Development of a Recombinant Protein-Based Immunoassay for Detection of Antibodies Against Karolinska Institute and Washington University Polyomaviruses.

To develop polyomavirus VP1 recombinant protein-based immunoassay, the expression of two polyomavirus (Karolinska Institute Polyomavirus; KIPyV, and Washington University Polyomavirus; WUPyV) VP1s in insect cells was investigated using an improved baculovirus system (BacMagic). The reliability of the purified VP1 to serve as antigens in serological tests was confirmed by the establishment of an enzyme-linked immunosorbent assay (ELISA). Two panels of serum samples were used, with Panel I comprising 60 sera (20 KIPyV-positive, 20 WUPyV-positive, and 20 negative) and Panel II consisting of 134 sera with unknown status. The seroprevalence of KIPyV and WUPyV in the study population was determined to be 62% and 50%, respectively. Antibody-negative sera exhibited low reactivities in both ELISAs, whereas antibody-positive sera displayed high reactivity with median optical density values of 1.37 and 1.47 in the KIPyV and WUPyV ELISAs, respectively. The differences in seroreactivities between antibody positive and negative for each virus were statistically significant (p < 0.0001; with 95% confidence interval). The study suggests that seroconversion for KIPyV and WUPyV occurs in childhood, with KIPyV seropositivity reaching 70% and WUPyV seropositivity reaching 60% after the age of 5 years. Adult seroprevalence for polyomaviruses was high, with more than 64% and 51% of the adult population being seropositive for KIPyV and WUPyV, respectively. The constant prevalence of KIPyV and WUPyV antibody in the age groups suggested that this antibody persists for life. The fact that antibody titers were generally stable over time revealed a persistent infection of polyomaviruses in the human population. The insect cell-derived recombinant VP1-based ELISA has been demonstrated to be valuable as a serological assay, offering a valid, reliable, fast, nonlaborious, and economical procedure.

Corrigendum: The role of peroxisome proliferator-activated receptors in the modulation of hyperinflammation induced by SARS-CoV-2 infection: A perspective for COVID-19 therapy.

[This corrects the article DOI: 10.3389/fimmu.2023.1127358.].

Exosomal non-coding RNAs' role in immune regulation and potential therapeutic applications.

Exosomes are now significant players in both healthy and unhealthy cell-to-cell communication. Exosomes can mediate immune activation or immunosuppression, which can influence the growth of tumors. Exosomes affect the immune responses to malignancies in various ways by interacting with tumor cells and the environment around them. Exosomes made by immune cells can control the growth, metastasis, and even chemosensitivity of tumor cells. In contrast, exosomes produced by cancer cells can encourage immune responses that support the tumor. Exosomes carry circular RNAs, long non-coding RNAs, and microRNAs (miRNAs), all involved in cell-to-cell communication. In this review, we focus on the most recent findings concerning the role of exosomal miRNAs, lncRNAs, and circRNAs in immune modulation and the potential therapeutic implications of these discoveries.

The role of peroxisome proliferator-activated receptors in the modulation of hyperinflammation induced by SARS-CoV-2 infection: A perspective for COVID-19 therapy.

Coronavirus disease 2019 (COVID-19) is a severe respiratory disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that affects the lower and upper respiratory tract in humans. SARS-CoV-2 infection is associated with the induction of a cascade of uncontrolled inflammatory responses in the host, ultimately leading to hyperinflammation or cytokine storm. Indeed, cytokine storm is a hallmark of SARS-CoV-2 immunopathogenesis, directly related to the severity of the disease and mortality in COVID-19 patients. Considering the lack of any definitive treatment for COVID-19, targeting key inflammatory factors to regulate the inflammatory response in COVID-19 patients could be a fundamental step to developing effective therapeutic strategies against SARS-CoV-2 infection. Currently, in addition to well-defined metabolic actions, especially lipid metabolism and glucose utilization, there is growing evidence of a central role of the ligand-dependent nuclear receptors and peroxisome proliferator-activated receptors (PPARs) including PPARα, PPARß/δ, and PPARγ in the control of inflammatory signals in various human inflammatory diseases. This makes them attractive targets for developing therapeutic approaches to control/suppress the hyperinflammatory response in patients with severe COVID-19. In this review, we (1) investigate the anti-inflammatory mechanisms mediated by PPARs and their ligands during SARS-CoV-2 infection, and (2) on the basis of the recent literature, highlight the importance of PPAR subtypes for the development of promising therapeutic approaches against the cytokine storm in severe COVID-19 patients.

Combination therapy with nivolumab (anti-PD-1 monoclonal antibody): A new era in tumor immunotherapy.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1 or CD279) have noticeably improved the treatment landscape of advanced cancer patients. Nivolumab, the most well-known genetically engineered anti-PD-1 monoclonal antibody (mAb), promotes anti-tumor immunity and shows excellent capability for treating various cancers, particularly lung cancer, renal cancer, and melanoma. Systemic administration of nivolumab could inspire durable therapeutic responses not typically seen with traditional cytotoxic anti-cancer agents. However, nivolumab monotherapy is ineffective in 60-70 percent of patients. The mechanisms leading to both primary and acquired resistance to PD-1/PD-L1 inhibition are varied and multifactorial. Recently, the rationality of adding other conventional therapies such as chemo-radiotherapy and targeted therapies such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and VEGF/VEGFR inhibitors to nivolumab has strongly been verified. These regimens overcome cancer resistance and thus boost nivolumab efficacy in cancer patients. Herein, we discuss the current status of the combination therapy with nivolumab in cancer patients, with a particular focus on the recent clinical reports.

Recent advances in atezolizumab-based programmed death-ligand 1 (PD-L1) blockade therapy for breast cancer.

Breast cancer, the most common cancer in women worldwide, is curable in âˆ¼ 70-80 % of patients with early-stage, non-metastatic disorder. However, advanced breast cancer with distant organ metastases is incurable with available therapeutics. Thus, scientists have sought emerging strategies for treating metastatic breast cancers., Immune checkpoint inhibitors (ICIs) have represented a significant development in breast cancer immunotherapy. Now, targeting immune checkpoint molecules (e.g., programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1)) have attracted increasing attention in the context of breast cancer therapy, chiefly triple-negative breast cancer (TNBC). Atezolizumab, a humanized IgG1 monoclonal antibody (mAb), has been designed to interfere with the binding of the PD-L1 ligand to its receptor. Targeting PD-L1 using atezolizumab potentiates T-cell responses to the tumor and consequently boosts tumor responses. The results of the IMpassion130 trial have recently led to the approval of the combination of atezolizumab and nab-paclitaxel to treat unresectable locally advanced or metastatic patients with PD-L1-positive TNBC. Herein, we summarize the clinical efficacy of atezolizumab in treating breast cancer and briefly discuss the possible immune-related adverse events (irAEs).

Plant-mediated synthesis of silver-doped zinc oxide nanoparticles and evaluation of their antimicrobial activity against bacteria cause tooth decay.

In this research, silver-doped zinc oxide (SdZnO) nanoparticles (NPs) were synthesized in an environmental-friendly manner. The synthesized NPs were identified by UV-vis spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM). Finally, the antimicrobial activity of synthesized ZnO and SdZnO NPs was performed. It was observed that by doping silver, the size of ZnO NPs was changed. By adding silver to ZnO NPs, the antimicrobial effect of ZnO NPs was improved. Antibacterial test against gram-positive bacterium Streptococcus mutants showed that SdZnO NPs with a low density of silver had higher antibacterial activity than ZnO NPs; Therefore, SdZnO NPs can be used as a new antibacterial agent in medical applications. RESEARCH HIGHLIGHTS: Silver-doped zinc oxide nanoparticles were prepared using an eco-friendly synthesis method and their antimicrobial activity against bacteria causing tooth decay was studied.

Asymptomatic Herpes Simplex Virus Infection in Iranian Mothers and Their Newborns.

This study aims to determine the prevalence of herpes simplex virus (HSV) infection among pregnant women as well as congenital infection of their newborns in Tehran. One hundred samples of blood sera from pregnant women were analyzed for the presence of HSV specific antibodies. Umbilical cord blood samples from the newborns were analyzed for the presence of HSV DNA using real-time PCR. HSV IgG and IgM antibodies were found in 97% and 2% of pregnant women, respectively. Of all the 100 cord blood samples, 6 were positive for HSV DNA in which 2 cases were from mothers who had detectable IgM. It was notable that all corresponding mothers of six HSV positive infants had detectable IgG antibodies in their sera. It was demonstrated that the presence of HSV DNA in cord blood of newborns could be a risk marker for maternal-fetal transmission of the virus in asymptomatic pregnant women.

Human Bocavirus in Iranian children with acute gastroenteritis.

BACKGROUND: Human Bocavirus (HBoV) infection is of worldwide distribution. There is increasing evidencethat HBoV is pathogenic for the human gastroenteric tract. However, less data are available on the role of HBoVin gastroenteritis. The present study was aimed to determine the prevalence of HBoV in children with gastroenteritis. METHODS: Real-time PCR TaqMan was used to screen 200 stool specimens that had been referred to the virologylaboratory for HBoV evaluation. All of samples were collected on viral transport media. RESULTS: Of the 200 stool samples analyzed, 16 (8%) were positive for HBoV. Human Bocavirus positive samplesfrom patients aged between 1 to 5 years with acute gastroenteritis infection suggest a minor role of HBoVin gastroenteritis (p=0.0001). CONCLUSION: The study showed a high prevalence of human Bocavirus in young children with acute gastroenteritisdiseases in Iran, suggesting that HBoV play a role in the pathogenesis of gastroenteritis.

Merkel cell polyomavirus DNA in immunocompetent and immunocompromised patients with respiratory disease.

Merkel cell polyomavirus (MCPyV) was identified originally in association with a rare but aggressive skin cancer, Merkel cell carcinoma. The virus has since been found in the respiratory tract of some patients with respiratory disease. However, the role of MCPyV in the causation of respiratory disease has not been established. To determine the prevalence of MCPyV in 305 respiratory samples from immunocompetent and immunocompromised patients and evaluate their contribution to respiratory diseases, specimens were screened for MCPyV using single, multiplex, or real-time PCR; co-infection with other viruses was examined. Of the 305 samples tested, 10 (3.27%) were positive for MCPyV. The virus was found in two groups of patients: in 6 (2%) nasopharyngeal aspirate samples from children aged 26 days to 7 months who were immunocompetent; and in 4 (1.3%) of nasopharyngeal aspirate samples taken from patients aged 41 to 69 years who were severely immunosuppressed from leukemia or transplant therapy. Both groups had upper or lower respiratory tract infection. Co-infections with other viruses were found in 30% of the MCPyV positive samples. The data present a pattern of infection similar to that seen with the polyomaviruses JC and BK in which the virus is acquired during childhood, probably by the respiratory route. The viruses then establish latency and become reactivated in the event of immunosuppression.

Evidence of simian virus 40 infection in multiple organ transplant recipients with renal dysfunction.

Electron microscopy (EM), real-time polymerase chain reaction (PCR) and conventional PCR were used to identify viruses associated with infection in 2 transplantation patients. An autologous haematopoietic stem cell, liver and renal transplant recipient was found to be positive for simian virus 40 (SV40). Dual BK virus and SV40 infection was found in a heart and renal transplantation patient. SV40 infection can occur in immunocompromised patients.