a random forest model, we also identified perturbations that reduced infection by disrupting the equilibrium between viral RNA and protein. One such protein, STRAP, is a spliceosome-associated factor that was found to be closely associated with VP35, a viral protein required for RNA processing. Loss of STRAP expression resulted in a reduction in full-length viral genome production and subsequent production of non-infectious virus particles. Overall, the data produced in this genome-wide high-content single-cell screen and secondary screens in additional cell lines and related filoviruses (MARV and SUDV) revealed new insights about the role of host factors in virus replication and potential new targets for therapeutic intervention.
PubMed: 38617272
DOI: 10.1101/2024.04.06.588168 -
Nature Communications Apr 2024Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory... (Randomized Controlled Trial)
Randomized Controlled Trial
Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent influenza vaccination in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic (pH1N1) and monitored for infection. We found that seasonal vaccination increases pH1N1 specific antibodies and FcR effector functions. Furthermore, prospective baseline antibody profiles after seasonal vaccination, prior to pH1N1 infection, show that unvaccinated uninfected children have elevated ADCC effector function, FcγR3a and FcγR2a binding antibodies to multiple pH1N1 proteins, past seasonal and avian (H5, H7 and H9) strains. Whereas, children that became pH1N1 infected after seasonal vaccination have antibodies focussed to seasonal strains without FcR functions, and greater aggregated HA-specific profiles for IgM and IgG3. Modeling to predict infection susceptibility, ranked baseline hemagglutination antibody inhibition as the highest contributor to lack of pH1N1 infection, in combination with features that include pH1-IgG1, H1-stem responses and FcR binding to seasonal vaccine and pH1 proteins. Thus, seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive antibodies with Fc potential without vaccination and may be considered 'elite influenza controllers'.
Topics: Child; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Prospective Studies; Antibodies, Viral; Antibodies, Neutralizing; Immunoglobulin G; Influenza Vaccines
PubMed: 38615070
DOI: 10.1038/s41467-024-47590-0 -
Neurology(R) Neuroimmunology &... May 2024Epstein-Barr virus (EBV) infection is a major risk factor of multiple sclerosis (MS). We examined the presence of EBV DNA in the CSF and blood of patients with MS and...
BACKGROUND AND OBJECTIVES
Epstein-Barr virus (EBV) infection is a major risk factor of multiple sclerosis (MS). We examined the presence of EBV DNA in the CSF and blood of patients with MS and controls. We analyzed whether EBV DNA is more common in the CSF of patients with MS than in controls and estimated the proportions of EBV-positive B cells in the CSF and blood.
METHODS
CSF supernatants and cells were collected at diagnostic lumbar punctures from 45 patients with MS and 45 HLA-DR15 matched controls with other conditions, all participants were EBV seropositive. Cellular DNA was amplified by Phi polymerase targeting both host and viral DNA, and representative samples were obtained in 28 cases and 28 controls. Nonamplified DNA from CSF cells (14 cases, 14 controls) and blood B cells (10 cases, 10 controls) were analyzed in a subset of participants. Multiple droplet digital PCR (ddPCR) runs were performed per sample to assess the cumulative EBV positivity rate. To detect viral RNA as a sign of activation, RNA sequencing was performed in blood CD4-positive, CD8-positive, and CD19-positive cells from 21 patients with MS and 3 controls.
RESULTS
One of the 45 patients with MS and none of the 45 controls were positive for EBV DNA in CSF supernatants (1 mL). CSF cellular DNA was analyzed in 8 independent ddPCRs: EBV DNA was detected at least once in 18 (64%) of the 28 patients with MS and in 15 (54%) of the 28 controls ( = 0.59, Fisher test). The cumulative EBV positivity increased steadily up to 59% in the successive ddPCRs, suggesting that all individuals would have reached EBV positivity in the CSF cells, if more DNA would have been analyzed. The estimated proportion of EBV-positive B cells was >1/10,000 in both the CSF and blood. We did not detect viral RNA, except from endogenous retroviruses, in the blood lymphocyte subpopulations.
DISCUSSION
EBV-DNA is equally detectable in the CSF cells of both patients with MS and controls with ddPCR, and the probabilistic approach indicates that the true positivity rate approaches 100% in EBV-positive individuals. The proportion of EBV-positive B cells seems higher than previously estimated.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Multiple Sclerosis; DNA, Viral; RNA, Viral
PubMed: 38608226
DOI: 10.1212/NXI.0000000000200226 -
Molecular Therapy. Oncology Mar 2024Oncolytic herpes simplex viruses (oHSVs) have emerged as leading cancer therapeutic agents. Effective oHSV virotherapy may ultimately require both intratumoral and...
Oncolytic herpes simplex viruses (oHSVs) have emerged as leading cancer therapeutic agents. Effective oHSV virotherapy may ultimately require both intratumoral and systemic vector administration to target the primary tumor and distant metastases. An attractive approach to enhancing oHSV tumor specificity is engineering the virus envelope glycoproteins for selective recognition of and infection via tumor-specific cell surface proteins. We previously demonstrated that oHSVs could be retargeted to EGFR-expressing cells by the incorporation of a single-chain antibody (scFv) at the N terminus of glycoprotein D (gD). Here, we compared retargeted oHSVs generated by the insertion of scFv, affibody molecule, or VHH antibody ligands at different positions within the N terminus of gD. When compared to the scFv-directed oHSVs, VHH and affibody molecules mediated enhanced EGFR-specific tumor cell entry, spread and cell killing , and enabled long-term tumor-specific virus replication following intravenous delivery . Moreover, oHSVs retargeted via a VHH ligand reduced tumor growth upon intravenous injection and achieved complete tumor destruction after intratumoral injection. Systemic oHSV delivery is important for the treatment of metastatic disease, and our enhancements in targeted oHSV design are a critical step in creating an effective tumor-specific oHSVs for safe administration via the bloodstream.
PubMed: 38596286
DOI: 10.1016/j.omton.2024.200761 -
Kidney Medicine May 2024
PubMed: 38595735
DOI: 10.1016/j.xkme.2024.100807 -
Decreased risk of non-influenza respiratory infection after influenza B virus infection in children.Epidemiology and Infection Apr 2024Previous studies suggest that influenza virus infection may provide temporary non-specific immunity and hence lower the risk of non-influenza respiratory virus... (Randomized Controlled Trial)
Randomized Controlled Trial
Previous studies suggest that influenza virus infection may provide temporary non-specific immunity and hence lower the risk of non-influenza respiratory virus infection. In a randomized controlled trial of influenza vaccination, 1 330 children were followed-up in 2009-2011. Respiratory swabs were collected when they reported acute respiratory illness and tested against influenza and other respiratory viruses. We used Poisson regression to compare the incidence of non-influenza respiratory virus infection before and after influenza virus infection. Based on 52 children with influenza B virus infection, the incidence rate ratio (IRR) of non-influenza respiratory virus infection after influenza virus infection was 0.47 (95% confidence interval: 0.27-0.82) compared with before infection. Simulation suggested that this IRR was 0.87 if the temporary protection did not exist. We identified a decreased risk of non-influenza respiratory virus infection after influenza B virus infection in children. Further investigation is needed to determine if this decreased risk could be attributed to temporary non-specific immunity acquired from influenza virus infection.
Topics: Child; Humans; Influenza, Human; Orthomyxoviridae Infections; Orthomyxoviridae; Influenza B virus; Herpesviridae Infections; Influenza Vaccines; Respiratory Tract Infections
PubMed: 38584132
DOI: 10.1017/S0950268824000542 -
Discovery Immunology 2024Influenza virus represents a challenge for traditional vaccine approaches due to its seasonal changes and potential for zoonotic transmission. Nucleic acid vaccines can...
Influenza virus represents a challenge for traditional vaccine approaches due to its seasonal changes and potential for zoonotic transmission. Nucleic acid vaccines can overcome some of these challenges, especially through the inclusion of multiple antigens to increase the breadth of response. RNA vaccines were an important part of the response to the COVID-19 pandemic, but for future outbreaks DNA vaccines may have some advantages in terms of stability and manufacturing cost that warrant continuing investigation to fully realize their potential. Here, we investigate influenza virus vaccines made using a closed linear DNA platform, Doggybone™ DNA (dbDNA), produced by a rapid and scalable cell-free method. Influenza vaccines have mostly focussed on Haemagglutinin (HA), but the inclusion of Neuraminidase (NA) may provide additional protection. Here, we explored the potential of including NA in a dbDNA vaccine, looking at DNA optimization, mechanism and breadth of protection. We showed that DNA targeting sequences (DTS) improved immune responses against HA but not NA. We explored whether NA vaccine-induced protection against influenza virus infection was cell-mediated, but depletion of CD8 and NK cells made no impact, suggesting it was antibody-mediated. This is reflected in the restriction of protection to homologous strains of influenza virus. Importantly, we saw that including both HA and NA in a single combined vaccine did not dampen the immune response to either one. Overall, we show that linear dbDNA can induce an immune response against NA, which may offer increased protection in instances of HA mismatch where NA remains more conserved.
PubMed: 38567290
DOI: 10.1093/discim/kyad030