High rates of hepatic involvement associated with new epidemic measles strains in Romania.

Similar to other European countries, a measles epidemic dominated by D8 genotype strains is ongoing since 2022 in our country. Recent reports of liver involvement associated with new measles virus (MeV) strains are scarce. The aim of the study was to compare the clinical characteristics between hospitalized patients with measles from the current epidemic and those from the previous outbreak and to analyze the risk factors associated with hepatic involvement. Data were collected retrospectively for all consecutive adult ( ≥18 years old) patients admitted between October 2022-April 2024 and January 2018-December 2019. A number of 228 patients from the current and 130 from the previous MeV epidemic were included. The main statistically significant differences were those regarding hepatic involvement (77.2% vs. 45.4%, p < 0.001) and significant hepatocellular injury (23.6% vs. 10.7%, p = 0.003). Compared to cases without liver involvement (123), patients with hepatocytolysis (235) had a higher prevalence of keratoconjunctivitis (42.5% vs. 28.4%, p = 0.01), thrombocytopenia (47.6% vs. 34.9%, p = 0.02), severe lymphopenia (51% vs. 35.7%, p = 0.007) and high fibrinogen levels (58.7% vs. 47.1%, p = 0.04). MeV strains from the 2022-2024 epidemic were the strongest predictors of hepatic involvement in the multivariable analysis (odds ratio = 4.3, 95% confidence interval: 2.5-7.4, p < 0.001). The mortality rate of patients with hepatocellular injury was 1.2%. The current measles epidemic is dominated by high rates of hepatic involvement compared to the previous outbreak. Although not associated with a significant mortality, the potential change in MeV hepatotropism could have important clinical implications and warrants further monitoring.

Immunological landscape of human lymphoid explants during measles virus infection.

In humans, lymph nodes are the primary site of measles virus (MeV) replication. To understand the immunological events that occur at this site, we infected human lymphoid tissue explants using a pathogenic strain of MeV that expresses GFP. We found that MeV infected 5%-15% of cells across donors. Using single-cell RNA-Seq and flow cytometry, we found that while most of the 29 cell populations identified in the lymphoid culture were susceptible to MeV, there was a broad preferential infection of B cells and reduced infection of T cells. Further subsetting of T cells revealed that this reduction may be driven by the decreased infection of naive T cells. Transcriptional changes in infected B cells were dominated by an interferon-stimulated gene (ISG) signature. To determine which of these ISGs were most substantial, we evaluated the proteome of MeV-infected Raji cells by mass spectrometry. We found that IFIT1, IFIT2, IFIT3, ISG15, CXCL10, MX2, and XAF1 proteins were the most highly induced and positively correlated with their expression in the transcriptome. These data provide insight into the immunological events that occur in lymph nodes during infection and may lead to the development of therapeutic interventions.

A novel approach for breast cancer treatment: the multifaceted antitumor effects of rMeV-Hu191.

BACKGROUND: The therapeutic potential of oncolytic measles virotherapy has been demonstrated across various malignancies. However, the effectiveness against human breast cancer (BC) and the underlying mechanisms of the recombinant measles virus vaccine strain Hu191 (rMeV-Hu191) remain unclear. METHODS: We utilized a range of methods, including cell viability assay, Western blot, flow cytometry, immunofluorescence, SA-ß-gal staining, reverse transcription quantitative real-time PCR, transcriptome sequencing, BC xenograft mouse models, and immunohistochemistry to evaluate the antitumor efficacy of rMeV-Hu191 against BC and elucidate the underlying mechanism. Additionally, we employed transcriptomics and gene set enrichment analysis to analyze the lipid metabolism status of BC cells following rMeV-Hu191 infection. RESULTS: Our study revealed the multifaceted antitumor effects of rMeV-Hu191 against BC. rMeV-Hu191 induced apoptosis, inhibited proliferation, and promoted senescence in BC cells. Furthermore, rMeV-Hu191 was associated with changes in oxidative stress and lipid homeostasis in infected BC cells. In vivo, studies using a BC xenograft mouse model confirmed a significant reduction in tumor growth following local injection of rMeV-Hu191. CONCLUSIONS: The findings highlight the potential of rMeV-Hu191 as a promising treatment for BC and provide valuable insights into the mechanisms underlying its oncolytic effect.

Multifaceted activation of STING axis upon Nipah and measles virus-induced syncytia formation.

Activation of the DNA-sensing STING axis by RNA viruses plays a role in antiviral response through mechanisms that remain poorly understood. Here, we show that the STING pathway regulates Nipah virus (NiV) replication in vivo in mice. Moreover, we demonstrate that following both NiV and measles virus (MeV) infection, IFNγ-inducible protein 16 (IFI16), an alternative DNA sensor in addition to cGAS, induces the activation of STING, leading to the phosphorylation of NF-κB p65 and the production of IFNß and interleukin 6. Finally, we found that paramyxovirus-induced syncytia formation is responsible for loss of mitochondrial membrane potential and leakage of mitochondrial DNA in the cytoplasm, the latter of which is further detected by both cGAS and IFI16. These results contribute to improve our understanding about NiV and MeV immunopathogenesis and provide potential paths for alternative therapeutic strategies.

Antiviral Properties of Moringa oleifera Leaf Extracts against Respiratory Viruses.

Moringa oleifera (M. oleifera) is a plant widely used for its beneficial properties both in medical and non-medical fields. Because they produce bioactive metabolites, plants are a major resource for drug discovery. In this study, two different cultivars of leaves of M. oleifera (Salento and Barletta) were obtained by maceration or microwave-assisted extraction (MAE). We demonstrated that extracts obtained by MAE exhibited a lower cytotoxic profile compared to those obtained by maceration at concentrations ranged from 25 to 400 µg/mL, on both Vero CCL-81 and Vero/SLAM cells. We examined their antiviral properties against two viruses, i.e., the human coronavirus 229E (HCoV-229E) and measles virus (MeV), which are both responsible for respiratory infections. The extracts were able to inhibit the infection of both viruses and strongly prevented their attack and entry into the cells in a range of concentrations from 50 to 12 µg/mL. Particularly active was the variety of Salento that registered a 50% inhibitory concentration (IC50) at 21 µg/mL for HCoV-229E and at 6 µg/mL for MeV. We identified the presence of several compounds through high performance liquid chromatography (HPLC); in particular, chlorogenic and neochlorogenic acids, quercetin 3-O-ß-d-glucopyranoside (QGP), and glucomoringin (GM) were mainly observed. In the end, M. oleifera can be considered a promising candidate for combating viral infections with a very strong action in the early stages of viral life cycle, probably by destructuring the viral particles blocking the virus-cell fusion.

Measles immunity status in Iranian infants and children and outbreak concerns: Time for reconsidering the vaccination schedule?

INTRODUCTION: Measles vaccination has greatly reduced the disease burden worldwide, but challenges remain due to variations in vaccine effectiveness across age groups. This study aimed to assess the serological profile of measles antibodies across different age groups, evaluate the impact of maternal immunity on antibody levels in infants under 12 months, and assess measles immunity in vaccinated individuals. MATERIAL AND METHODS: This cross-sectional study was conducted from June 2022 to January 2023 at the Children's Medical Center, a referral hospital in Iran. Serum samples were tested for measles-specific IgG and IgM antibodies using a commercial enzyme-linked immunosorbent assay (ELSA). An avidity assay was performed to assess measles virus-specific IgG antibodies on the samples that were positive and borderline for the measles IgG ELISA. RESULTS: The study included 969 participants across various age groups. Among them, 23% (221 out of 953) tested positive for measles IgM ELISA, and 52% (504 out of 969) for measles IgG ELISA. Regarding the avidity assay for measles virus-specific IgG, the majority (418 out of 573, 73%) showed high-avidity antibodies. Measles-specific IgG levels varied significantly across different age groups, with infants below 6 months old showing a mean IgG level of 477 mIU/mL, declining to 230 mIU/mL between 6 and 12 months, and increasing significantly to 683 mIU/mL in the 12 to 18 month age group, reaching a peak at 938 mIU/mL among children aged 18-72 months. CONCLUSION: The increasing IgM positivity among young Iranians suggests a rising risk of measles outbreaks, possibly due to vaccination gaps. Inadequate antibody levels in infants raise concerns about vaccination effectiveness. Considering declining maternal antibodies, vaccinating infants at 6-9 months could be beneficial. Boosters for adolescents and women may further mitigate outbreak risks.

Onward Virus Transmission after Measles Secondary Vaccination Failure.

Measles in persons with secondary vaccination failure (SVF) may be less infectious than cases in unvaccinated persons. Our systematic review aimed to assess transmission risk for measles after SVF. We searched PubMed, Embase, and Web of Science databases from their inception dates. Inclusion criteria were articles describing persons who were exposed to measles-infected persons who had experienced SVF. Across the included 14 studies, >3,030 persons were exposed to measles virus from SVF cases, of whom 180 were susceptible, indicating secondary attack rates of 0%-6.25%. We identified 109 cases of SVF from the studies; 10.09% (n = 11) of case-patients transmitted the virus, resulting in 23 further cases and yielding an effective reproduction number of 0.063 (95% CI 0.0-0.5). These findings suggest a remarkably low attack rate for SVF measles cases, suggesting that, In outbreak situations, public health management of unvaccinated persons could be prioritized over persons with SVF.

Host WD repeat-containing protein 5 inhibits protein kinase R-mediated integrated stress response during measles virus infection.

Some negative-sense RNA viruses, including measles virus (MeV), share the characteristic that during their infection cycle, cytoplasmic inclusion bodies (IBs) are formed where components of the viral replication machinery are concentrated. As a foci of viral replication, how IBs act to enhance the efficiency of infection by affecting virus-host interactions remains an important topic of investigation. We previously established that upon MeV infection, the epigenetic host protein, WD repeat-containing protein 5 (WDR5), translocates to cytoplasmic viral IBs and facilitates MeV replication. We now show that WDR5 is recruited to IBs by forming a complex with IB-associated MeV phosphoprotein via a conserved binding motif located on the surface of WDR5. Furthermore, we provide evidence that WDR5 promotes viral replication by suppressing a major innate immune response pathway, the double-stranded RNA-mediated activation of protein kinase R and integrated stress response. IMPORTANCE: MeV is a pathogen that remains a global concern, with an estimated 9 million measles cases and 128,000 measles deaths in 2022 according to the World Health Organization. A large population of the world still has inadequate access to the effective vaccine against the exceptionally transmissible MeV. Measles disease is characterized by a high morbidity in children and in immunocompromised individuals. An important area of research for negative-sense RNA viruses, including MeV, is the characterization of the complex interactome between virus and host occurring at cytoplasmic IBs where viral replication occurs. Despite the progress made in understanding IB structures, little is known regarding the virus-host interactions within IBs and the role of these interactions in promoting viral replication and antagonizing host innate immunity. Herein we provide evidence suggesting a model by which MeV IBs utilize the host protein WDR5 to suppress the protein kinase R-integrated stress response pathway.

Quantifying the long-term effects of measles infection-a retrospective cohort study.

OBJECTIVES: To assess whether measles infection has an impact on the rate of non-measles infectious diseases over an extended period. METHODS: This retrospective matched cohort study included 532 measles-diagnosed patients who were exactly matched with 2128 individuals without a previous measles diagnosis. Adjusted OR for any all-cause infectious diagnosis and any viral infection diagnosis ≤2 years after measles diagnosis between the measles and control groups was obtained from a conditional logistic regression model. The Cox proportional hazards model was used to estimate the hazard ratio. RESULTS: Previous measles virus (MeV) exposure was associated with an increased risk for all-cause non-measles infectious disease diagnosis (OR: 1.83, 95% CI: 1.26-2.64, p 0.001), with 492 diagnoses in the MeV-exposed group and 1868 diagnoses in the control group. Additionally, previous MeV exposure was linked to a higher risk of viral infection diagnosis (OR: 1.23, 95% CI: 1.01-1.59, p < 0.05), with 302 viral infection diagnoses in the MeV-exposed group and 1107 diagnoses in the control group. The hazard ratio for viral diagnosis in the MeV-exposed group compared with the control group was 1.54 (95% CI: 1.18-2.02, p < 0.001). DISCUSSION: Individuals diagnosed with measles had a moderately increased risk of being diagnosed with all-cause non-measles infectious disease or viral infection. This observational individual-level study supports previous ecological and individual population-level studies.

Immunogenicity of a peptide-based vaccine for measles: a pilot evaluation in a mouse model.

Although neutralizing antibody is an established correlate of protection for measles, T cell-mediated responses play at least two critical roles in immunity to measles: first, through provision of 'help' enabling robust humoral immune responses; and second, through clearance of measles virus-infected cells. Previously, we identified 13 measles-derived peptides that bound to human leukocyte antigen (HLA) molecules in Priess cells infected with measles virus. In this study, we evaluated the immunogenicity of these peptides in a transgenic mouse model. Our results demonstrated that these peptides induced Th1-biased immune responses at varying levels. Of the 13 peptides, the top four immunogenic peptides were further selected for a viral challenge study in mice. A vaccine based on a combination of these four peptides reduced morbidity and weight loss after viral challenge compared to placebo. Our results emphasize the potential of T cell-mediated, peptide-based vaccines against measles.

Onward transmission of measles virus among vaccinated cases in a large community outbreak in Auckland, New Zealand, 2019.

BACKGROUND: Isolation of cases and quarantining of non-immune contacts are the mainstay of measles outbreak management in elimination settings. Serology testing of exposed contacts may not be feasible in large outbreaks; therefore, vaccination history is used as a proxy for determining immunity to measles and thus prevention of onward virus transmission. This study sought to investigate the risk of measles virus transmission from individuals with a history of one or two doses of measles-containing vaccine (MCV). METHODS:  Retrospective analysis of data from measles cases reported to Auckland Regional Public Health Service during the 2019 Auckland region measles outbreak. Vaccination history was verified using patient records and the New Zealand National Immunisation Register. Onward transmission was determined through case interviews and assessment of exposed contacts. RESULTS:  1451 measles cases were assessed as eligible for vaccination at the time of measles outbreak. Of these, 1015 (70.0%) were unvaccinated, 220 (15.2%) had unknown vaccination status, 139 (9.6%) had received only one dose of MCV and 77 (5.3%) had received two doses of the vaccine. Compared to unvaccinated cases, the odds of onward transmission were lower among those with one dose only (OR 0.41, 95% CI: 0.20-0.75) or two doses of MCV (OR 0.44, 95% CI: 0.17-0.95). Median time since vaccination was longer among those with onward transmission compared to those without onward transmission for one and two doses of the vaccine, suggesting a potential effect of waning immunity among this cohort. CONCLUSION:  These findings support the hypothesis that measles cases with a history of prior vaccination are less likely to transmit the virus to others compared to unvaccinated cases. Such information can be used to support decisions around quarantine requirements for vaccinated contacts in future measles outbreaks.

Measles in the vaccinated host.

A woman in her 40s known to have systemic lupus erythematosus presented with a maculopapular rash on her face, neck and chest following measles exposure. She had received a single-dose measles vaccine as a child in the 1970s and was therefore presumed to be immune, and thus not infectious. As a result, she was initially managed in an open bay. Measles virus IgM antibody in serum was undetectable; however, measles virus RNA was subsequently detected in throat swab by PCR, which is consistent with current infection. Measles is one of the most transmissible diseases in the world and cases are rising both in the UK and globally. Our case and literature review highlight the risk of vaccine failure in measles, especially in people who have not received two doses of the measles, mumps and rubella vaccine. It also highlights the challenges in diagnosing measles in previously vaccinated individuals.

Immunity Against Measles in Korean Autologous Hematopoietic Stem Cell Transplant Recipients.

The seropositivity of measles antibodies among 261 autologous stem cell transplant recipients (ASCTs) in Korea, assessed approximately 1-2 years after transplant (median, 11 months; interquartile range, 9-14), was significantly lower than age- and sex-matched control healthcare workers (83.1% [217/261] vs. 90.3% [539/597], P = 0.002). The findings underscore the vulnerability of adult ASCT recipients to measles. Clinicians should prioritize testing for measles IgG after ASCT and consider vaccination for ASCT recipients who remain seronegative 2 years after ASCT.

What's going on with measles?

Measles is a highly transmissible systemic viral infection associated with substantial mortality primarily due to secondary infections. Measles induces lifelong immunity to reinfection but loss of immunity to other pathogens. An attenuated live virus vaccine is highly effective, but lapses in delivery have resulted in increasing cases worldwide. Although the primary cause of failure to control measles is failure to vaccinate, waning vaccine-induced immunity and the possible emergence of more virulent virus strains may also contribute.

Evaluation of the sensitivity of a measles diagnostic real-time RT-PCR assay incorporating recently observed priming mismatch variants, 2024.

We investigated a variant of measles virus that encodes three mismatches to the reverse priming site for a widely used diagnostic real-time RT-PCR assay; reduction of sensitivity was hypothesised. We examined performance of the assay in context of the variant using in silico data, synthetic RNA templates and clinical specimens. Sensitivity was reduced observed at low copy numbers for templates encoding the variant sequence. We designed and tested an alternate priming strategy, rescuing the sensitivity of the assay.

Measles outbreak in 2019: a warning for the post-COVID-19 pandemic period.

Introduction. At the end of 2019 and the year before, there was a significant spread of measles in the World Health Organization (WHO) European Region.Gap statement. Among the countries that reported, a measles outbreak was Bosnia and Herzegovina (BiH).Aim. To describe the measles outbreak in BiH (an entity of the Federation of BiH, FBiH) in 2019.Methodology. Confirmatory IgM serology, measles nucleic acid detection by real-time RT-PCR and virus genotyping were done in the WHO-accredited laboratory for measles and rubella at the Clinical Center of the University of Sarajevo, Unit for Clinical Microbiology. Genotype was determined in all measles-RNA-positive cases by sequence analysis of the 450 nt fragment coding the C-terminal of measles virus nucleoprotein (N).Results. From 1 January to 31 December 2019, 1332 measles cases were reported, with the peak observed in April 2019 (413/1332, 31.01 %). Sarajevo Canton had the highest incidence, number of cases and percentage (206.4; 868/1332; 65.17 %) of measles cases. Around four-fifths of infected persons were unvaccinated (1086/1332, 81.53 %), while 4.58 % of the patients (61/1332) were immunized with one dose of measles-containing vaccine. The highest proportion of cases was found in children 0-6 years of age (738/1332, 55.41 %). Measles IgM positivity was determined in 75.88 % (346/456), while virus RNA was detected in 82.46 % (47/57) of the swab samples. All measles virus sequences belonged to genotype B3. SNP (position 216: C=>T) was detected in 1 of the 40 sequences obtained during this outbreak.Conclusion. Due to suboptimal immunization coverage, BiH belongs to countries at a high risk for measles outbreaks. Post-COVID-19 (coronavirus disease 2019) pandemic, targeted and tailored strategies are required to ensure routine vaccination demand and acceptance and broad partner and stakeholder group participation.

Three SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective.

As the new SARS-CoV-2 Omicron variants and subvariants emerge, there is an urgency to develop intranasal, broadly protective vaccines. Here, we developed highly efficacious, intranasal trivalent SARS-CoV-2 vaccine candidates (TVC) based on three components of the MMR vaccine: measles virus (MeV), mumps virus (MuV) Jeryl Lynn (JL1) strain, and MuV JL2 strain. Specifically, MeV, MuV-JL1, and MuV-JL2 vaccine strains, each expressing prefusion spike (preS-6P) from a different variant of concern (VoC), were combined to generate TVCs. Intranasal immunization of IFNAR1-/- mice and female hamsters with TVCs generated high levels of S-specific serum IgG antibodies, broad neutralizing antibodies, and mucosal IgA antibodies as well as tissue-resident memory T cells in the lungs. The immunized female hamsters were protected from challenge with SARS-CoV-2 original WA1, B.1.617.2, and B.1.1.529 strains. The preexisting MeV and MuV immunity does not significantly interfere with the efficacy of TVC. Thus, the trivalent platform is a promising next-generation SARS-CoV-2 vaccine candidate.

Co-delivery of oncolytic virus and chemotherapeutic modality: Vincristine against prostate cancer treatment: A potent viro-chemotherapeutic approach.

Prostate cancer is a prevalent carcinoma among males, and conventional treatment options are often limited. Cytotoxic chemotherapy, despite its drawbacks, remains a mainstay. We propose a targeted co-delivery approach using nanoscale delivery units for Oncolytic measles virus (OMV) and vincristine (VC) to enhance treatment efficacy. The HA-coated OMV + VC-loaded TCs nanoformulation is designed for targeted oncolytic activity in prostate cancer. The CD44 expression analysis in prostate cancer cell lines indicates a significantly high expression in PC3 cells. The optimization of nanoformulations using Design of Expert (DOE) is performed, and the preparation and characterization of HA-coated OMV + VC-loaded TCs nanoformulations are detailed showing average particle size 397.2 ± 0.01 nm and polydispersity index 0.122 with zeta potential 19.7 + 0.01 mV. Results demonstrate successful encapsulation efficiency with 2.4 × 106 TCID50/Ml and sustained release of OMV and VC from the nanoformulation for up to 72 h. In vitro, assays reveal potent anticancer activity at 10 ± 0.71% cell viability in PC3 cells compared to 73 ± 0.66% in HPrEC and significant morphological changes at 90 µg/ml in dose and time-dependent manner. The co-formulation showed positive cell death 49.5 ± 0.02% at 50 µg PI/ml in PBS and 54.3% cell cycle arrest at the G2/M phase, 8.1% G0/G1 and 5.7% at S phase, with significant mitochondrial membrane potential (MMP) at 50 µg/ml, as assessed by flow cytometry (FACS). The surface-integrating ligand approach enhances the targeted delivery of the oncolytic virus and chemotherapeutic drug, presenting a potential alternative for prostate cancer treatment and suggested that co-administering VC and OMV in a nanoformulation could improve therapeutic outcomes while reducing chemotherapeutic drug doses.