Virus Infection Research Articles

Review of Thymic Peptides and Hormones: From Their Properties to Clinical Application

Abstract Background The thymus is the main lymphoid organ that regulates the functions of the immune system, protecting against pathogens, tumors, antigens, and mediators of tissue damage. It produces a family of hormone-like peptides that can modulate physiological processes such as stimulation or suppression of immune responses, angiogenesis, and wound healing. Objective This review aims to comprehensively characterize the properties of thymic peptides and their clinical applications. Methodology This article discusses the structure, biological properties, mechanism of action, and therapeutic applications of the most important thymic hormones (thymosin alpha 1, thymosin beta-4, thymulin, and thymopoietin), as well as preparations that are purified thymic extracts. Results Thymic peptides and extracts act in multiple manners on the immune system: they stimulate the differentiation and maturation of T cells, regulate the activity of natural killer cells and dendritic cells, and induce the release of proinflammatory cytokines, and their immunomodulatory effects have been confirmed in numerous clinical studies. An important feature of thymus preparations is their therapeutic safety—even long-term use does not cause side effects. Conclusions A wide range of therapeutic uses, i.e., from defensive and immunomodulatory tasks to participation in tissue regeneration processes, has led to the use of thymic peptides in the treatment of neoplastic diseases, viral infections, autoimmune diseases or immunodeficiencies. Further investigation of the mechanisms of action of thymic peptides may contribute to the discovery of new therapeutic targets.

Unlocking CD8+ T cell potential in chronic hepatitis B virus infection

Unlocking CD8+ T cell potential in chronic hepatitis B virus infection

Parenteral aciclovir for suspected herpes simplex virus infection in children: 0–18 years

Abstract Background Variations in neonatal aciclovir prescribing for suspected herpes simplex virus (HSV) disease are well-known, but there are limited data describing aciclovir prescribing in older children. Methods Medical records of neonates (≤28 days) and children (29 days to 18 years) prescribed intravenous aciclovir for suspected HSV disease (1 January 2019–12 December 2019) in eight Australian and New Zealand hospitals were reviewed. Prescribing indication, HSV testing, aciclovir prescription details, adverse events and discharge diagnosis were recorded. Results 1426 received empirical aciclovir. For neonates (n = 425), the median duration was 1 day (IQR 1–3), 411/425 underwent HSV investigations and 13/425 had HSV disease (two with disseminated encephalitis, four with encephalitis and seven with skin, eye, mouth disease). Of the 1001 children, 906 were immunocompetent. 136/906 suspected of mucocutaneous disease received aciclovir for a median of 2 days (1–2), 121/136 underwent HSV testing, and 69/136 had proven disease. 770/906 received aciclovir for suspected disseminated disease or encephalitis for a median of 1 day (1–2), 556/770 underwent HSV testing, and 5/770 had disseminated disease or encephalitis. Among 95 immunocompromised children, 53/58 with suspected mucocutaneous disease had HSV testing and this was confirmed in 22. Disseminated disease or encephalitis was suspected in 37/95, HSV testing conducted in 23/37 and detected in one. The median aciclovir duration was 3 (2–7) days for immunocompromised children. Nephrotoxicity occurred in 7/1426 and 24/1426 had an extravasation injury. Conclusion Frequent and often unnecessary intravenous aciclovir prescribing for suspected HSV encephalitis or disseminated disease occurred in children, as evidenced by incomplete HSV investigations and only 5/770 older children having the diagnosis confirmed.

Breaching the Barrier: Investigating Initial Herpes Simplex Viral Infection and Spread in Human Skin and Mucosa

Herpes simplex virus (HSV) is sexually transmitted via the anogenital mucosa where it initially infects epidermal keratinocytes and mononuclear phagocytes (MNPs). It then spreads to the dorsal root ganglion via sensory nerve endings, to remain latent for life with periodic reactivation. Currently, there is no cure or vaccine. Initial or recurrent HSV infection can produce serious complications and mediate acquisition of HIV. This review outlines the initial events after the HSV infection of human anogenital mucosa to determine the optimal window to target the virus before it becomes latent. After infection, HSV spreads rapidly within the mid-layers of epidermal keratinocytes in the explanted human inner foreskin. Infected cells produce chemokines, which modulate nectin-1 distribution on the surface of adjacent keratinocytes, facilitating viral spread. Epidermal Langerhans cells and dendritic cells become infected with HSV followed by a “viral relay” to dermal MNPs, which then present viral antigen to T cells in the dermis or lymph nodes. These data indicate the need for interruption of spread within 24 h by diffusible vaccine-induced mediators such as antiviral cytokines from resident immune cells or antibodies. Intradermal/mucosal vaccines would need to target the relevant dermal MNPs to induce HSV-specific CD4+ and CD8+ T cells.

Abstract C001: Cytomegalovirus infection modulates distinct immune cell dynamics across tumor-immune microenvironments and systemic macroenvironment during metastasis

Abstract Cytomegalovirus (CMV) is ubiquitously present worldwide and has been implicated in the modulation of cancer development and spread. Notably, CMV proteins have been detected in approximately 90% of lymph node and brain metastases in breast cancer, suggesting its potential influencing tumor invasiveness and metastases. This study investigates the effects of CMV infection on the tumor microenvironment and macroenvironment during metastatic progression in triple-negative breast cancer (TNBC). We employed a syngeneic TNBC mouse model designed to develop spontaneous metastases following primary tumor resection. Using multi-omics sequencing and comprehensive analysis tools, we characterized the tumor-immune landscape across multiple organs relevant to CMV infection and tumor metastasis, including blood, bone marrow, spleen, lungs, brain, and lymph nodes. Our results demonstrate that CMV infection systematically activated the immune response, suppressing primary tumor growth and subsequent metastasis. At the primary tumor site, prior to metastasis, CMV-infected mice exhibited significantly lower proportions of macrophages and plasma cells compared to uninfected counterparts, while CD8+ T cells were significantly enriched. In contrast, the proportions of neutrophils and dendritic cells did not significantly differ between the groups. Distinct patterns of immune cell dynamics were observed at metastatic sites. In the spleen of CMV-infected mice, a notable reduction in macrophages and elevated neutrophil levels were detected. Lung tissues displayed a marked increase in macrophages, CD8+ T cells, and dendritic cells in CMV-infected mice. Interestingly, in the blood, we noted a decreased proportion of natural killer cells in CMV-infected mice. However, no significant difference in plasma cell percentages was observed between CMV-infected and uninfected mice in metastatic lung tissues. The cell-cell interaction analysis further showed a complex crosstalk network between immune cells as well as tumor and immune cells. These findings highlight the profound impact of CMV infection on remodeling the immune landscape at both primary tumors and metastatic sites. The distinct immune cell dynamics orchestrated by CMV infection underscore the virus's role in modifying tumor-immune microenvironments and macroenvironments. Our study offers novel perspectives for developing targeted cancer therapies that consider the complex interactions between viral infections and the tumor immune axis. Further research is warranted to elucidate the mechanisms underlying CMV-mediated immune modulation at molecular level and its potential therapeutic implications in TNBC and other cancer types. Citation Format: Wenjuan Dong, Jianting Sheng, Shan Xu, Matthew Vasquez, Hong Zhao, Stephen T.C Wong. Cytomegalovirus infection modulates distinct immune cell dynamics across tumor-immune microenvironments and systemic macroenvironment during metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C001.

Abstract IA007: Respiratory viral infection promotes the awakening and outgrowth of dormant metastatic breast cancer cells in lungs

Abstract Breast cancer is the second most common cancer globally. Most deaths from breast cancer are due to metastatic disease which often follows long periods of clinical dormancy. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCC) is crucial for addressing metastatic progression. Infection with respiratory viruses (e.g. influenza or SARS-CoV-2) is common and triggers an inflammatory response locally and systemically. Here we show that influenza virus infection leads to loss of the pro-dormancy mesenchymal phenotype in breast DCC in the lung, causing DCC proliferation within days of infection, and a greater than 100-fold expansion of carcinoma cells into metastatic lesions within two weeks. Such DCC phenotypic change and expansion is interleukin-6 (IL-6)-dependent. We further show that CD4 T cells are required for the maintenance of pulmonary metastatic burden post-influenza virus infection, in part through attenuation of CD8 cell responses in the lungs. Single-cell RNA-seq analyses reveal DCC-dependent impairment of T-cell activation in the lungs of infected mice. SARS-CoV-2 infected mice also showed increased breast DCC expansion in lungs post-infection. Expanding our findings to human observational data, we observed that cancer survivors contracting a SARS-CoV-2 infection have substantially increased risks of lung metastatic progression and cancer-related death compared to cancer survivors who did not. These discoveries underscore the significant impact of respiratory viral infections on the resurgence of metastatic cancer, offering novel insights into the interconnection between infectious diseases and cancer metastasis. Citation Format: Shi B. Chia, Bryan J. Johnson, Junxiao Hu, Roel Vermeulen, Marc Chadeau-Hyam, Fernando Guntoro, Hugh Montgomery, Meher Boorgula, Varsha Sreekanth, Andrew Goodspeed, Bennett Davenport, Felipe Valenca-Pereira, Vadym Zaberezhnyy, Wolfgang E Schleicher, Dexiang Gao, Andreia N. Cadar, Michael Papanicolaou, Afshin Beheshti, Stephen B. Baylin, James Costello, Jenna M. Bartley, Thomas E. Morrison, Julio A. Aguirre-Ghiso, Mercedes Rincon, James DeGregori. Respiratory viral infection promotes the awakening and outgrowth of dormant metastatic breast cancer cells in lungs [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr IA007.

Implications of Asymptomatic Carriers for Tuberculosis Transmission and Control in Thailand: A Modelling Approach

Tuberculosis (TB) is a regional and global bacterial illness that has been expanding and affecting individuals in every generation. An unknown percentage of asymptomatic hosts have TB, and the infection can spread while exhibiting no symptoms. These asymptomatic TB carriers, who contribute to the spread of the illness yet go mostly undetected, may make it more difficult to prevent transmission. In this study, we utilized the concept of symmetry to construct a manageable disease modelling framework for TB transmission and control. We developed a TB model to investigate the potential influence of asymptomatic carriers, symptomatic infections, and the entirety of TB prevalence on different approaches to treatment and prevention in Thailand. Annual TB incidence data from Thailand from 2000 to 2022 were used to calibrate the model parameters. We assessed the potential for reaching conflicting results about the management and spread of tuberculosis in Thailand. Our results showed that some TB strategies that were thought to be effective in reducing transmission may have the opposite impact, or that an intervention’s effectiveness might be overestimated, making it seem unfeasible in certain scenarios. For example, the objective of TB treatment, which attempts to decrease the occurrence of symptomatic TB infections, is to decrease the TB infection and propagation rates if the relative carrier (η) is less than one. Nonetheless, our results indicate that this strategy may increase the frequency of asymptomatic TB patients, symptomatic TB viral infections, and overall TB prevalence if η has been sufficiently understated. We also found that reducing only the progression rate of symptomatic TB infections cannot stop asymptomatic TB carriers and total TB prevalence, even when the relative infection of carriers (η) is less than unity. Our research provides a better understanding of the role of asymptomatic patients in spreading TB and highlights the need to accurately include bearers in models that guide Thailand’s TB control strategy.

The Development of Epilepsy Following CNS Viral Infections: Mechanisms.

This review examines the role of different viral infections in epileptogenesis, with a focus on Herpesviruses such as Human Herpesvirus 6 (HHV-6) and Epstein Barr Virus (EBV), Flaviviruses, Picornaviruses, Human Immunodeficiency Virus (HIV), Influenzavirus and Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). A growing literature on animal models, such as the paradigmatic Theiler's murine encephalomyelitis virus (TMEV) model, and clinical investigations in patients with epilepsy have started to elucidate cellular mechanisms implicated in seizure initiation and development of epilepsy following viral infections. A central role of neuroinflammation has emerged, with evidence of activation of the innate and adaptive immunity, dysregulation of microglial and astrocytic activity and production of multiple cytokines and other inflammatory mediators. Several chronic downstream effects result in increased blood-brain barrier permeability, direct neuronal damage, and modifications of ion channels ultimately leading to altered neuronal excitability and seizure generation. Key findings underscore the complex interplay between initial viral infection, neuroinflammation, and later development of epilepsy. Further research is needed to elucidate these mechanisms and develop targeted interventions.

Exploring the Antiviral Potential of Artemisia annua Through JAK-STAT Pathway Targeting: A Network Pharmacology Approach

Background: Artemisia annua, a plant with antiviral potential, has shown promise against various viral infections, yet its mechanisms of action are not fully understood. This study explores A. annua’s antiviral effects using network pharmacology and molecular docking, focusing on key active compounds and their interactions with viral protein targets, particularly within the JAK-STAT signaling pathway—a critical mediator of immune responses to viral infections. Methods: From the TCMSP database, we identified eight active compounds and 335 drug targets for A. annua, with 19 intersecting targets between A. annua compounds and viral proteins. A protein–protein interaction (PPI) network highlighted 10 key hub genes, analyzed further through Gene Ontology (GO) and KEGG pathways to understand their immune and antiviral roles. ADMET properties of the active compound Patuletin (MOL004112) were assessed, followed by 200 ns molecular dynamics simulations to examine its stability in complex with JAK2. Results: PPI analysis identified JAK2, MAPK3, MAPK1, JAK1, PTPN1, HSPA8, TYK2, RAF1, MAPT, and HMOX1 as key hub genes, with JAK2 emerging as a critical regulator of immune and antiviral pathways. ADMET analysis confirmed Patuletin’s favorable pharmacokinetic properties, and molecular dynamics simulations showed a stable Patuletin-JAK2 complex, with FEL analysis indicating minimal disruption to JAK2’s intrinsic flexibility. Conclusions: These findings highlight JAK2 as a promising target in the antiviral activity of A. annua compounds, particularly Patuletin, supporting its potential as an antiviral agent and providing a foundation for further research on A. annua’s therapeutic applications.

A Case of Acute Necrotizing Encephalitis Misdiagnosed as Opium Poisoning: A Case Report

Introduction: The coronavirus has been associated with significant neurologic complications, including encephalopathy, seizures, ataxia, and motor or sensory deficits. Among these complications, acute necrotizing encephalopathy (ANE) is a rare condition linked to viral infections such as influenza, HHV-6, and COVID-19. This study presents a unique case of ANE in a COVID-19 patient, initially misdiagnosed as opium poisoning. Despite the reduction in pandemic cases, COVID-19 continues to present serious side effects, emphasizing the need to recognize potential neurological manifestations of the virus. Increased awareness and accurate diagnosis are essential for managing these complex cases. Case Presentation: This case study involves a 29-year-old female patient presenting with loss of consciousness and other symptoms that led to a diagnosis of COVID-19-related acute necrotizing encephalitis. Initial suspicions of opium poisoning were ruled out, and imaging tests revealed bilateral ground-glass opacities (GGO) and consolidation in the chest, along with abnormal findings in the brain. The patient was treated with glucocorticoid pulse therapy and IVIG, resulting in symptom improvement, though some neurological deficits persisted at discharge. This case underscores the importance of considering COVID-19 in cases of acute encephalitis and highlights the neurological complications associated with the virus. Conclusions: This study explores ANE as a severe manifestation of COVID-19 infection, focusing on the diverse neurological presentations associated with ANE in COVID-19 patients and a case initially misdiagnosed as opium poisoning. Through a case study of a patient with ANE, characterized by loss of consciousness and meiotic pupils, the research emphasizes the need for early detection and appropriate treatment. Findings suggest that ANE in COVID-19 patients can present with varied symptoms, posing diagnostic challenges. The study underscores the value of timely intervention with glucocorticoid pulse therapy and gamma globulin injection to improve patient outcomes. These findings highlight the necessity for increased awareness among healthcare providers to promptly recognize ANE in COVID-19 patients, aiding in timely and effective intervention.

Potential antiviral activity of rhamnocitrin against influenza virus H3N2 by inhibiting cGAS/STING pathway in vitro.

Influenza remains a serious issue for public health and it's urgent to discover more effected drugs against influenza virus. Rhamnocitrin, as a flavonoid, its effect on influenza virus infection remains poorly explored. In this study, rhamnocitrin showed antiviral effect and anti-apoptosis on influenza virus A/Aichi/2/1968 (H3N2) in MDCK cells and A549 cells. In addition, molecular docking revealed that rhamnocitrin have good binding activity with the target proteins cGAS and STING, molecular dynamic simulation and surface plasmon resonance showed that rhamnocitrin could form a stable complex with the above proteins. Moreover, the qPCR and western blot assays further verified that rhamnocitrin could reduce type I IFN and proinflammatory cytokines production by inhibiting the cGAS/STING pathway. Taken together, the results suggest that rhamnocitrin could be a potential anti-viral agent against influenza.

Diverse roles of phytohormonal signaling in modulating plant-virus interaction.

Virus infection brings about changes in the transcriptome, proteome and metabolome status of the infected plant wherein substantial alterations in the abundance of phytohormones and associated components involved in their signaling pathways have been observed. In the recent years, extensive research in the field of plant virology has showcased the undisputable significance of phytohormone signaling during plant-virus interactions. Apart from acting as growth regulators, phytohormones elicit robust immune response, which restricts the viral multiplication within the plant as well as its propagation by vector. Interestingly, these pathways have been shown to not only act as isolated mechanisms but as complex intertwined regulatory cascades where, the cross-talk among different phytohormones and with other antiviral pathways takes place during plant-virus interplay. Viruses cleverly disrupt phytohormone homeostasis via their multifunctional effectors that seems to be smart approach adopted by viruses to circumvent phytohormone-mediated plant immune responses. In this review, we summarize the current understanding of role of phytohormone signaling pathways during plant-virus interaction in activating antiviral immune responses of plant and also, how viruses exploit these signaling pathways favoring their pathogenesis.

Modeling extrahepatic hepatitis E virus infection in induced human primary neurons

Hepatitis E virus (HEV) infections are one of the most common causes of acute viral hepatitis, annually causing over 3 million symptomatic cases and 70,000 deaths worldwide. Historically, HEV was described as a hepatotropic virus, but has recently been associated with various extrahepatic manifestations including neurological disorders such as Guillain-Barré syndrome and neuralgic amyotrophy. However, the underlying pathogenesis of these neurological diseases remains largely unknown. The aim of this study was to investigate extrahepatic HEV manifestations in a neuronal model system using human-induced primary neurons (iPNs). Renal epithelial cells from human urine were reprogrammed to induced pluripotent stem cells to generate neuronal progenitor cells, which were subsequently differentiated into iPNs over 21 d. These iPNs supported HEV infection preferentially in neurite-bearing cells. Transcriptional profiling of the neuronal development process as well as viral infection dynamics in iPNs uncovered a lack of antiviral innate immune responses to HEV infection with only an intrinsic expression of distinct interferon-regulated genes and signaling molecules. Viral open reading frame 2 encoded capsid protein could be visualized by volumetric three-dimensional reconstitution within the neurites, which were reduced in length in an HEV inoculation-dependent manner. In conclusion, this neuron-derived human model system provides a powerful tool for studying extrahepatic manifestations of HEV infection. It further indicates a potential mechanism of pathogenesis driven by the interaction between host and viral factors.

Dermatological manifestations in diabetes mellitus and its relation with HbA1c levels – An observational study

Diabetes Mellitus is a chronic, metabolic disease characterised by elevated levels of blood glucose, which over time leads to serious damage. The most common is type 2 diabetes which occurs when body becomes resistant to insulin or doesn’t make enough insulin. Skin manifestations are seen generally in pre-diabetes, undiagnosed, long-term and uncontrolled diabetes mellitus. Skin symptoms may help in diagnosing a denovo case and may give an insight into the patient's diabetic status. This is a cross-sectional, observational study conducted in patients attending the outpatient departments of Dermatology, General Medicine and those admitted under these departments over a period of four months. Clearance from Institutional Ethics Committee was taken before the start of the study. A sample population of 100 was selected randomly based on inclusion and exclusion criteria. Glycaemic profiles including HbA1c were done. Infections (35%) were the most common cutaneous symptoms, followed by papulosquamous illnesses (19%), autoimmune diseases (7%), obesity-related (6%), diabetic vasculopathy-related (5%) and miscellaneous conditions (28%), which included generalised pruritus and xerosis etc. The majority of infections were superficial fungal infections, followed by bacterial and viral infections. Dermatophytosis accounted for a majority of superficial fungal infections. Significant correlation was found between higher HbA1c levels and infections, papulo-squamous diseases, auto-immune diseases, obesity-related manifestations.Higher HbA1c levels were found to be significantly associated with a variety of cutaneous symptoms such as infections, papulosquamous illnesses, autoimmune disorders, and obesity-related manifestations.

Exosome-mediated viral nucleic acid presentation in a crustacean expounds innate immunity from a novel perspective.

Our study revealed that the components of DNA virus could be packaged and transmitted through the exosomes of lower invertebrates, which strongly demonstrated the diversity of exosome-mediated viral immunity and its universality in animals. Furthermore, we elucidated the mechanism of apoptotic signal transduction between cells from the perspective of exosomes and revealed a novel strategy for the host to cope with viral infection.

The potential of lactoferrin as antiviral and immune-modulating agent in viral infectious diseases

Emerging infectious diseases are caused by unpredictable viruses with the dangerous potential to trigger global pandemics. These viruses typically initiate infection by utilizing the anionic structures of host cell surface receptors to gain entry. Lactoferrin (Lf) is a multifunctional glycoprotein with multiple properties such as antiviral, anti-inflammatory and antioxidant activities. Due to its cationic structure, Lf naturally interacts with certain host cell receptors, such as heparan sulfate proteoglycans, as well as viral particles and other receptors that are targeted by viruses. Therefore, Lf may interfere with virus-host cell interactions by acting as a receptor competitor for viruses. Herein we summarize studies in which this competition was investigated with SARS-CoV-2, Zika, Dengue, Hepatitis and Influenza viruses in vitro. These studies have demonstrated not only Lf’s competitive properties, but also its potential intracellular impact on host cells, such as enhancing cell survival and reducing infection efficiency by inhibiting certain viral enzymes. In addition, the immunomodulatory effect of Lf is highlighted, as it can influence the activity of specific immune cells and regulate cytokine release, thereby enhancing the host’s response to viral infections. Collectively, these properties promote the potential of Lf as a promising candidate for research in viral infectious diseases.

Targeting PRMT7-mediated monomethylation of MAVS enhances antiviral innate immune responses and inhibits RNA virus replication

RIG-I-like receptors (RLRs)-mitochondrial antiviral signaling protein (MAVS) are crucial for type I interferon (IFN) signaling pathway and innate immune responses triggered by RNA viruses. However, the regulatory molecular mechanisms underlying RNA virus-activated type I IFN signaling pathway remain incompletely understood. Here, we found that protein arginine methyltransferase 7 (PRMT7) serves as a negative regulator of the type I IFN signaling pathway by interacting with MAVS and catalyzing monomethylation of arginine 232 (R232me1) in MAVS. RNA virus infection leads to the downregulation and dissociation of PRMT7 from MAVS as well as the decrease of R232me1 methylation, enhancing MAVS/RIG-I interaction, MAVS aggregation, type I IFN signaling activation, and antiviral immune responses. Knock-in mice with MAVS R232 substituted with lysine (MavsR232K-KI) are more resistant to Vesicular Stomatitis Virus infection due to enhanced antiviral immune responses. PiPRMT7-MAVS, a short peptide inhibitor designed to interrupt the interaction between PRMT7 and MAVS, inhibits R232me1 methylation, thereby enhancing MAVS/RIG-I interaction, promoting MAVS aggregation, activating type I IFN signaling, and bolstering antiviral immune responses to suppress RNA virus replication. Moreover, the clinical relevance of PRMT7 is highlighted that it is significantly downregulated in RNA virus-infected clinical samples, such as blood samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ebola virus, as well as H1N1-infected bronchial epithelial cells. Our findings uncovered that PRMT7-mediated arginine methylation plays critical roles in regulating MAVS-mediated antiviral innate immune responses, and targeting arginine methylation might represent a therapeutic avenue for treating RNA viral infection.

Performance evaluation of the high-throughput quantitative Alinity m Epstein-Barr virus assay.

Epstein-Barr virus (EBV) infection and reactivation are associated with increased risk for post-transplant lymphoproliferative disorders (PTLD) in transplant recipients with the development of PTLD occurring predominantly within a year of transplant. Quantitative PCR for EBV is used to monitor the viral load of EBV with a negative result as a good negative predictor of PTLD. Nucleic acid amplification tests (NAATs) with high sensitivity and specificity are available on fully automated high-throughput instruments to provide accurate quantitation and improve test result turn-around time. This study evaluates the analytical and clinical performance of one such NAAT, the Alinity m EBV assay.

Single-Nucleus and Spatial Transcriptomics Revealing Host Response Differences Triggered by Mutated Virus in Severe Dengue

Dengue virus (DENV) infection causes various disease manifestations ranging from an asymptomatic state to severe, life-threatening dengue. Despite intensive research, the molecular mechanisms underlying the abnormal host responses and severe disease symptoms caused by evolved DENV strains is not fully understood. First, the spatial structure of mutant DENV was compared via in silico molecular modeling analysis. Second, employing single-nucleus and spatial RNA sequencing, we analyzed and verified transcriptome samples in uninfected, mild (NGC group), and severe (N10 group) liver tissues from murine models. In this study, we obtained a cumulatively mutated DENV-2 N10 with enhanced capability of replication and pathogenicity post 10 serial passages in Ifnra−/− mice. This variant caused severe damage in the liver, as compared with other organs. Furthermore, mutated DENV infection elicited stronger responses in hepatocytes. The critical host factor Nrg4 was identified. It dominated mainly via the activation of the NRG/ErbB pathway in mice with severe symptoms. We report on evolved N10 viruses with changes observed in different organisms and tissue. This evolutionary variant results in high replicability, severe pathogenicity, and strong responses in murine. Moreover, the host responses may play a role by activating the NRG/ErbB signaling pathway. Our findings provide a realistic framework for defining disturbed host responses at the animal model level that might be one of the main causes of severe dengue and the potential application value.

Preferences and Feasibility of Long-Acting Technologies for the Treatment of Hepatitis C Virus: A Survey of Patients in Diverse Low- and Middle-Income Countries.

Despite available curative treatments, global rates of hepatitis C virus (HCV) infection persist with significant burden in low- and middle-income countries (LMICs). Long-acting (LA) antiviral products are in development. This study explored the challenges and opportunities in LA-HCV treatment across three LMICs: Egypt, Ethiopia and India. The survey focused on understanding barriers and facilitators to treatment, with emphasis on LA treatment preferences. Four-hundred respondents completed a survey including demographics, HCV treatment history and preferences for injections, implants and microarray patches (MAPs) compared to pills. Overall, 78% of respondents were willing to receive injections, 43% were willing to receive implants and 55% were willing to receive MAPs. Marked heterogeneity in acceptability of non-oral treatments was observed. Among respondents who had not previously received HCV treatment, 94%, 43%, and 75% were willing to receive injections, implants, or MAPs, respectively. In contrast, among those already cured by oral HCV treatment, 61%, 40% and 43% were willing to receive injections, implants or MAPs. Other characteristics associated with willingness to receive an injection included urban residence, younger age, male sex, higher education level and taking pills for any reason (all results p < 0.001). The most common concern for all LA modalities was lack of effectiveness. Prior experience with injection or implant increased willingness to receive any LA modality (p < 0.001). Coupled with a point-of-care HCV diagnostic test, availability of and willingness to receive HCV treatment delivered by a LA formulation could simplify and expand treatment access in LMICs and contribute towards global HCV elimination goals.