Displaying publications 861 - 880 of 1515 in total

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  1. Tan SC, Ankathil R
    Tumour Biol., 2015 Sep;36(9):6633-44.
    PMID: 26242271 DOI: 10.1007/s13277-015-3868-2
    Cervical cancer is a common malignancy which poses a significant health burden among women, especially those living in the developing countries. Although human papillomavirus (HPV) infection has been unequivocally implicated in the etiopathogenesis of the cancer, it alone is not adequate to contribute to the malignant transformation of cervical cells. Most HPV infections regress spontaneously, and only a small proportion of women have persistent infections which eventually lead to malignancy. This suggests that interplays between HPV infection and other cofactors certainly exist during the process of cervical carcinogenesis, which synergistically contribute to the differential susceptibility of an individual to the malignancy. Undoubtedly, host genetic factors represent a major element involved in such a synergistic interaction, and accumulating evidence suggests that polymorphisms in apoptosis-related genes play an important role in the genetic susceptibility to cervical cancer. This review consolidates the recent literatures on the role of common polymorphisms in apoptosis-related genes in genetic susceptibility to cervical cancer.
    Matched MeSH terms: Uterine Cervical Neoplasms/virology
  2. Cheong HT, Chow WZ, Takebe Y, Chook JB, Chan KG, Al-Darraji HA, et al.
    PLoS One, 2015;10(7):e0133883.
    PMID: 26196131 DOI: 10.1371/journal.pone.0133883
    In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.
    Matched MeSH terms: HIV Infections/virology*
  3. Ibrahim A, Ghazali WSW, Misyail A, Najwa L, Khan AH, Amir WM, et al.
    BMC Neurol, 2023 Mar 22;23(1):117.
    PMID: 36949469 DOI: 10.1186/s12883-023-03170-1
    BACKGROUND: There is a growing body of evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 infection is associated with the development of autoimmune diseases. A recent systematic review reported that the new-onset autoimmune disorders during or after COVID-19 infection included inflammatory myopathies such as immune-mediated necrotizing myopathies.

    CASE PRESENTATION: We described a 60-year-old man diagnosed with COVID-19 infection and later presented with a two-week history of myalgia, progressive limb weakness, and dysphagia. He had a Creatinine Kinase (CK) level of more than 10,000 U/L, was strongly positive for anti-signal recognition particle (SRP) and anti-Ro52 antibody, and a muscle biopsy revealed a paucity-inflammation necrotizing myopathy with randomly distributed necrotic fibers, which was consistent with necrotizing autoimmune myositis (NAM). He responded well clinically and biochemically to intravenous immunoglobulin, steroids and immunosuppressant and he was able to resume to his baseline.

    CONCLUSION: SARS-CoV-2 may be associated with late-onset necrotizing myositis, mimicking autoimmune inflammatory myositis.

    Matched MeSH terms: Myalgia/virology
  4. Ayed M, Borahmah AA, Yazdani A, Sultan A, Mossad A, Rawdhan H
    Med Princ Pract, 2021;30(2):185-192.
    PMID: 33197912 DOI: 10.1159/000513047
    OBJECTIVE: The objective of this study was to assess the clinical characteristics and identify mortality risk factors in intensive care unit (ICU)-admitted COVID-19 patients.

    METHODS: We recruited and analyzed SARS-CoV-2-infected adult patients (age ≥18 years) who were admitted to the ICU at Jaber Al-Ahmad Al Sabah Hospital, Kuwait, between March 1, 2020, and April 30, 2020. The risk factors associated with in-hospital mortality were assessed using multiple regression analysis.

    RESULTS: We recruited a total of 103 ICU patients in this retrospective cohort. The median age of the patients was 53 years and the fatality rate was 45.6%; majority (85.5%) were males and 37% patients had more than 2 comorbidities. Preexisting hypertension, moderate/severe acute respiratory distress syndrome, lymphocyte count <0.5 × 109, serum albumin <22 g/L, procalcitonin >0.2 ng/mL, D-dimer >1,200 ng/mL, and the need for continuous renal replacement therapy were significantly associated with mortality.

    CONCLUSION: This study describes the clinical characteristics and risk factors for mortality among ICU patients with CO-VID-19. Early identification of risk factors for mortality might help improve outcomes.

    Matched MeSH terms: Pneumonia, Viral/virology
  5. Pedrera M, McLean RK, Medfai L, Thakur N, Todd S, Marsh G, et al.
    Front Immunol, 2024;15:1384417.
    PMID: 38726013 DOI: 10.3389/fimmu.2024.1384417
    Nipah virus (NiV) poses a significant threat to human and livestock populations across South and Southeast Asia. Vaccines are required to reduce the risk and impact of spillover infection events. Pigs can act as an intermediate amplifying host for NiV and, separately, provide a preclinical model for evaluating human vaccine candidate immunogenicity. The aim of this study was therefore to evaluate the immunogenicity of an mRNA vectored NiV vaccine candidate in pigs. Pigs were immunized twice with 100 μg nucleoside-modified mRNA vaccine encoding soluble G glycoprotein from the Malaysia strain of NiV, formulated in lipid nanoparticles. Potent antigen-binding and virus neutralizing antibodies were detected in serum following the booster immunization. Antibody responses effectively neutralized both the Malaysia and Bangladesh strains of NiV but showed limited neutralization of the related (about 80% amino acid sequence identity for G) Hendra virus. Antibodies were also capable of neutralizing NiV glycoprotein mediated cell-cell fusion. NiV G-specific T cell cytokine responses were also measurable following the booster immunization with evidence for induction of both CD4 and CD8 T cell responses. These data support the further evaluation of mRNA vectored NiV G as a vaccine for both pigs and humans.
    Matched MeSH terms: Swine Diseases/virology
  6. Gilbert-Jaramillo J, Komarasamy TV, Balasubramaniam VR, Heather LC, James WS
    Antiviral Res, 2024 Aug;228:105933.
    PMID: 38851593 DOI: 10.1016/j.antiviral.2024.105933
    The underlying threat of new Zika virus (ZIKV) outbreaks remains, as no vaccines or therapies have yet been developed. In vitro research has shown that glycolysis is a key factor to enable sustained ZIKV replication in neuroprogenitors. However, neither in vivo nor clinical investigation of glycolytic modulators as potential therapeutics for ZIKV-related fetal abnormalities has been conducted. Accordingly, we tested the therapeutic potential of metabolic modulators in relevant in vitro systems comprising two pools of neuroprogenitors (NPCs), which resemble early and late stages of pregnancy. Effective doses of metabolic modulators [3.0 μM] dimethyl fumarate (DMF), [3.2 mM] dichloroacetate (DCA), and [6.3 μM] VER-246608 were determined for these cells by their effect on lactate release, pyruvate dehydrogenase (PDH) activity and cell survival. The drugs were used in a 24h pre-treatment and kept throughout ZIKV infection of NPCs. Drug effects and ZIKV replication were assessed at 24- and 56-h post-infection. In early NPCs treated with DMF, DCA and VER-246608, there was a significant reduction in the extracellular release of ZIKV potentially by PDH-mediated increased mitochondrial oxidation of glucose. Out of the three drugs, only DCA was observed to reduce viral replication in late NPCs treated with DCA. Altogether, our findings suggest that reduction of anaerobic glycolysis could be of therapeutic potential against ZIKV-related fetal abnormalities and that clinical translation should consider the use of specific glycolytic modulators over different trimesters.
    Matched MeSH terms: Neural Stem Cells/virology
  7. De Rubis G, Paudel KR, Yeung S, Mohamad S, Sudhakar S, Singh SK, et al.
    Pathol Res Pract, 2024 May;257:155295.
    PMID: 38603841 DOI: 10.1016/j.prp.2024.155295
    Tobacco smoking is a leading cause of preventable mortality, and it is the major contributor to diseases such as COPD and lung cancer. Cigarette smoke compromises the pulmonary antiviral immune response, increasing susceptibility to viral infections. There is currently no therapy that specifically addresses the problem of impaired antiviral response in cigarette smokers and COPD patients, highlighting the necessity to develop novel treatment strategies. 18-β-glycyrrhetinic acid (18-β-gly) is a phytoceutical derived from licorice with promising anti-inflammatory, antioxidant, and antiviral activities whose clinical application is hampered by poor solubility. This study explores the therapeutic potential of an advanced drug delivery system encapsulating 18-β-gly in poly lactic-co-glycolic acid (PLGA) nanoparticles in addressing the impaired antiviral immunity observed in smokers and COPD patients. Exposure of BCi-NS1.1 human bronchial epithelial cells to cigarette smoke extract (CSE) resulted in reduced expression of critical antiviral chemokines (IP-10, I-TAC, MIP-1α/1β), mimicking what happens in smokers and COPD patients. Treatment with 18-β-gly-PLGA nanoparticles partially restored the expression of these chemokines, demonstrating promising therapeutic impact. The nanoparticles increased IP-10, I-TAC, and MIP-1α/1β levels, exhibiting potential in attenuating the negative effects of cigarette smoke on the antiviral response. This study provides a novel approach to address the impaired antiviral immune response in vulnerable populations, offering a foundation for further investigations and potential therapeutic interventions. Further studies, including a comprehensive in vitro characterization and in vivo testing, are warranted to validate the therapeutic efficacy of 18-β-gly-PLGA nanoparticles in respiratory disorders associated with compromised antiviral immunity.
    Matched MeSH terms: Epithelial Cells/virology
  8. Wang Y, Li C, Zhao S, Wei Y, Li K, Jiang X, et al.
    PLoS Negl Trop Dis, 2024 Apr;18(4):e0012158.
    PMID: 38683870 DOI: 10.1371/journal.pntd.0012158
    Vector-borne infectious disease such as dengue fever (DF) has spread rapidly due to more suitable living environments. Considering the limited studies investigating the disease spread under climate change in South and Southeast Asia, this study aimed to project the DF transmission potential in 30 locations across four South and Southeast Asian countries. In this study, weekly DF incidence data, daily mean temperature, and rainfall data in 30 locations in Singapore, Sri Lanka, Malaysia, and Thailand from 2012 to 2020 were collected. The effects of temperature and rainfall on the time-varying reproduction number (Rt) of DF transmission were examined using generalized additive models. Projections of location-specific Rt from 2030s to 2090s were determined using projected temperature and rainfall under three Shared Socioeconomic Pathways (SSP126, SSP245, and SSP585), and the peak DF transmissibility and epidemic duration in the future were estimated. According to the results, the projected changes in the peak Rt and epidemic duration varied across locations, and the most significant change was observed under middle-to-high greenhouse gas emission scenarios. Under SSP585, the country-specific peak Rt was projected to decrease from 1.63 (95% confidence interval: 1.39-1.91), 2.60 (1.89-3.57), and 1.41 (1.22-1.64) in 2030s to 1.22 (0.98-1.51), 2.09 (1.26-3.47), and 1.37 (0.83-2.27) in 2090s in Singapore, Thailand, and Malaysia, respectively. Yet, the peak Rt in Sri Lanka changed slightly from 2030s to 2090s under SSP585. The epidemic duration in Singapore and Malaysia was projected to decline under SSP585. In conclusion, the change of peak DF transmission potential and disease outbreak duration would vary across locations, particularly under middle-to-high greenhouse gas emission scenarios. Interventions should be considered to slow down global warming as well as the potential increase in DF transmissibility in some locations of South and Southeast Asia.
    Matched MeSH terms: Aedes/virology
  9. Ang WX, Tan SH, Wong KT, Perera D, Kuppusamy UR, Ong KC
    Trop Biomed, 2024 Sep 01;41(3):241-250.
    PMID: 39548776 DOI: 10.47665/tb.41.3.002
    Hand, Foot and Mouth Disease (HFMD), a highly contagious viral disease common among infants and young children, is primarily caused by Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CVA16). Nonetheless, emerging enteroviruses, such as CV-A10 and CV-A6, have also caused widespread outbreaks globally, in part due to the absence of effective antiviral therapies, and the high personto-person transmission rate. Person-to-person transmission is usually through fecal-oral or oral-oral routes, and sometimes via droplets. As the oral cavity is a primary site for early virus infection and replication, controlling oral viral shedding can mitigate the risk of transmission through this route. Povidone-iodine (PVP-I), a widely used antiseptic, has shown broad-spectrum antimicrobial properties but antiviral studies against HFMD-causing enteroviruses are limited, especially for CV-A10 and CVA6. Our study demonstrated that a 1% PVP-I solution (final concentration of 0.5%) exhibited virucidal activity against EV-A71, CV-A16, CV-A10, and CV-A6. All seven EV-A71 isolates and five CV-A16 isolates showed a significant virus titer reduction after a 1-minute incubation, while five CV-A10 isolates and two CV-A6 isolates required a 5-minute incubation to achieve this. The virucidal activity was confirmed through the EN14476:2013+A2:2019 virucidal quantitative suspension test, wherein all four viruses were completely inactivated after a 30-minute incubation with PVP-I at 37°C under both clean and dirty conditions. Western blot analysis suggested that PVP-I could affect the VP1 structural proteins of EV-A71. Our results suggest that PVP-I could serve as a potential virucidal agent to reduce the risk of person-to-person transmission of HFMD.
    Matched MeSH terms: Hand, Foot and Mouth Disease/virology
  10. Lasso G, Grodus M, Valencia E, DeJesus V, Liang E, Delwel I, et al.
    Cell Host Microbe, 2025 Feb 12;33(2):294-313.e11.
    PMID: 39818205 DOI: 10.1016/j.chom.2024.12.016
    Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species. We found that GP-NPC1 binding correlated poorly with phylogeny. By integrating binding assays with machine learning, we identified genetic factors influencing virus-receptor-binding and predicted GP-NPC1-binding avidity for additional filoviruses and bats. Moreover, combining receptor-binding avidities with bat geographic distribution and the locations of previous Ebola outbreaks allowed us to rank bats by their potential as Ebola virus hosts. This study represents a comprehensive investigation of filovirus-receptor binding in bats (1,484 GP-NPC1 pairs, 11 filoviruses, and 135 bats) and describes a multidisciplinary approach to predict susceptible species and guide filovirus host surveillance.
    Matched MeSH terms: Filoviridae Infections/virology
  11. Jerip AR, Noni V, Anthony VK, Bong ACS, Adam J, Tan CS
    BMC Infect Dis, 2025 Mar 03;25(1):304.
    PMID: 40033233 DOI: 10.1186/s12879-025-10714-y
    BACKGROUND: Cervical cancer, primarily caused by persistent high-risk human papillomavirus (hrHPV) infections, is a significant health burden, particularly in low-resource settings such as Sarawak, Malaysia. Effective prevention depends on effective vaccination and early hrHPV detection. This study compares the performance of the point-of-care test (POCT) SD Biosensor Standard™ M10 HPV and laboratory-based Seegene Anyplex™ II HPV HR assay, focusing on their ability to detect and genotype hrHPV in self-collected high vaginal swab samples.

    METHODS: A total of 151 archived self-sampled high vaginal swabs from the Sarawak Urban and Rural Action for Cervical Cancer Elimination Programme (Program SUARA) were analyzed. hrHPV detection and genotyping were performed using Anyplex, which identifies 14 hrHPV genotypes, and M10, which detects HPV16, HPV18, and other hrHPV categorized into six genogroups. Agreement between the assays was evaluated using Cohen's Kappa (κ), McNemar's test, and overall agreement percentages. Statistical significance was determined with p-values, and discordant results were further analyzed for potential diagnostic implications.

    RESULTS: The overall agreement between M10 and Anyplex for hrHPV detection was 92.05% (κ = 0.84, 95% CI 0.75-0.93), indicating almost perfect agreement. M10 demonstrated comparable sensitivity for detecting HPV16, HPV18, and other hrHPV genotypes, achieving 96.91% agreement (κ = 0.89, 95%CI 0.73-1.00) in hrHPV classification when discordant results were excluded. Genogrouping also showed almost perfect agreement (κ = 0.91, 95% CI 0.82-0.98). McNemar's test indicated no significant difference in hrHPV detection rates (p > 0.05), affirming their comparable performance in detecting clinically significant hrHPV infections.

    CONCLUSION: The SD Biosensor Standard™ M10 HPV POCT and the Seegene Anyplex™ II HPV HR assay demonstrated almost perfect agreement in hrHPV detection and classification, supporting their complementary roles in cervical cancer prevention. M10's rapid, field-deployable design makes it suitable for resource-limited settings, while Anyplex provides enhanced genotyping capability in laboratory environments, allowing informed vaccine strategy. Incorporating both assays into cervical cancer prevention programs can improve screening coverage and accessibility, particularly in underserved areas. These findings align with the World Health Organization's cervical cancer elimination goals, reinforcing the importance of adaptable diagnostic tools in diverse healthcare contexts.

    Matched MeSH terms: Uterine Cervical Neoplasms/virology
  12. Nordin NA, Soon S, Senawi JB, Jinin ZAM, Arshad SS, Yasmin AR, et al.
    Appl Biochem Biotechnol, 2025 Mar;197(3):1760-1772.
    PMID: 39607468 DOI: 10.1007/s12010-024-05093-0
    Foot-and-mouth disease (FMD) is known for its highly contagious properties among cloven-hoofed animals resulting in significant morbidity rates. Incursions of this disease have caused significant losses in affected countries in Southeast Asia and Africa, even within EU countries which resulted in significant financial losses. This study is aimed at addressing existing limitations by creating a diagnostic method using aptamer-based assay. Three DNA aptamers were engineered to target the VP2 region of the FMD viral capsid protein. Since VP2 demonstrates a highly conserved amino acid sequence across serotypes, the specifically designed aptamers can detect different serotypes of the virus. Aptamers were evaluated against VP2 capsid protein, which was synthesized based on sequences from serotypes A, O, and Asia 1 of the FMD virus. After the recombinant VP2 capsid protein was developed, expressed, and refined, it was applied using enzyme-linked aptamer sorbent assay (ELASA) to determine aptamers' binding capability. A similar test was further conducted with purified FMD virus from serotype A and serotype O. The ELASA results displayed a notable sensitivity in identifying the FMDV. Under optimized conditions, the aptamers have LOD as low as 0.11 ng/mL with LOQ as low as 0.34 ng/mL. The binding strength analyzed using the equilibrium dissociation constant (Kd) showed strong binding affinity at 3.092 ± 0.05 nM. Based on these findings, the method shows significant potential with high sensitivity and specificity for FMD virus detection assay.
    Matched MeSH terms: Foot-and-Mouth Disease/virology
  13. Tee HS, Liang J, Aziz NA, Zhou X, Hisham HA, Tan KE, et al.
    J Med Virol, 2025 Mar;97(3):e70269.
    PMID: 40042148 DOI: 10.1002/jmv.70269
    Epstein-Barr virus (EBV) is associated with cancers, including lymphomas and nasopharyngeal carcinoma (NPC). To date, risk variants for NPC were mainly identified from Chinese populations, which dominated the world's total number of cases. Although Southeast Asia (SEA) countries have among the world's top yet intriguingly diverse NPC age-standardized incidence rates across subpopulations, data on EBV from SEA remains scarce. In this study, we examined 83 NPC patients of different ancestries for the presence of risk haplotypes associated with the Southern Chinese NPC and generated and analyzed 67 EBV sequences (from tissue, patient-derived xenografts and lymphoblastoid cell lines of 60 NPC patients) together with 838 published EBV genomes. Our study revealed that NPC patients of non-Chinese ancestry had fewer risk variants and haplotypes that are associated with Southern Chinese NPC and clustered distinctly from lymphomas, Southern Chinese NPC, and non-cancer controls. The distribution of non-synonymous variants was similar among NPC patients of Chinese ancestry, irrespective of geographical location. Meanwhile, non-synonymous variants in genes related to packaging, latency, and structural proteins such as BPLF1, LF3, and LMP1 varied across different ancestries. Our findings suggest possibilities of EBV adaptation to host genetics for NPC pathogenesis and warrant further research for the understudied NPC subpopulations.
    Matched MeSH terms: Carcinoma/virology
  14. Thavaraj S, Robinson M, Dayal S, Bowen C
    Diagn Pathol, 2025 Jan 24;20(1):9.
    PMID: 39856694 DOI: 10.1186/s13000-025-01601-w
    BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer death globally, with newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) cases rising to 54,000 in the US alone in the year 2022. Recently, human papilloma virus (HPV) infection was more prevalent in OPSCC patients than the traditionally known carcinogens such as tobacco or alcohol. HPV 16 is the most common causative HPV strain, which is found in 5-10% of HNSCC patients. HPV 16's E6 and E7 oncoproteins bind and inactivate p53 and retinoblastoma (Rb) tumor-suppressing genes. This causes aberrant over-expression of the cell cycle inhibitor gene, p16, leading to tumorigenesis. Leica Biosystems (LBS) has developed a p16 antibody (6H12 clone) for qualitatively identifying the p16 protein in formalin-fixed paraffin-embedded (FFPE) tissue by immunohistochemical staining. This method comparison study tested the concordance rates between ready-to-use (RTU) LBS p16/LBS RTU p16 antibody and Roche Tissue Diagnostics (RTD) CINtec p16 Histology immunohistochemical (IHC) assays by measuring overall agreement (OA), average positive agreement (APA), and average negative agreement (ANA) rates in 170 OPSCC FFPE cases. Interobserver agreement of the 2 assays and LBS RTU p16 comparison with the standard HPV molecular assays (DNA ISH and PCR) were also assessed.

    METHODS: One hundred and seventy (170) unique oropharyngeal cancer cases were stained for qualitative analysis by the LBS p16 antibody on BOND III. This assay was compared to Ventana's RTD E6H4 (CINtec) clone on Benchmark XT. A stained core was considered p16 positive if the Histoscore (H score) was ≥ 140 and negative if H 

    Matched MeSH terms: Carcinoma, Squamous Cell/virology
  15. Tham HY, Chong LC, Krishnan M, Khan AM, Choi SB, Tamura T, et al.
    Arch Microbiol, 2025 Jan 29;207(2):47.
    PMID: 39878790 DOI: 10.1007/s00203-025-04242-1
    Bacteriophages produce endolysins at the end of the lytic cycle, which are crucial for lysing the host cells and releasing virion progeny. This lytic feature allows endolysins to act as effective antimicrobial alternatives when applied exogenously. Staphylococcal endolysins typically possess a modular structure with one or two enzymatically active N-terminal domains (EADs) and a C-terminal cell wall binding domain (CBD). The EADs degrade the peptidoglycan layer, leading to bacterial lysis, while the CBD binds to the specific host cell wall, and therefore, influences specificity of the endolysin. This study aimed to alter and characterize the host specificity of the CBD by exploring the impact of amino acid modifications within the CBD of a staphylococcal endolysin, Endo88. Endo88 was able to lyse Staphylococcus spp. and Enterococcus faecalis. However, despite attempts to mutate amino acids hypothesized for binding with cell wall components, the host-range was not affected but the lytic activity was severely reduced instead, although no alterations were performed on the EADs (Cysteine, histidine-dependent aminohydrolases/peptidases domain and Amidase domain). Further investigations of the CBD alone (Src homology3 domain, SH3) without the EADs suggested that binding and lytic activity may not be correlated in some cases since Endo88 and its mutants could lyse Staphylococcus epidermidis well but no binding activity was observed in the flow cytometry analysis. Molecular docking was used to gain insights on the observations for the binding and lytic activity which may help future strategies in designing enhanced engineered endolysins.
    Matched MeSH terms: Enterococcus faecalis/virology
  16. Reynard O, Iampietro M, Dumont C, Le Guellec S, Durand S, Moroso M, et al.
    Antiviral Res, 2025 Mar;235:106095.
    PMID: 39870114 DOI: 10.1016/j.antiviral.2025.106095
    Nipah virus (NiV) is a lethal zoonotic paramyxovirus that can be transmitted from person to person through the respiratory route. There are currently no licensed vaccines or therapeutics. A lipopeptide-based fusion inhibitor was developed and previously evaluated for efficacy against the NiV-Malaysia strain. Intraperitoneal administration in hamsters showed superb prophylactic activity and promising efficacy, however the intratracheal delivery mode in non-human primates proved intractable and spurred the development of an aerosolized delivery route that could be clinically applicable. We developed an aerosol delivery system in an artificial respiratory 3D model and optimized the combinations of flow rate and particle size for lung deposition. We characterized the nebulizer device and assessed the safety of lipopeptide nebulization in an African green monkey model that mimics human NiV infection. Three nebulized doses of fusion-inhibitory lipopeptide were administered every 24 h, resulting in peptide deposition across multiple regions of both lungs without causing toxicity or adverse hematological and biochemical effects. In peptide-treated monkeys challenged with a lethal dose of NiV-Bangladesh, animals retained robust levels of T and B-lymphocytes in the blood, infection-induced lethality was significantly delayed, and 2 out of 5 monkeys were protected from NiV infection. The present study establishes the safety and feasibility of the nebulizer delivery method for AGM studies. Future studies will compare delivery methods using next-generation fusion-inhibitory anti-NiV lipopeptides to evaluate the potential role of this aerosol delivery approach in achieving a rapid antiviral response.
    Matched MeSH terms: Lung/virology
  17. Pandey P, Ranjan R, Agarwal P, Gupta RM, Pandey AK, Das A, et al.
    Trop Biomed, 2024 Dec 01;41(4):464-470.
    PMID: 39876504 DOI: 10.47665/tb.41.4.007
    Examining the co-circulation of various serotypes and finding serotypes linked to illness severity were the main objectives of this study, which sought to investigate the epidemiology and serotype distribution of dengue in Haryana, North India. The cross-sectional study, which was carried out in a tertiary care hospital between September 2021 and April 2023, enrolled participants who met WHO criteria for probable dengue fever. Blood samples underwent molecular and serological diagnostics, such as immunochromatographic testing, VIDAS® Dengue NS1 assays, and TRUPCR® Dengue Detection and serotyping kits, in addition to the collection of clinical and demographic data. Dengue was found to be present in 212 of the 536 probable cases, with serotype DENV-2 being the most common. There have also been reports of mixed DENV-1 and DENV-2 infections. Different serotypes caused different lengths of sickness; DENV-2 showed a sustained high RT-PCR positivity. The severity of the disease was linked to distinct serotypes based on significant differences in aspartate aminotransferase (AST) levels between individuals with dengue fever (DF) and dengue haemorrhagic fever (DHF). The study emphasizes how complicated dengue virus infections can be because of the co-circulation of several serotypes and the possibility of mixed infections. Serotypes and illness severity are correlated, which emphasizes the necessity of continuous surveillance and monitoring to improve outbreak prediction and management. These results are critical for guiding clinical judgments and public health policy, especially with relation to the possible introduction of a dengue vaccine.
    Matched MeSH terms: Coinfection/virology
  18. Butler D
    Nature, 2004 May 6;429(6987):7.
    PMID: 15129247
    Matched MeSH terms: Chiroptera/virology*
  19. Bala JA, Balakrishnan KN, Abdullah AA, Mohamed R, Haron AW, Jesse FFA, et al.
    Microb Pathog, 2018 Jul;120:55-63.
    PMID: 29709684 DOI: 10.1016/j.micpath.2018.04.057
    Orf disease is known to be enzootic among small ruminants in Asia, Africa, and some other parts of the world. The disease caused by orf virus is highly contagious among small ruminant species. Unfortunately, it has been neglected for decades because of the general belief that it only causes a self-limiting disease. On the other hand, in the past it has been reported to cause huge cumulative financial losses in livestock farming. Orf disease is characterized by localized proliferative and persistent skin nodule lesions that can be classified into three forms: generalized, labial and mammary or genitals. It can manifest as benign or malignant types. The later type of orf can remain persistent, often fatal and usually causes a serious outbreak among small ruminant population. Morbidity and mortality rates of orf are higher especially in newly infected kids and lambs. Application of antibiotics together with antipyretic and/or analgesic is highly recommended as a supportive disease management strategy for prevention of subsequent secondary microbial invasion. The presence of various exotic orf virus strains of different origin has been reported in many countries mostly due to poorly controlled cross-border virus transmission. There have been several efforts to develop orf virus vaccines and it was with variable success. The use of conventional vaccines to control orf is a debatable topic due to the concern of short term immunity development. Following re-infection in previously vaccinated animals, it is uncommon to observe the farms involved to experience rapid virus spread and disease outbreak. Meanwhile, cases of zoonosis from infected animals to animal handler are not uncommon. Despite failures to contain the spread of orf virus by the use of conventional vaccines, vaccination of animals with live orf virus is still considered as one of the best choice. The review herein described pertinent issues with regard to the development and use of potential effective vaccines as a control measure against orf virus infection.
    Matched MeSH terms: Ecthyma, Contagious/virology; Sheep Diseases/virology; Zoonoses/virology; Communicable Diseases, Emerging/virology
  20. Higuchi H, Yamakawa N, Imadome KI, Yahata T, Kotaki R, Ogata J, et al.
    Blood, 2018 06 07;131(23):2552-2567.
    PMID: 29685921 DOI: 10.1182/blood-2017-07-794529
    Epstein-Barr virus (EBV) causes various diseases in the elderly, including B-cell lymphoma such as Hodgkin's lymphoma and diffuse large B-cell lymphoma. Here, we show that EBV acts in trans on noninfected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between 2 EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata-derived exosomes affected LPD severity, possibly through the regulation of macrophage phenotype in vivo. Exosomes collected from Akata-lymphoblastoid cell lines reportedly contain EBV-derived noncoding RNAs such as BamHI fragment A rightward transcript (BART) micro-RNAs (miRNAs) and EBV-encoded RNA. We focused on the exosome-mediated delivery of BART miRNAs. In vitro, BART miRNAs could induce the immune regulatory phenotype in macrophages characterized by the gene expressions of interleukin 10, tumor necrosis factor-α, and arginase 1, suggesting the immune regulatory role of BART miRNAs. The expression level of an EBV-encoded miRNA was strongly linked to the clinical outcomes in elderly patients with diffuse large B-cell lymphoma. These results implicate BART miRNAs as 1 of the factors regulating the severity of lymphoproliferative disease and as a diagnostic marker for EBV+ B-cell lymphoma.
    Matched MeSH terms: Inflammation/virology*; Lymphoma/virology*; Epstein-Barr Virus Infections/virology; Exosomes/virology*
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