Virus Infection Research Articles

Hematological Cancer and Viral Infection

Hematological cancer patients are particularly vulnerable to the morbidity and death caused by viral infections. But, it is not well known how common viral infections are or what effects they have on patients undergoing traditional nontransplant treatment. How severe and how long T-cell-mediated immune suppression is determines the variation in viral infection incidence and prognosis between patient groups. Topics covered in this mini-review article include late CMV infection, new viral pathogens (human herpesvirus-6, BK virus, adenovirus, and human metapneumovirus), advancements in molecular diagnostics, and the possibility of novel agents for viral prophylaxis (maribavir) or preemptive therapy (valganciclovir). The infections caused by these viruses have been extensively studied. If we want to understand the range of these viral diseases and come up with effective ways to prevent and cure them, we need well-designed prospective trials. Patients undergoing nontransplant treatment for hematological malignancies are at greater risk for viral infections; this is especially important given the rising use of drugs like alemtuzumab, which cause significant T-cell depletion.

Multiple functions of the herpesvirus UL14 gene product in viral infection.

Herpesviruses are a family of double-stranded DNA viruses with a tegument structure and a genome composed of a single sequence and terminal repeat (TR) sequences. The herpesvirus UL14 gene encodes the protein UL14 (pUL14), which has various subcellular localizations and plays a vital role in regulating immediate-early (IE) gene transcription and expression, influences the intracellular localization patterns of several proteins belonging to the capsid and the DNA packaging machinery, participates in secondary envelopment, and influences viral particle release. Additionally, pUL14 has roles in maintaining cellular homeostasis and preventing apoptosis. This review discusses how pUL14 engages in the life cycle of herpesviruses and provides new ideas for further research on pUL14's function in viral infection.

Insight into structural properties of viral G protein-coupled receptors and their role in the viral infection: IUPHAR Review 41.

G protein-coupled receptors (GPCRs) are pivotal in cellular signalling and drug targeting. Herpesviruses encode GPCRs (vGPCRs) to manipulate cellular signalling, thereby regulating various aspects of the virus life cycle, such as viral spreading and immune evasion.vGPCRs mimic host chemokine receptors, often with broader signalling and high constitutive activity. This review focuses on the recent advancements in structural knowledge about vGPCRs, with an emphasis on molecular mechanisms of action and ligand binding. The structures of US27 and US28 from human cytomegalovirus (HCMV) are compared to their closest human homologue, CX3CR1. Contrasting US27 and US28, the homotrimeric UL78 structure (HCMV) reveals more distance to chemokine receptors. Open reading frame 74 (ORF74; Kaposi's sarcoma-associated herpesvirus) is compared to CXCRs, whereas BILF1 (Epstein-Barr virus) is discussed as a putative lipid receptor. Furthermore, the rolesof vGPCRs in latency and lytic replication, reactivation, dissemination and immune evasion arereviewed, together with their potential as drug targets for virus infections and virus-related diseases.

Tight junction protein LSR is a host defense factor against SARS-CoV-2 infection in the small intestine.

The identification of host factors with antiviral potential is important for developing effective prevention and therapeutic strategies against SARS-CoV-2 infection. Here, by using immortalized cell lines, intestinal organoids, ex vivo intestinal tissues and humanized ACE2 mouse model as proof-of-principle systems, we have identified lipolysis-stimulated lipoprotein receptor (LSR) as a crucial host defense factor against SARS-CoV-2 infection in the small intestine. Loss of endogenous LSR enhances ACE2-dependent infection by SARS-CoV-2 Spike (S) protein-pseudotyped virus and authentic SARS-CoV-2 virus, and exogenous administration of LSR protects against viral infection. Mechanistically, LSR interacts with ACE2 both in cis and in trans, preventing its binding to S protein, and thus inhibiting viral entry and S protein-mediated cell-cell fusion. Finally, a small LSR-derived peptide blocks S protein binding to the ACE2 receptor in vitro. These results identify both a previously unknown function for LSR in antiviral host defense against SARS-CoV-2, with potential implications for peptide-based pan-variant therapeutic interventions.

In Silico Design of a Solution-Gated Graphene Transistor Sensor for the Efficient Detection of Guanine Quadruplexes.

Guanine quadruplexes (G4s) are nucleic acid structures present in diverse regions of the genome, such as telomeres and transcription initiators. Recently, the different biological roles of G4s have been evidenced as well as their role as biomarkers for tumors or viral infections. However, the fast and efficient detection of G4s in complex matrices remains elusive. In this contribution, by using long-scale molecular dynamics simulations, we propose the design of a biosensor based on organic field-effect transistors recognizing G4s. In particular, we show that the interaction of the G4s with the biosensor is translated into a change in the charge density profile, which correlates with the electrical transduction of the signal, thus allowing the detection of the nucleic acid structure. We also provide rules of thumb for the optimization of the design of the device and more generally for the integration of computationally driven design approaches.

The deficient CLEC5A ameliorates the behavioral and pathological deficits via the microglial Aβ clearance in Alzheimer’s disease mouse model

BackgroundAlzheimer’s disease (AD) is a neurodegenerative disease that causes cognitive dysfunction in older adults. One of the AD pathological factors, β-Amyloid (Aβ), triggers inflammatory responses and phagocytosis of microglia. C-type lectin domain family 5 member A (CLEC5A) induces over-reactive inflammatory responses in several virus infections. Yet, the role of CLEC5A in AD progression remains unknown. This study aimed to elucidate the contribution of CLEC5A to Aβ-induced microglial activation and behavioral deficits.MethodsThe AD mouse model was crossed with Clec5a knockout mice for subsequent behavioral and pathological tests. The memory deficit was revealed by the Morris water maze, while the nociception abnormalities were examined by the von Frey filament and hotplate test. The Aβ deposition and microglia recruitment were identified by ELISA and immunohistochemistry. The inflammatory signals were identified by ELISA and western blotting. In the Clec5a knockdown microglial cell model and Clec5a knockout primary microglia, the microglial phagocytosis was revealed using the fluorescent-labeled Aβ.ResultsThe AD mice with Clec5a knockout improved Aβ-induced memory deficit and abnormal nociception. These mice have reduced Aβ deposition and increased microglia coverage surrounding the amyloid plaque, suggesting the involvement of CLEC5A in AD progression and Aβ clearance. Moreover, the phagocytosis was also increased in the Aβ-stressed Clec5a knockdown microglial cell lines and Clec5a knockout primary microglia.ConclusionThe Clec5a knockout ameliorates AD-like deficits by modulating microglial Aβ clearance. This study implies that targeting microglial Clec5a could offer a promising approach to mitigate AD progression.

Enhanced Recovery and Detection of Highly Infectious Animal Disease Viruses by Virus Capture Using Nanotrap® Microbiome A Particles

This study reports the use of Nanotrap® Microbiome A Particles (NMAPs) to capture and concentrate viruses from diluted suspensions to improve their recovery and sensitivity to detection by real-time PCR/RT-PCR (qPCR/RT-qPCR). Five highly infectious animal disease viruses including goatpox virus (GTPV), sheeppox virus (SPPV), lumpy skin disease virus (LSDV), peste des petits ruminants virus (PPRV), and African swine fever virus (ASFV) were used in this study. After capture, the viruses remained viable and recoverable by virus isolation (VI) using susceptible cell lines. To assess efficacy of recovery, the viruses were serially diluted in phosphate-buffered saline (PBS) or Eagle’s Minimum Essential Medium (EMEM) and then subjected to virus capture using NMAPs. The NMAPs and the captured viruses were clarified on a magnetic stand, reconstituted in PBS or EMEM, and analyzed separately by VI and virusspecific qPCR/RT-qPCR. The PCR results showed up to a 100-fold increase in the sensitivity of detection of the viruses following virus capture compared to the untreated viruses from the same dilutions. Experimental and clinical samples were subjected to virus capture using NMAPs and analyzed by PCR to determine diagnostic sensitivity (DSe) that was comparable (100%) to that determined using untreated (-NMAPs) samples. NMAPs were also used to capture spiked viruses from EDTA whole blood (EWB). Virus capture from EWB was partially blocked, most likely by hemoglobin (HMB), which also binds NMAPs and outcompetes the viruses. The effect of HMB could be removed by either dilution (in PBS) or using HemogloBind™ (Biotech Support Group; Monmouth Junction, NJ), which specifically binds and precipitates HMB. Enhanced recovery and detection of viruses using NMAPs can be applicable to other highly pathogenic animal viruses of agricultural importance.

Manifestation of selection traits and properties of forage productivity in groups of alfalfa varieties with different resistance to viral and phytoplasma infections

The research was conducted in 2019–2023 in Belgorod region with the purpose of breeding evaluation of alfalfa cultivars with different resistance to «witches’ broom alfalfa» (WBA). Fifty-two selection samples belonging to species Medicago sativa L., M. varia Mart., M. falcata L. The soil is typical chernozem, humus content (according to Tyurin) 4.7…5.0 %, The year of sowing – 2019. Predecessor – pure fallow. Plots – two-row long 3.5 m, row spacing width – 0.3 m. Repetition – five times. Standard – variety Belgorodskaya 86, sown through 5 numbers. Seeding rate of 100 germinated seeds per 1 linear meter. It was found that the group of varietal samples (n = 10) with low resistance to WBA (variation of prevalence 24.3–34.9 %) is characterized by a greater accumulation of protein (by 44.6 g/kg, t = 8.0, p 0.05), higher foliage (by 4.8 %, t = 3.7, p 0.05) and height (by 25.3 cm, t = 6.2, p 0.05), compared to the group of varieties resistant to WBA (n = 12) (prevalence variation 4.6… 9.1 %). Varieties with high resistance to WBA, belong to yellow and yellow-hybrid alfalfa varieties: Pavlovskaya 7, PO-172, Marusinskaya 425, PO-173, Sarga, PO-174, Victoria, 20–89 H, 193–95d, PO-175, SGPR-8, Vela×Sarga. Varieties with low resistance to VML belong to blue alfalfa and partially – blue-hybrid varieties: Krasnoyaruzhskaya 2, SI-139, SI-138, Plateau, Verko, Luzelle, Salsa, Kreno, Galaxi, Planet.

Health Facility Capacity and Health-care Worker Knowledge, Attitudes, and Practices of Hepatitis B Vaccine Birth-dose and Maternal Tetanus-Diphtheria Vaccine Administration in Nigeria: A Baseline Assessment.

Hepatitis B virus (HBV) and neonatal tetanus infections remain endemic in Nigeria despite the availability of safe, effective vaccines. We aimed to determine health facilities' capacity for hepatitis B vaccine birth dose (HepB-BD) and maternal tetanus-diphtheria (Td) vaccination and to assess knowledge, attitudes, and practices of HepB-BD and maternal Td vaccine administration among health facility staff in Nigeria. This was a cross-sectional study assessing public primary and secondary health facilities in Adamawa and Enugu States. A multistage sampling approach was used to select 40 facilities and 79 health-care workers (HCWs) from each state. A structured facility assessment tool and standardized questionnaire evaluated facility characteristics and HCW knowledge, attitudes, and practices related to HepB-BD and maternal Td vaccination. Frequencies and proportions were reported as descriptive statistics. The survey of 80 facilities revealed that 73.8% implemented HepB-BD and maternal Td vaccination policies. HepB-BD was administered within 24 h of birth at 61.3% of facilities and at all times at 57.5%. However, administration seldom occurred in labor and delivery (35%) or maternity wards (16.3%). Nearly half of the facilities (46.3%) had HCWs believing there were contraindications to HepB-BD vaccination. Among 158 HCWs, 26.5% believed tetanus could be transmitted through unprotected sex, prevented by vaccination at birth (46.1%), or by avoiding sharing food and utensils. 65% of HCWs knew HBV infection had the worst outcome for newborns. The limited implementation of national policies on HepB-BD and maternal Td vaccination, coupled with knowledge gaps among HCWs, pose significant challenges to timely vaccination, necessitating interventions to address these gaps.

Loss to follow-up of patients after antiviral treatment as an additional barrier to HCV elimination

BackgroundEliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it.MethodsPatients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study.ResultsIn the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy.ConclusionsIn a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy.

DENV and ZIKV infection: Species specificity and broad cell tropism

Nearly one-third of countries worldwide have reported cases of Dengue virus (DENV) and Zika virus (ZIKV) infections, highlighting the significant threat these viruses pose to global public health. As members of the Flavivirus genus within the Flaviviridae family, DENV and ZIKV have demonstrated the ability to infect a wide range of cell lines from multiple species in vitro. However, the range of susceptible animal models is notably limited, and field studies indicate that their capacity to infect host organisms is highly restricted, with a very narrow range of target cells in vivo. The virus's ability to hijack host cellular machinery plays a crucial role in determining its cellular and species specificity. In this review, we examine how DENV and ZIKV exploit host cells to facilitate their replication, offering new insights that could inform the development of antiviral drugs and therapeutic targets.

Construction and Evaluation of a Model for the Prediction of Risk Factors Associated with Severe Pneumonia in Patients with Positive Hepatitis B Core Antibody and COVID-19 Infection in China

Background: Hepatitis B virus (HBV) infection is a high-risk factor for severe COVID-19 cases, leading clinicians to enhance the monitoring of patients with concurrent HBV and COVID-19 infections. However, this focus is typically on patients with active HBV infection. Patients who are HBV surface antigen (HBsAg) negative and HBV core antibody (anti-HBc) positive are often considered to have either a past infection that has naturally cleared or to be in a low-replication state, and thus receive less clinical attention. However, in immunosuppressed states, such as during immunosuppressive treatment following COVID-19 infection, the virus in these patients may reactivate. In such cases, this reactivation can increase the risk of COVID-19 progressing to a severe illness. Therefore, being HBsAg negative and anti-HBc positive could be a potential risk factor for severe COVID-19. Studying the combination of anti-HBc positivity and COVID-19 infection can help identify high-risk populations, allowing for the implementation of targeted prevention and management measures, thereby reducing the occurrence of severe COVID-19 cases. Objectives: To establish and evaluate a model for predicting severe pneumonia in patients with positive anti-HBc combined with COVID-19 infection. Methods: We retrospectively enrolled 380 patients who tested positive for anti-HBc, negative for HBsAg, and HBV e-antigen (HBeAg), combined with COVID-19 infection, in our hospital from December 2022 to May 2023. Based on the inclusion criteria, 163 patients were included in the study. We applied the Lasso binary logistic regression model to optimize feature selection, identifying eight non-zero coefficients using a minimum of one standard error. Using the multiple logistic regression method with backward selection, we screened six factors from the eight selected by the Lasso binary logistic regression model. These six factors were used to construct the predictive model and a nomogram. The validity of our nomogram was assessed using the area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow (HL) test, and decision-curve analysis (DCA). Results: Hypertension, diabetes, decreased absolute lymphocyte count, prolonged prothrombin time, elevated aspartate aminotransferase, and decreased albumin are high-risk factors for severe pneumonia in patients with positive anti-HBc combined with COVID-19 infection. The AUC of the predictive model constructed using these six factors is 0.785, with a 95% confidence interval of (0.709-0.862). The HL test, performed using the calibration curve, yielded a p-value of 0.868. The application of this diagnostic curve will increase the net benefit when the threshold probability is between 5% and 75%. Conclusions: The constructed nomogram can be used to predict the risk of patients with positive anti-HBc combined with COVID-19 infection progressing to severe pneumonia, based on routine blood parameters, liver function, coagulation, lactate dehydrogenase levels, and the patient's underlying disease. The predictive model demonstrates good discrimination, calibration, and clinical utility.

Prevalence of JC polyomavirus among rheumatoid arthritis and systemic lupus erythematosus patients and its correlation with vitamin D levels

Background and Objectives: Vitamin D deficiency in viral infection associated with autoimmune diseases is well docu- mented. This study assessed the prevalence of JC virus in patients with rheumatoid arthritis (RA) and systemic lupus erythe- matosus (SLE), and its correlation with vitamin D level. Materials and Methods: Serum and urine samples were collected from 50 patients with RA and SLE. DNA was extracted and subjected to PCR test. Positive PCR products were sequenced, phylogenetic tree was constructed to determine the JC virus genotype. The patient’s vitamin D level was evaluated. Results: Of 50 patients, 19 (38%) were diagnosed as RA, and 31 (62%) were identified as SLE. JC virus DNA was detected in 17 (34%) patients’ urine samples including 5 (26.3%) RA and 12 (38.7%) SLE cases. JC virus DNA was detected 2 (4%) in patients’ serum samples (one RA. and one SLE). JC virus genotype 3A was dominant. Interestingly, the SLE patients with positive JC virus showed lowered vitamin D compared to patients with negative JC virus (P&lt;0.005). Conclusion: Given the high rate of JC virus, DNA detection and susceptibility of patients for PML development, it is rec- ommended that detection of JC virus DNA and vitamin D level should be implemented for patients with RA/SLE prior to treatment.

Design and Test of Molecules that Interfere with the Recognition Mechanisms between the SARS-CoV-2 Spike Protein and Its Host Cell Receptors.

The disruptive impact of the COVID-19 pandemic has led the scientific community to undertake an unprecedented effort to characterize viral infection mechanisms. Among these, interactions between the viral glycosylated Spike and the human receptors ACE2 and TMPRSS2 are key to allowing virus invasion. Here, we report and test a fully rational methodology to design molecules that are capable of perturbing the interactions between these critical players in SARS-CoV-2 pathogenicity. To this end, we computationally identify substructures on the fully glycosylated Spike protein that are not intramolecularly optimized and are thus prone to being stabilized by forming complexes with ACE2 and TMPRSS2. With the aim of competing with the Spike-mediated cell entry mechanisms, we have engineered the predicted putative interaction regions in the form of peptide mimics that could compete with Spike for interaction with ACE2 and/or TMPRSS2. Experimental models of viral entry demonstrate that the designed molecules are able to interfere with viral entry into ACE2/TMPRSS2 expressing cells, while they have no effects on the entry of control viral particles that do not harbor the Spike protein or on the entry of Spike-presenting viral particles into cells that do not display its receptors on their surface.

Combination of proviral and antiviral roles of B cell-intrinsic STAT1 expression defines parameters of chronic gammaherpesvirus infection.

Gammaherpesviruses are species-specific, ubiquitous pathogens that establish lifelong infection in their hosts and are associated with cancers, including B cell lymphomas. Type I and II interferons (IFNs) are critical for the control of acute and chronic gammaherpesvirus infection. However, the cell type-specific role of IFN signaling during natural infection is poorly defined and is masked by the altered viral pathogenesis observed in hosts with global IFN deficiencies. STAT1 is a constitutively expressed transcription factor that is critical for the effector function of type I and II IFNs. In this study, we defined the impact of B cell-specific STAT1 expression on gammaherpesvirus infection using murine gammaherpesvirus 68 (MHV68). While the acute stage of MHV68 infection was not affected, we found opposite, anatomic site-dependent effects of B cell-intrinsic STAT1 expression during chronic infection. Consistent with the antiviral role of STAT1, B cell-specific STAT1 expression attenuated the latent viral reservoir in peritoneal B cells of chronically infected mice. In contrast, STAT1 expression in splenic B cells supported the establishment of the latent MHV68 reservoir in germinal center B cells, revealing an unexpected proviral role of B cell-intrinsic STAT1 expression during chronic gammaherpesvirus infection. These STAT1-dependent MHV68 chronic infection phenotypes were fully recapitulated in the peritoneal cavity but not the spleen of mice with B cell-specific deficiency of type I IFN receptor. In summary, our study uncovers the intriguing combination of proviral and antiviral roles of B cell-intrinsic STAT1 expression during chronic gammaherpesvirus infection.IMPORTANCEInterferons (IFNs) execute broadly antiviral roles during acute and chronic viral infections. The constitutively expressed transcription factor STAT1 is a critical downstream effector of IFN signaling. Our studies demonstrate that B cell-intrinsic STAT1 expression has opposing and anatomic site-dependent roles during chronic gammaherpesvirus infection. Specifically, B cell-intrinsic STAT1 expression restricted gammaherpesvirus latent reservoir in the peritoneal cavity, consistent with the classical antiviral role of STAT1. In contrast, decreased STAT1 expression in splenic B cells led to the attenuated establishment of gammaherpesvirus latency and decreased latent infection of germinal center B cells, highlighting a novel proviral role of B cell-intrinsic STAT1 expression during chronic infection with a B cell-tropic gammaherpesvirus. Interestingly, B cell-specific type I IFN receptor deficiency primarily recapitulated the antiviral role of B cell-intrinsic STAT1 expression, suggesting the compensatory function of B cell-intrinsic type II IFN signaling or an IFN-independent proviral role of B cell-intrinsic STAT1 expression during chronic gammaherpesvirus infection.

Undergraduate health science students' knowledge, attitudes, and practices about hepatitis B virus infection prevention at Addis Ababa university, Ethiopia: a cross-sectional study

Background: Hepatitis B (HB) is a serious liver-damaging infection that is caused by the HB virus (HBV). Healthcare professionals are especially susceptible to HB, a serious global public health concern. The aim of this study was to assess the undergraduate health science students’ knowledge, attitudes, and practices regarding the prevention of HBV infection. Methods: A cross-sectional study was conducted among third- and fourth-year health science students at the college of health sciences (CHS), Addis Ababa university (AAU) in Ethiopia. Self-administered structured questionnaire was used to collect the data. Chi square was used to examine the relationship between the outcome variables (mean knowledge, attitude, and practice) and a few socio-demographic factors (age, sex, and year of study). Statistical significance will be determined by p values less than 0.05. Results: Half of the study participants had adequate knowledge about the HBV. More than half (55%) of research participants were in favor of the HBV vaccination. The Chi square test was used to look at the association between the participants' mean knowledge score and specific socio-demographic characteristics. However, no significant association has been found with any of the selected socio-demographic variables. Conclusions: While undergraduate health science students generally demonstrate an acceptable level of knowledge and positive attitudes toward HBV infection prevention, there remain significant gaps in practice, particularly regarding vaccination uptake and adherence to standard precautions.

SARS-CoV-2 XBB.1.5 mRNA booster vaccination elicits limited mucosal immunity.

Current COVID-19 vaccines provide robust protection against severe disease but minimal protection against acquisition of infection. Intramuscularly administered COVID-19 vaccines induce robust serum neutralizing antibodies (NAbs), but their ability to boost mucosal immune responses remains to be determined. In this study, we show that the XBB.1.5 messenger RNA (mRNA) boosters result in increased serum neutralization to multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in humans, including the dominant circulating variant JN.1. In contrast, we found that the XBB.1.5 mRNA booster did not augment mucosal NAbs or mucosal IgA responses, although acute SARS-CoV-2 XBB infection substantially increased mucosal antibody responses. These data demonstrate that current XBB.1.5 mRNA boosters substantially enhance peripheral antibody responses but do not robustly increase mucosal antibody responses. Our data highlight a separation between the peripheral and mucosal immune systems in humans and emphasize the importance of developing next-generation vaccines to augment mucosal immunity to protect against respiratory virus infections.

The heterologous expression of novel recombinant protein composed of HN and F moieties of Newcastle disease virus and immunogenicity evaluation in mouse model

Background and Objectives: The rapid spread of Newcastle disease (ND), driven by extensive commercial exchange in the poultry industry, necessitates urgent preventive measures. Although effective vaccines against the Newcastle disease virus (NDV) have been used since 1940, recent outbreaks and the limitations of current vaccines highlight the need for improved solutions. Advances in synthetic biology, reverse vaccinology, molecular biology, and recombinant DNA technology over the past 20 years have led to the development of recombinant vaccines, which offer enhanced protection and broader immuno- genic coverage against NDV. This study aimed to express the immunogenic domains of Hemagglutinin Neuraminidase (HN) and Fusion (F) glycoproteins, linked to the heat-labile enterotoxin B subunit (LTB) bio-adjuvant, to develop an effective and reliable recombinant vaccine for NDV. Materials and Methods: In this study, the L(HN)2F protein, composed of the LTB bio-adjuvant and the immunogenic regions of the doubled Hemagglutinin Neuraminidase (HN-HN) and Fusion (F) epitope, was expressed in Escherichia coli. Subcutaneous injection was used to evaluate the humoral immune response in mice and the result was compared with B1 vaccine. Results: The induction of strong humoral immune responses proved the strong immunoreactivity of the recombinant protein. Conclusion: The IgG elicited by the recombinant proteins was comparable to that of the commercial B1 vaccine against NDV, indicating its potential as a viable candidate for further development and evaluation as a recombinant vaccine against NDV.

Readiness to manage Ebola Virus Disease among emergency healthcare workers in Uganda: a nationwide multicenter survey

BackgroundEmerging infectious diseases like the Ebola Virus Disease (EVD) pose significant global public health threats. Uganda has experienced multiple EVD outbreaks, the latest occurring in 2022. Frontline healthcare workers (HCWs) are at increased risk, yet there is insufficient evidence of existing knowledge of EVD of these HCWs. We aimed to assess the readiness of Uganda’s emergency HCWs to manage EVD and identify their training needs to inform targeted capacity-building interventions for future outbreaks.MethodsThis multicentre nationwide cross-sectional study was conducted from July to September 2023 among HCWs providing emergency care in 14 secondary and tertiary hospitals across Uganda. Participants were consecutively recruited using the probability-proportional-to-size sampling technique, and data was collected using a self-reported questionnaire. Factors associated with EVD knowledge were identified through a mixed-effect linear model.ResultsData from 691 eligible HCWs with a median age of 32 (IQR: 28–38) was analyzed (response rate: 92%). Only one-third (34.4%, n = 238) had received EVD training in the past year. The median EVD knowledge score was 77.4% (IQR: 71.2 − 83.4%). EVD knowledge was associated with longer professional experience in years (β: 0.21, 95% CI: 0.03 to 0.39, p = 0.024) and higher level of education: diploma (β: 3.37, 95% CI: 1.49 to 5.25, p < 0.001), undergraduate degree (β: 6.45, 95% CI: 4.11 to 8.79) and postgraduate degree (β: 7.13, 95% CI: 4.01 to 10.25, p < 0.001). Being a doctor (β: 2.55, 95% CI: 0.35 to 4.74, p = 0.023), providing care in the obstetrics/gynecology department (β: −1.90, 95% CI: −3.47 to − 0.32, p = 0.018), previous EVD training (β: 2.27, 95% CI: 0.96 to 3.59, p = 0.001) and accessing EVD information through social media (β: 2.52, 95% CI: 1.17 to 3.88, p < 0.001) were also significantly associated with EVD knowledge. HCWs were mostly interested in training on management (92.9%), infection prevention and control (87.1%), and clinical presentation (84.1%), and preferred physical (51.5%) and hybrid (38.2%) training modes.ConclusionOur study shows that the readiness of HCWs in Uganda to respond to EVD outbreaks varies by individual factors and information sources. We recommend targeted training and suggest future research on educational innovations and social media’s potential to fill knowledge gaps.

Multilayer Nanocarrier for the Codelivery of Interferons: A Promising Strategy for Biocompatible and Long-Acting Antiviral Treatment

Background: Interferons (IFNs) are cytokines involved in the immune response with a synergistic regulatory effect on the immune response. They are therapeutics for various viral and proliferative conditions, with proven safety and efficacy. Their clinical application is challenging due to the molecules’ size, degradation, and pharmacokinetics. We are working on new drug delivery systems that provide adequate therapeutic concentrations for these cytokines and prolong their half-life in the circulation, such as nanoformulations. Methods: Through nanoencapsulation using electrospray technology and biocompatible and biodegradable polymers, we are developing a controlled release system based on nanoparticles for viral infections of the respiratory tract. Results: We developed a controlled release system for viral respiratory tract infections. A prototype nanoparticle with a core was created, which hydrolyzed the polyvinylpyrrolidone (PVP) shell , releasing the active ingredients interferon-alpha (IFN-α) and interferon-gamma (IFN-γ). The chitosan (QS) core degraded slowly, with a controlled release of IFN-α. The primary and rapid effect of the interferon combination ensured an antiviral and immunoregulatory response from day one, induced by IFN-α and enhanced by IFN-γ. The multilayer design demonstrated an optimal toxicity profile. Conclusions: This formulation is an inhaled dry powder intended for the non-invasive intranasal route. The product does not require a cold chain and has the potential for self-administration in the face of emerging viral infections. This novel drug has applications in multiple infectious, oncological, and autoimmune conditions, and further development is proposed for its therapeutic potential. This prototype would ensure greater bioavailability, controlled release, fewer adverse effects, and robust biological action through the simultaneous action of both molecules.