The herpesviral Fc receptor fcr-1 down-regulates the NKG2D ligands MULT-1 and H60

Members of the α- and β-subfamily of herpesviridae encode glycoproteins that specifically bind to the Fc part of immunoglobulin (Ig)G. Plasma membrane resident herpesviral Fc receptors seem to prevent virus-specific IgG from activating antibody-dependent effector functions. We show that the mouse cytomegalovirus (MCMV) molecule fcr-1 promotes a rapid down-regulation of NKG2D ligands murine UL16-binding protein like transcript (MULT)-1 and H60 from the cell surface. Deletion of the m138/fcr-1 gene from the MCMV genome attenuates viral replication to natural killer (NK) cell response in an NKG2D-dependent manner in vivo. A distinct N-terminal module within the fcr-1 ectodomain in conjunction with the fcr-1 transmembrane domain was required to dispose MULT-1 to degradation in lysosomes. In contrast, down-modulation of H60 required the complete fcr-1 ectodomain, implying independent modes of fcr-1 interaction with the NKG2D ligands. The results establish a novel viral strategy for down-modulating NK cell responses and highlight the impressive diversity of Fc receptor functions

The First Evidence of Lyme Neuroborreliosis in Southern Bosnia and Herzegovina

Lyme borreliosis (LB) is caused by the spirochete Borrelia burgdorferi, which is transmitted to humans by ticks of the Ixodes ricinus complex. It is manifested by a variety of clinical symptoms and affects skin, joints, heart, and nervous system. Neurological manifestations are predictable and usually include meningoencephalitis, facial palsy, or radiculopathy. Recently, a dramatic rise in the number of diagnosed cases of LB has been observed on the global level. Here we show the first case of Lyme neuroborreliosis in southern Bosnia and Herzegovina, which was first presented by erythema chronicum migrans. Unfortunately, it was not recognized or well treated at the primary care medicine. After eight weeks, the patient experienced headache, right facial palsy, and lumbar radiculopathy. After the clinical examination, the neurologist suspected meningoencephalitis and the patient was directed to the Clinic for Infectious Disease of the University Hospital Mostar, where he was admitted. The successful antimicrobial treatment with the 21-day course of ceftriaxone was followed by normalization of neurological status, and then he was discharged from the hospital. This case report represents an alert to all physicians to be aware that LB is present in all parts of Bosnia and Herzegovina, as well as in the neighboring regions

Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia

We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=−0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=−0.258, t=−2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=−0.247, p=0.019) and antipsychotic treatment duration (ρ=−0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia

SARS-CoV-2 viral load in feces does not have a prognostic benefit in outcome of COVID-19: Clinical and immunological study

This study explores the correlation between immunological and clinical characteristics in coronavirus disease 2019 (COVID-19) patients with detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in feces, analyzing data from 251 patients admitted to Mostar University Clinical Hospital from December 2021 to January 2022. Methods involved reverse transcription quantitative polymerase chain reaction RT-qPCR from nasopharyngeal swabs and feces, alongside serological tests for anti-SARS-CoV-2 spike IgGs. Demographic and clinical data were collected through questionnaires and medical records. The data analyses were performed using SPSS statistical software. Death occurred in 53 patients (21.1%, P < 0.001), mostly in the elderly (47/53, 88.7%, P = 0.001) and immunocompromised (19/53, 35.8%, P = 0.05), particulary those developing acute respiratory insufficiency (ARI) (46/53, 86.8%, P = 0.004), and severe/critical disease (46/53, 86.8%, P = 0.002). Among the patients with positive anti-SARS-CoV-2 IgG antibodies (86/251, 34.3%, P < 0.001), 41 (47.7%) were vaccinated and 45 (52.3%) unvaccinated (P = 0.666), showing no significant differences in clinical outcomes or mortality. Unvaccinated patients with a negative antibody titer had a higher incidence of ARI (96/123, 78%, P = 0.029) and intensive care unit admission (22/123, 17.9%, P = 0.026), than those with a positive antibody titer. Forty-seven (62.7%) patients, out of the 75 hospitalized who provided a feces sample, were positive for SARS-CoV-2 RNA (P = 0.028), without statistical differences between fecal SARS-CoV-2 positive and negative groups regarding vaccination status (15/47, 31.9%, P = 0.493), antibody status (18/47, 38.3%, P = 0.628) or death outcome (5/47, 10.6%, P = 0.706). In conclusion, unvaccinated hospitalized patients with a severe COVID-19 presentation and a negative anti-spike SARS-CoV-2 IgG titer have more frequent adverse outcomes. This suggests cautious consideration for the diagnostic use of fecal samples compared to nasopharyngeal swabs

A Spread-Deficient Cytomegalovirus for Assessment of First-Target Cells in Vaccination▿ †

Human cytomegalovirus (HCMV) is a human pathogen that causes severe disease primarily in the immunocompromised or immunologically immature individual. To date, no vaccine is available. We describe use of a spread-deficient murine CMV (MCMV) as a novel approach for betaherpesvirus vaccination. To generate a spread-deficient MCMV, the conserved, essential gene M94 was deleted. Immunization with MCMV-ΔM94 is apathogenic and protective against wild-type challenge even in highly susceptible IFNαβR−/− mice. MCMV-ΔM94 was able to induce a robust CD4+ and CD8+ T-cell response as well as a neutralizing antibody response comparable to that induced by wild-type infection. Endothelial cells were identified as activators of CD8+ T cells in vivo. Thus, the vaccination with a spread-deficient betaherpesvirus is a safe and protective strategy and allows the linkage between cell tropism and immunogenicity. Furthermore, genomes of MCMV-ΔM94 were present in lungs 12 months after infection, revealing first-target cells as sites of genome maintenance

Vaccine hesitancy and refusal among parents: An international ID-IRI survey

Introduction: Although vaccines are the safest and most effective means to prevent and control infectious diseases, the increasing rate of vaccine hesitancy and refusal (VHR) has become a worldwide concern. We aimed to find opinions of parents on vaccinating their children and contribute to available literature in order to support the fight against vaccine refusal by investigating the reasons for VHR on a global scale. Methodology: In this international cross-sectional multicenter study conducted by the Infectious Diseases International Research Initiative (ID-IRI), a questionnaire consisting of 20 questions was used to determine parents' attitudes towards vaccination of their children. Results: Four thousand and twenty-nine (4,029) parents were included in the study and 2,863 (78.1%) were females. The overall VHR rate of the parents was found to be 13.7%. Nineteen-point three percent (19.3%) of the parents did not fully comply with the vaccination programs. The VHR rate was higher in high-income (HI) countries. Our study has shown that parents with disabled children and immunocompromised children, with low education levels, and those who use social media networks as sources of information for childhood immunizations had higher VHR rates (p &lt; 0.05 for all). Conclusions: Seemingly all factors leading to VHR are related to training of the community and the sources of training. Thus, it is necessary to develop strategies at a global level and provide reliable knowledge to combat VHR